The prediction of clinical recurrence is significantly influenced by the transition from pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). ∼16% of patients who achieve pCR may still encounter disease recurrence, whereas 45% of patients with recurrent disease do not. Longitudinal circulating tumor DNA (ctDNA) testing presents a less invasive method for monitoring the response to treatment in early breast cancer (BC) patients undergoing NAC.
This study aimed to determine whether the status and changes in ctDNA can effectively predict the tumor response to NAC and the likelihood of recurrence in patients with early BC.
This was an observational, retrospective, single-center study to investigate whether ctDNA can predict tumor response to NAC and prognosis in patients with breast cancer. Seventy-four patients received standard-of-care NAC, and 4 were treated with adjuvant therapy.
At diagnosis, baseline blood samples were collected from 44 patients and longitudinally during treatment from 34 patients. Reported outcomes included tumor response and progression. The status and dynamics of ctDNA were correlated with pathologic and radiologic outcomes.
Results indicated that 29 patients with triple-negative breast cancer (TNBC) were ctDNA-positive at baseline, and 6 were ctDNA-negative. Of the 29 patients, early ctDNA clearance by week 6 of NAC was observed in 10 patients, weeks 7-16 in 9 patients, clearance post-surgery in 1 patient, and 3 patients remained ctDNA-positive after surgery, Currently, serial ctDNA testing is underway for the remaining 6 patients.
All patients with TNBC who had a radiological complete response (CR) had early ctDNA clearance. After completion of NAC, there was a radiological partial response (PR) in all patients with persistent ctDNA positivity levels. Of the 9 patients with TNBC with undetectable baseline ctDNA, 33% achieved CR, and 43% achieved pathologic CR. Of the 19 patients with TNBC with ctDNA clearance in response to NAC, 89% (17/19) remained ctDNA-negative, with no evidence of disease.
One patient initially cleared their ctDNA on NAC before turning ctDNA-positive 4 weeks prior to radiological recurrence, and another patient with ctDNA clearance on NAC remained ctDNA post-surgery but experienced recurrence. All (n=3) patients with TNBC with persistent ctDNA-positivity levels after curative treatment (NAC and surgery) had disease recurrence. All 6 patients with undetectable baseline ctDNA continued to be ctDNA-negative regardless of their disease status. At diagnosis, 8/9 estrogen receptor (ER)-positive patients were also ctDNA-positive.
Close to 40% of patients who were ER-positive with positive baseline ctDNA had early clearance of ctDNA after NAC. All 3 patients had residual disease on pathology. One-fourth of patients had ctDNA+ after surgery, and neither achieved radiologic CR or pCR. The remaining 3 patients are ongoing NAC.
Monitoring with ctDNA in the early stages of TNBC enables the prediction of tumor response to NAC and the customization of therapeutic regimens.
The persistence of ctDNA can predict early recurrence and help identify patients who may need treatment escalation or enrollment in clinical trials. Despite the limited patient population, the clearance of ctDNA does not serve as a reliable predictor for the response to NAC in ER-positive breast cancer.
Nirogacestat is the only FDA-approved drug indicated for the treatment of desmoid tumors. It is effective across various lines of therapy, including first-line therapy. If adverse events (AEs), such as diarrhea, nasal congestion, and transaminitis, develop, then doses can be interrupted, and supportive care can be given.
Fruquintinib is a selective oral inhibitor of vascular endothelial growth factor receptors (VEGFRs)-1, -2, and -3. It is currently FDA-approved following prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF therapy, and, if RAS wild‑type and medically appropriate, an anti-epidermal growth factor receptor therapy. Based on improved overall survival, it is indicated for a third-line or greater setting for unresectable metastatic colorectal cancer.
Belzutifan is an oral inhibitor of hypoxia-inducible factor 2 alpha and is approved for treating Hippel-Lindau disease and advanced renal cell carcinoma (RCC) after progression on an immune checkpoint inhibitor and a tyrosine kinase inhibitor. In the registrational phase 3 trial for patients with RCC, tumor reduction or stabilization occurred in two-thirds of patients.
There was also an increased objective response rate and duration of response compared to the control arm, where AEs included anemia, hypoxia, and fatigue. Monthly hemoglobin monitoring, self-monitoring of oxygen saturation, and appropriate dose adjustments and interventions will improve patients’ quality of life while taking belzutifan.
Capivasertib and fulvestrant are used as standard treatments for advanced breast cancer with alterations in PIK3CA/AKT1/PTEN. It is considered for use in patients after progression on endocrine therapy plus a CDK 4/6 inhibitor or in later lines of therapy.
This treatment is indicated for cancers with alterations in AKT1/PTEN. Capivasertib and fulvestrant are generally well tolerated in patients with advanced breast cancer, with AEs consisting of diarrhea and rash.
Lorlatinib, a third-generation ALK tyrosine kinase inhibitor that can penetrate the brain, showed enhanced progression-free survival (PFS) and intracranial (IC) activity compared to crizotinib in treatment-naïve patients with advanced ALK-positive non-small cell lung cancer (NSCLC) in the phase 3 CROWN study. The CROWN study’s long-term efficacy and safety results are now reported after a 5-year follow-up.
In total, 296 patients who had not received any prior treatment and had advanced ALK-positive NSCLC were randomly assigned 1:1 to receive lorlatinib 100 mg once daily (n=149) or crizotinib 250 mg twice daily (n=147). In this post hoc analysis, the efficacy outcomes, safety, and biomarker analyses are reported as assessed by the investigators. No formal statistical testing was conducted.
By October 31, 2023, 74 of 149 patients (50%) were still receiving lorlatinib, while 7 of 142 patients (5%) were still using crizotinib. The median duration of follow-up for progression-free survival (PFS) was 60.2 months (95% CI, 57.4-61.6) for lorlatinib and 55.1 months (95% CI, 36.8-62.5) for crizotinib.
The median PFS (95% CI) was not reached (NR) (NR, 64.3-NR) for lorlatinib, versus 9.1 months (95% CI, 7.4-10.9) for crizotinib (hazard ratio [HR], 0.19; 95% CI, 0.13-0.27). The 5-year PFS (95% CI) was 60% (51-68) for lorlatinib and 8% (3-14) for crizotinib.
The median time to IC progression (95% CI) was not reached (NR; NR-NR) for lorlatinib and 16.4 months (95% CI, 12.7-21.9) for crizotinib (hazard ratio [HR], 0.06; 95% CI, 0.03-0.12). In patients without baseline brain metastases in the lorlatinib group, brain progression was observed in 4 of 114 patients, all within the initial 16 months of therapy. Grade 3/4 adverse events (AEs) were reported in 77% of patients receiving lorlatinib and 57% of those on crizotinib.
Treatment-based AEs led to treatment discontinuation in 5% and 6% of patients in the lorlatinib and crizotinib groups, respectively. The safety profile remained consistent with previous analyses, and no new ALK mutations were detected in circulating tumor DNA after lorlatinib treatment (n=31).
After a 5-year follow-up, the lorlatinib arm had not reached the median PFS, setting a record for the longest PFS reported in advanced NSCLC. These results, combined with the absence of any new safety issues, demonstrate the extraordinary improvement in outcomes for individuals with advanced ALK-positive NSCLC.
Source: Solomon BJ, Liu G, Felip E, et al. Lorlatinib versus crizotinib in treatment-naïve patients with advanced ALK+ non-small cell lung cancer: 5-year progression-free survival and safety from the CROWN study. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; May 31, 2024: abstract LBA8503.
The EVOKE-01 study, a phase 3 trial with an open-label design, compared sacituzumab govitecan (SG) to docetaxel as a standard-of-care treatment for metastatic non–small cell lung cancer (mNSCLC) patients who had experienced disease progression following platinum-based chemotherapy, anti–programmed death-ligand 1 (PD-L1) therapy, and targeted treatment for actionable genomic alterations (AGAs). These are the primary analysis results.
Patients were randomly assigned 1:1 and stratified by histology, superior response to the previous anti–PD-L1-containing regimen, and whether AGA treatment was received to either SG (one 10 mg/kg intravenous [IV] infusion on days 1 and 8) or docetaxel (one 75 mg/m2 IV infusion on day 1) in 21-day cycles.
The primary focus of the study was overall survival (OS), while key secondary endpoints included investigator-assessed progression-free survival (PFS), objective response rate, patient-reported symptom assessment, and safety.
In the intent-to-treat population, which consisted of 299 patients in the SG group and 304 patients in the docetaxel group, 55.4% had received 1 previous line of therapy. The median follow-up period was 12.7 months, ranging from 6 to 24 months.
Although the primary endpoint was not achieved, OS for SG improved compared to docetaxel, with a median OS of 11.1 months versus 9.8 months, respectively (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.68-1.04], 1-sided; P=.0534). This trend was consistent across squamous and nonsquamous histologies.
The median PFS was 4.1 months for SG and 3.9 months for docetaxel (HR, 0.92; 95% CI, 0.77-1.11). An OS benefit was noted for SG in comparison to docetaxel among patients with mNSCLC who were nonresponsive to the last anti–PD-L1-containing regimen, showing a 3.5-month median OS increase and an HR of 0.75 (95% CI, 0.58-0.97), which was consistent across different histologies.
The discontinuation rate due to treatment-related adverse events (TRAEs) was 6.8% for SG and 14.2% for docetaxel, respectively, with TRAEs leading to death in 1.4% and 1.0% of patients, respectively.
Despite not reaching statistical significance, SG improved OS compared to docetaxel, which was consistent across different histologies. A clinically significant enhancement in OS was observed in patients with mNSCLC who did not respond to the last anti–PD-L1-containing regimen.
SG demonstrated better tolerability than docetaxel and maintained its established safety profile, with no new safety concerns identified.
Source: Paz-Ares LG, Juan-Vidal O, Mountzios GS, et al. Sacituzumab govitecan (SG) versus docetaxel (doc) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) previously treated with platinum (PT)-based chemotherapy (chemo) and PD(L)-1 inhibitors (IO): primary results from the phase 3 EVOKE-01 study. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; May 31, 2024: abstract LBA8500.
The bispecific antibody, ivonescimab (AK112/SMT112), acts as an anti–programmed death-1 (PD-1)/vascular endothelial growth factor (VEGF) agent. Promising results from phase 1/2 clinical trials have indicated its potential efficacy in patients with non-small cell lung cancer (NSCLC) accompanied by epidermal growth factor receptor (EGFR) mutations who had previously undergone unsuccessful EGFR-tyrosine kinase inhibitor (TKI) therapies.
This phase 3 study was conducted to investigate further and confirm the effectiveness and safety of combining ivonescimab with chemotherapy instead of chemotherapy alone. This study enrolled patients who were randomly assigned 1:1 to ivonescimab (20 mg/kg) plus pemetrexed (500 mg/m2) and carboplatin or placebo in combination with chemotherapy.
This treatment was administered once every 3 weeks for 4 cycles. Stratification was done based on the use of third-generation EGFR-TKI (received/not received) and the presence or absence of brain metastases. Following the initial cycles, patients underwent maintenance therapy with either ivonescimab and pemetrexed or placebo and pemetrexed.
The study’s main objective was to evaluate progression-free survival (PFS) in the intent-to-treat population. An independent radiographic review committee (IRRC) conducted this assessment using RECIST (version 1.1) criteria.
A total of 322 patients were randomly assigned to either the ivonescimab plus chemotherapy arm (161 patients) or the placebo plus chemotherapy arm (161 patients). The percentage of patients who had received third-generation EGFR-TKIs treatment was 86.3% versus 85.1%, respectively, and the percentage of patients with brain metastases was 21.7% versus 23.0%, respectively.
As of March 10, 2023, the median follow-up time was 7.89 months. PFS was significantly more effective in the ivonescimab plus chemotherapy arm (hazard ratio [HR], 0.46 [0.34, 0.62]; P<.0001).
The median PFS (95% confidence interval) by IRRC was 7.06 months (5.85, 8.74) in the ivonescimab arm compared to 4.80 months (4.21, 5.55) in the chemotherapy arm. Subgroup analyses indicated that PFS benefit favored patients receiving ivonescimab over placebo in almost all subgroups, including those who progressed on third-generation EGFR-TKIs therapy, those with brain metastases, those with EGFR mutation of deletion 19 (HR, 0.48; 0.32-0.73), and patients who were T790M mutation-positive.
The objective response rates were 50.6% and 35.4% for the 2 groups. Grade ≥3 treatment-emergent adverse events (TEAEs) were observed in 99 (61.5%) patients receiving ivonescimab plus chemotherapy versus 79 (49.1%) patients receiving placebo plus chemotherapy. The most common grade ≥3 TEAEs were adverse events (AEs) related to chemotherapy.
Grade ≥3 immune-related AEs were reported in 10 (6.2%) patients versus 4 (2.5%) patients, respectively. Additionally, grade ≥3 AEs related to VEGF blocking occurred in 5 patients (3.1%) versus 4 patients (2.5%), respectively.
Ivonescimab, in combination with chemotherapy, demonstrated a notable enhancement in PFS among patients who had previously experienced treatment failure with EGFR-TKIs. Importantly, this treatment approach maintained a manageable safety profile.
Source: Zhang L, Fang W, Zhao Y, et al. Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor treatment (HARMONi-A): a randomized, double-blind, multi-center, phase 3 trial. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; May 31, 2024: abstract 8508.
The proliferation of trials examining bispecific antibodies for treating diffuse large B-cell lymphoma (DLBCL) is a significant development. However, geographical barriers impede the universal availability of these trials.
This study delves into the crucial issue of disparities in geographical and racial access to bispecific antibody trials for DLBCL, underscoring its potential impact on healthcare policies.
The search for clinical trials related to DLBCL and bispecific antibodies was conducted on ClinicalTrials.gov, ensuring a comprehensive analysis. This study encompassed 13 of 51 clinical trials with ≥1 available sites in the United States. The 2020 US Census Bureau data were used to gather information on race and ethnicity, further enhancing the depth of the research. The statistical analysis was performed using the IBM® SPSS® Statistics Server (Version 26).
Most of the trials conducted were phase 1 (62%), followed by phase 2 (23%) and phase 2/3 (15%). In total, 885 participants were enrolled or expected to enroll in these clinical trials. Most of the trials (69%) were exclusively open in the United States, while 31% were open in the United States and other countries.
The pharmaceutical industry funded 62% of the trials. There were 50 unique study sites spread across 24 states, with an average of 2.4 trials per state and 9.9 sites per trial. There were study sites established across 24 different states.
The distribution of trials across different states and regions shows the geographical disparities in access to bispecific antibody trials for DLBCL. The Midwestern states had the highest percentage of trials, 28%, followed by the Southern states, 26%, the Northeastern states, 24%, and the Western states, 22%.
California emerged as a significant hub with the highest number of study locations, 10, and the highest number of open studies, also 10. Notably, 27 states did not have any ongoing trials for bispecific antibodies, highlighting the extent of the disparities.
Three were in the Northeast (Maine, Rhode Island, and Vermont), 5 in the Midwest (Illinois, Indiana, Nebraska, North Dakota, and South Dakota), 8 in the South (Delaware, Virginia, District of Columbia, West Virginia, Mississippi, Arkansas, Louisiana, and Oklahoma), and 11 in the West (Arizona, Colorado, Idaho, New Mexico, Montana, Nevada, Wyoming, Alaska, Hawaii, Oregon, and Washington).
According to data from the US Census Bureau, 20% of African Americans (8,349,699 of 41,104,200) resided in a county where a bispecific antibodies trial was being conducted. Of all the states, only 5 had ≥50% of their African American population living in a county with an ongoing bispecific antibodies trial. Additionally, 7 states (29%) had 30% to 49.9% of African American residents living in such counties.
Surprisingly, 5 states had less than 10% of their African American population residing in a county with an open bispecific antibodies trial. It is noteworthy that of the 10 states with the highest proportion of African American residents (range, 18.6%-41.4%), 9 either lacked any clinical trial sites (5 states) or had only 1 (4 states).
Access to bispecific antibody trials for DLBCL is marked by significant disparities, particularly in terms of geographic and racial factors. Efforts should be directed toward formulating strategies that effectively address the root causes of these disparities and aim to enhance the overall accessibility to these trials.
Source: Shahzad M, Khalid MF, Park R, et al. Geographic and racial disparities in bi-specific antibodies trials access for diffuse large B-cell lymphoma. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 1, 2024: abstract 1525.
Prostate cancer ranks as the second most common cause of cancer-related deaths among men in the United States. Aggressive forms of this cancer are linked to mutations in homologous recombination repair (HRRm) genes. The FDA has approved poly (ADP-ribose) polymerase (PARP) inhibitors such as olaparib, rucaparib, niraparib, and talazoparib for treating patients with metastatic castration-resistant prostate cancer (mCRPC) associated with HRRm.
Although previous studies have demonstrated that PARP inhibition provides the most significant benefits to patients with HRRm, current data suggest that the responses in HRR genes other than BRCA1/2 and ATM appear to be less effective.
In this retrospective study, the electronic health record was utilized to identify adult patients who were diagnosed with prostate cancer and received treatment at Avera Cancer Institute between January 1, 2018, and December 31, 2022.
These patients underwent somatic and/or germline genetic testing, and the results were reviewed for the presence of pathogenic HRRm genes, including BRCA1, BRCA2, ATM, ATR, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C.
Additionally, the patients’ treatment histories were examined to identify the use of PARP inhibition. Information considering the PARP inhibitor received, the duration of treatment, and the biochemical response regarding a decline in prostate-specific antigen levels during therapy was collected.
This analysis included 191 patients. Of these patients, 46% had germline-only testing, 16% had somatic-only testing, and 38% had both germline and somatic testing. A total of 45 patients had HRRm, of which 22 were somatic and 33 were germline.
The average patient age at the time of testing was 70 years, and in patients who received PARP inhibitor therapy, the average age at testing was 73 years. Thirteen patients in this cohort received treatment with a PARP inhibitor. Twelve of these patients received treatment with olaparib monotherapy, and 1 patient received olaparib in combination with abiraterone.
The average progression-free survival (PFS) was 26 months, and the median PFS was 11 months. Four patients were biochemical nonresponders, with an average PFS of 8 months, compared with 33 months for the 9 biochemical responders (P=.04). In nonresponders, the detected gene alterations included germline BRCA1 (n=1), germline CHEK2 (n=2), and somatic ATM (n=1). Germline alterations present in responders included BRCA2 (n=7) and PALB2 (n=2).
The patients diagnosed with HRRm and subsequently treated with a PARP inhibitor exhibited comparable responses to previously reported data. Specifically, the group with BRCA2 mutations displayed the most favorable response, followed by tumors with PALB2 mutations. The overall number of patients with HRRm who received PARP inhibitor treatment was lower than anticipated, which necessitates further investigation. The introduction of new FDA-approved PARP inhibitors in combination with next-generation hormonal agents in the first-line mCRPC setting is expected to enhance the utilization of PARP inhibitors.
Gathering additional outcomes data for individual HRR genes is imperative to enhance patient selection and outcomes and minimize unnecessary toxicity associated with PARP inhibitor therapy.
Source: Alstyne TV, Corsini C, Owen P, et al. Utilization of genetic and genomic data and correlation to outcomes of treatment with PARP inhibitors in advanced or metastatic castrate-resistant prostate cancer. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 1, 2024: abstract e17034.
Patients diagnosed with cancer who have a lower income are found to have a 30% reduced likelihood of taking part in clinical trials. Lower-income individuals encounter direct and indirect expenses that can hinder their participation in such trials.
Nevertheless, a comprehensive analysis of various factors, such as behavioral patterns, access to information, insurance coverage, and regional characteristics, that may contribute to this inequality has not yet been carried out.
This analysis aimed to create and validate a model that can effectively identify socioeconomically vulnerable patients at a higher risk of not participating in clinical trials.
Data were utilized from the Health Information National Trends Survey (HINTS), a nationwide survey that focuses on individuals’ knowledge, attitudes, and utilization of health-related information. This analysis involved examining the HINTS survey databases, specifically questions related to the involvement of cancer patients in clinical trials during the 2014, 2017, and 2020 survey years.
Twenty-one diverse factors were explored, including demographic, socioeconomic, behavioral, geographic, and health-related information. To predict the likelihood of clinical trial participation, a risk model was developed using the best subset selection technique with k-fold cross-validation on a random set of 60% of participants. The accuracy of the derived model was then assessed on the remaining 40% of participants using logistic regression.
A total of 1023 participants with household incomes <$75,000 were examined. A model comprising 5 variables was identified in the training dataset, which consisted of 614 participants. Non-Hispanic White patients and patients without a college education, with high levels of distrust, with high levels of anxiety or depression, and from non-urban areas were all at lower risk of trial participation.
The adverse risk factors for all individuals were summed up; a risk score with 4 levels was constructed based on distribution quartiles. In the validation cohort consisting of 409 individuals, it was observed that for every increment in the level of adverse risk factors, there was a 73% increase in the likelihood of nonparticipation in the trials (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.19-2.53; P=.004), indicating successful validation of the model.
The trial participation rates among individuals experienced a steady decline from 18.6% for those with 0 or 1 adverse risk factors to 2.8% for those with 4 or 5 factors. Individuals with 4 or 5 risk factors were >7 times more likely not to participate in a clinical trial (OR, 7.89; 95% CI, 3.21-19.36; P<.001).
A 5-variable risk model was developed and validated to identify many lower-income individuals with a lower likelihood of participating in trials. Interestingly, psychosocial variables have been revealed as key predictors of reduced trial participation for the first time.
These discoveries could facilitate the early detection of patients in need of additional support to navigate the treatment trial decision-making process, thereby promoting more equitable participation in trials for all patients.
Source: Szarama K, Unger JM. Cancer clinical trial participation in socioeconomically vulnerable patients: a risk model to aid in targeted interventions. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 1, 2024: abstract 1529.
During this session, panelists Monica Bertagnolli, MD, FACS, FASCO, director of the National Institutes of Health (NIH), and Dr W Kimryn Rathmell, MD, PhD, FASCO, director of the National Cancer Institute (NCI), discussed patients’ access and equity to clinical trials. They discussed that we need to integrate learning with care, and they are developing infrastructures to bring “big data” together.
Dr Bertagnolli unveiled a groundbreaking plan to standardize electronic health record data capture and storage, a move that could revolutionize data collection and analysis. She cited the SEER registry as an example, revealing a 3-year gap between data collection and receipt, and the labor-intensive nature of the process. According to Dr Bertagnolli, standardized data models could eliminate these challenges, marking a significant step forward in data management.
Dr Bertagnolli also shared a promising development from the Centers for Medicare & Medicaid Services, the new Enhancing Oncology Model. This innovative model is designed to foster better care coordination in oncology treatment, ultimately improving the quality of care for cancer patients covered by Medicare fee-for-service, while also reducing program expenditures.
In terms of bringing new investigators into research, Dr Rathmell indicated they are investing in young people and that getting their first grant is important. This was followed by a discussion that there is a workforce issue, which is whether junior investigators will stay in academia. They stated that messaging is important to counteract the negativity around academia found on social media.
Dr Rathmell further indicated that the focus should remain on how exciting this field is and stressed the importance of supporting trainees in pursuing a career in their chosen environment to help ensure that they find the right path. Dr Bertagnolli further added that their partnership with academic institutions is important to nurture young investigators, especially through training awards.
Moderator: Angela DeMichele, MD, MSCE, FASCO, University of Pennsylvania
Panelists: Monica Bertagnolli, MD, FACS, FASCO, National Institutes of Health; W. Kimryn Rathmell, MD, PhD, FASCO, National Cancer Institute
Colorectal cancer disparities pose significant challenges for marginalized communities of color in the United States, where obstacles to screening participation can contribute to late-stage diagnoses and unfavorable outcomes.
Despite the efforts of patient navigators (PN) at the Montefiore Einstein Comprehensive Cancer Center in New York City, which serves an ethnically marginalized and socioeconomically disadvantaged population, 59% of 6613 patients either canceled or failed to attend their scheduled colonoscopy appointments in 2022.
Although the PN’s re-engagement initiatives resulted in only 21% of patients successfully completing their colonoscopies, recognizing the potential of conversational, artificial intelligence (AI)-driven applications in healthcare to alleviate the strain on an overburdened workforce is an important undertaking.
Montefiore Einstein Cancer Center explored the implementation of an AI-based, virtual PN, MyEleanor, as part of a quality improvement (QI) project aimed at enhancing colorectal cancer screening. This QI project utilized MyEleanor from April 2023 to December 2023 to successfully re-engage 2400 nonadherent patients with colonoscopy appointments between 2022 and 2023, demonstrating the promising potential of this technology.
MyEleanor, unlike human PNs, has the unique capability to contact patients directly, facilitating discussions about rescheduling and assessing the barriers preventing them from scheduling their appointments. It also offers live transfers to clinical staff for rescheduling purposes and provides reminder calls regarding the procedure preparation, all of which contribute to its effectiveness in enhancing colorectal cancer screening.
The measurable outcomes of this project included the level of engagement with MyEleanor through identity confirmation, the number of accepted live transfers (actionable), the rate of colonoscopy completion, and patient volume. Additionally, the project examined the barriers to care and the predictors of actionable engagement.
During a period of over 8 months, 57% (1368 of 2400) of patients interacted with MyEleanor, and 58% (789) of this group, or 33% overall, agreed to the live transfer. The completion rate for patients who missed their initial appointment nearly doubled from 10% to 19% between 2022 and 2023 (pre- to post-MyEleanor).
Engaged patients, on average, were aged 56.7 years (range, 41 to 79 years), were mostly female (66%), Hispanic (41%), Black (33%), English (73%), or Spanish (25%). In total, 52% reported facing barriers to screening. The main obstacles included lack of perceived need (36%), time constraints (36%), MD referral (33%), medical mistrust (32%), concerns about test results (28%), and cost (27%).
This project showcases the significant potential of an AI patient navigator in addressing patient attrition issues that may contribute to colon cancer disparities while enhancing patient volume. The upcoming stage of the project will assess the effects on patient prep adherence, staff workload, and revenue.
Source: Moadel AB, Galeano D, Bakalar J, et al. AI virtual patient navigation to promote re-engagement of U.S. inner city patients nonadherent with colonoscopy appointments: a quality improvement initiative. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 1, 2024: abstract 100.
The standard first-line treatment for human receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer involves a combination of CDK4/6 inhibitors and endocrine therapy (ET). Although disease progression is common in patients with advanced breast cancer, the most effective treatment for those who experience progression on a CDK4/6 inhibitor plus ET is still uncertain.
Real-world evidence indicates that using abemaciclib, an oral CDK4/6 inhibitor with greater selectivity for CDK4, after disease progression on a previous CDK4/6 inhibitor can extend progression-free survival (PFS) in advanced breast cancer. However, other trials with other CDK4/6 inhibitors have produced mixed results.
This study presents the primary outcome analysis of the phase 3 postMONARCH trial (NCT05169567), which evaluated fulvestrant plus abemaciclib or placebo in patients with HR-positive, HER2-negative advanced breast cancer after disease progression on a prior CDK4/6 inhibitor plus ET. The postMONARCH trial was a global, double-blind, placebo-controlled study where patients were randomized 1:1 to receive either abemaciclib plus fulvestrant or placebo plus fulvestrant.
Patients eligible for the study had experienced disease progression on a CDK4/6 inhibitor plus aromatase inhibitor as initial therapy for advanced breast cancer or had a relapse on/after a CDK4/6 inhibitor plus endocrine therapy as adjuvant treatment for early breast cancer.
Only patients with no prior treatment for advanced breast cancer could participate. The study’s primary endpoint was investigator-assessed PFS, and secondary endpoints included PFS assessed by a blinded independent central review (BICR), overall survival, objective response rate (ORR), and safety.
With an assumed hazard ratio (HR) of 0.7, the study had ~80% power to detect superiority for abemaciclib while maintaining a cumulative 2-sided type I error of 0.05. The Kaplan-Meier method was utilized to estimate progression-free survival curves, and the treatment effect was estimated using a stratified Cox proportional hazard model.
A total of 368 patients were randomly assigned to receive either abemaciclib plus fulvestrant (n=182) or placebo plus fulvestrant (n=186). Prior use of a CDK4/6 inhibitor included palbociclib (59%), ribociclib (33%), and abemaciclib (8%) in the abemaciclib plus fulvestrant arm and 59%, 33%, and 8%, respectively, in the placebo plus fulvestrant arm.
The interim analysis showed that the study met the predetermined criteria for significantly improved investigator-assessed PFS with abemaciclib plus fulvestrant compared to placebo plus fulvestrant (HR, 0.66; 95% confidence interval [CI], 0.48-0.91; P=.01).
In the primary analysis (HR, 0.73; 95% CI, 0.57-0.95), with PFS rates at 6 months of 50% versus 37% for the abemaciclib and placebo groups, respectively. The ORR was higher with abemaciclib compared to placebo, 17% versus 7% in patients with measurable disease. According to BICR, PFS also showed improvement (HR, 0.55; 95% CI, 0.39-0.77). Safety was consistent with what has been previously reported with abemaciclib, and the discontinuation rate due to adverse events was low (6%).
The combination of abemaciclib and fulvestrant exhibited a notable enhancement in PFS among patients with HR-positive, HER2-negative advanced breast cancer after disease progression on a CDK 4/6 inhibitor.
This combination also consistently improved across key secondary efficacy endpoints, including PFS by BICR and ORR, without any new safety signals in this patient population. This study’s results indicate that patients benefit from continued CDK4/6 inhibition with abemaciclib plus fulvestrant following progression on a CDK 4/6 inhibitor.
Source: Kalinsky K, Bianchini G, Hamilton EP, et al. Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 1, 2024: abstract LBA1001.
In this presentation, Liz Salmi presented her perspective as a patient with brain cancer with access to her electronic medical records (EMR). She described that upon receiving her test results in her EMR, she would review her test results and search on the internet for explanations on topics or categories where she had questions.
When she had to change healthcare providers, she requested medical records consisting of 4839 pages. In those records, she found notes from her doctors that she had never seen before, which would have been helpful in answering her questions about her medical tests and diagnosis. She then described how, based on this experience, she became an advocate for transparency and access to medical information.
She then teamed up with researchers at Beth Israel Deaconess Medical Center, where they encouraged clinicians to share notes with patients. They founded Open Notes, which lets patients easily read progress notes. Since 2012, there have been >120 published studies and commentaries on this subject.
Studies have found that when patients read their notes, they feel more engaged with their care, remember more from medical visits, and mutual trust between doctors and patients increases. By 2020, >260 health systems around the United States proactively offered patients access to doctors’ notes.
In 2021, the 21st Century Cures Act mandated that all federally funded research must be open access and that patient health data must be delivered directly to patients without charge or delay via cell phones, computers, and mobile applications.
A multi-site survey across 4 medical centers was conducted to evaluate patients’ views about accessing their medical test results. It was found that 96% of non-cancer-specific patients wanted to see their test results immediately. This study also found that 8% of patients with abnormal test results worry more, and 46% worry less when they receive their results through EMRs.
Ms Salmi concluded that transparency increased trust between clinicians and patients and that patients want to view their medical information. She suggested that healthcare providers offer anticipatory guidance when ordering medical testing.
Source: Salmi L. When bad news comes through the portal: from a patient’s perspective. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 2, 2024.
Circulating tumor DNA (ctDNA) has the potential to address the constraints associated with tissue biopsy in individuals diagnosed with metastatic breast cancer (mBC). Unlike tissue biopsy, which offers a single snapshot of the tumor’s molecular characteristics at a specific location and moment, ctDNA presents a more comprehensive view of the tumor genome. Serial liquid biopsies can be conveniently collected to monitor clinical responses and the development of resistance over time.
The Individualized Molecular Analyses Guide Efforts in Breast Cancer (IMAGE II) study focuses on assessing the effectiveness of tissue biopsy and serial liquid biopsy techniques in profiling tumor genomics in mBC.
IMAGE II (NCT02965755) is a prospective, multicenter trial designed to assess the clinical effectiveness of liquid biopsy compared with tissue biopsy. Participants included individuals with mBC of any subtype who showed progression necessitating a change in therapy.
As per standard care, tissue biopsy sequencing was mandatory unless a biopsy was not feasible. At the time of enrollment, Foundation Medicine obtained baseline plasma samples for tissue-agnostic comprehensive genomic profiling (CGP).
The results of both liquid biopsy and tissue biopsy sequencing were promptly reviewed by the Johns Hopkins Molecular Tumor Board for treatment recommendations. Serial liquid biopsy samples were collected 1 to 2 weeks after starting the next line of therapy, at the first restaging, and at progression. This analysis reports on the data obtained at enrollment, with the results of serial liquid biopsy samples to be disclosed later.
A total of 199 patients were enrolled, 194 of whom were women (median age, 57 years; age range, 27-86 years). There were 140 hormone receptor (HR)-positive–human epidermal growth factor receptor 2 (HER2)-negative, 4 HR-negative–HER2-positive, 20 HR-positive–HER2-positive, and 35 triple-negative breast cancer cases. Metastases were detected solely in the bone in 19 patients, while in 99, they involved the lung. Additionally, metastases were observed in the liver in 97 patients and the brain in 14 patients.
The median prior lines of metastatic therapy were 2, with 22.1% of patients having been on ≥4 therapies, including antibody–drug conjugates (14 patients), immunotherapy (2), cytotoxic chemotherapy (74), endocrine therapy (88), and targeted therapy (12). At the time of enrollment, 9 patients were newly diagnosed with mBC. Overall, 55% underwent tissue biopsy sequencing.
In the CGP results obtained from 190 patients, the genes that exhibited the highest frequency of alterations were TP53 (90 patients), PIK3CA (63 patients), and ESR1 (54 patients). This study revealed copy number amplifications in FGFR1 (21 patients) and FGFR3 (12 patients) and copy number losses in PTEN (3 patients).
Of 87 individuals whose initial liquid biopsy was analyzed using FoundationOne Liquid CDx to calculate ctDNA tumor fraction, 69 (79.3%) patients exhibited detectable ctDNA tumor fraction. Additionally, ≥1% ctDNA tumor fraction was found in 69% of patients.
The high rate of ctDNA tumor fraction identification in patients suffering from mBC highlights the significance of utilizing liquid biopsy for CGP and enables the detection of multiple alteration classes across different mBC subtypes and metastatic sites.
Source: Linville LM, Canzoniero JV, Too F, et al. Utility of circulating tumor DNA (ctDNA) to inform treatment of patients with metastatic breast cancer. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 2, 2024: abstract 1042.
The utilization of triplet or quadruplet therapies as a first-line treatment for multiple myeloma necessitates the exploration of novel combinations at first relapse. This is where the potential of belantamab mafodotin (belamaf) combinations becomes clinically relevant.
In the DREAMM-7 study, the combination of belamaf, bortezomib, and dexamethasone demonstrated a significant improvement in progression-free survival (PFS) and a notable trend towards enhanced overall survival (OS) compared to the combination of daratumumab, bortezomib, and dexamethasone (daratumumab-Vd) in patients who had received ≥1 prior therapy.
Findings from the DREAMM-8 trial (NCT04484623) are reported, which investigated a different belamaf combination (BPd) and successfully achieved its primary objective of demonstrating improved PFS, as assessed by an independent review committee, during a prespecified interim analysis.
DREAMM-8 is an open-label, randomized phase 3 clinical trial that takes place at multiple centers. It aims to assess the effectiveness and safety of BPd versus PVd in patients with relapsed refractory multiple myeloma (RRMM) who have undergone ≥1 prior line of therapy, including lenalidomide. Patients were assigned randomly in a 1:1 ratio to either BPd-based or PVd-based treatment regimens.
In total, 155 patients were randomly assigned to receive BPd, and 147 patients were assigned to PVd. The median follow-up period was 21.8 months (range, 0.03-39.23). The median PFS (95% confidence interval [CI]) was not reached (NR, 20.6-NR) with BPd compared to 12.7 months (9.1-18.5) with PVd (hazard ratio [HR], 0.52; 95% CI, 0.37-0.73; P<.001).
The 12-month PFS rate (95% CI) was 71% (63%-78%) with BPd versus 51% (42%-60%) with PVd. There was a positive trend favoring BPd for OS (HR, 0.77; 95% CI, 0.53-1.14), with ongoing follow-up for OS. Adverse events (AEs) were reported in over 99% and 96% of patients in the BPd and PVd arms, respectively. AEs were generally manageable and consistent with the known safety profile of the individual agents.
The DREAMM-8 trial found a statistically significant and clinically relevant PFS advantage with BPd compared to PVd in patients with RRMM who had received ≥1 line of treatment.
BPd treatment also resulted in more profound and longer-lasting responses, displayed a promising OS trend, and exhibited a manageable safety profile.
Source: Trudel S, Beksac M, Pour L, et al. Results from the randomized phase 3 DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM). Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 2, 2024: abstract LBA105.
Epidermal growth factor receptor (EGFR) mutations are found in nearly one-third of patients with unresectable, stage III non-small cell lung cancer (NSCLC). The standard of care for patients who do not experience progression after concurrent chemoradiotherapy (cCRT) is consolidation durvalumab.
However, the effectiveness of consolidation immunotherapy, specifically for EGFR mutation (EGFRm) NSCLC, is still uncertain due to limited available data. Osimertinib (osi), a third-generation central nervous system-active, EGFR-tyrosine kinase inhibitor (TKI), is recommended for advanced/metastatic EGFRm NSCLC and as adjuvant therapy for resectable EGFRm NSCLC.
Consolidation durvalumab is the standard of care in unresectable stage III NSCLC following CRT without progression. However, the benefit of consolidation durvalumab in EGFRm NSCLC is not certain based on the subgroup analysis from the PACIFIC study.
The efficacy of EGFR-TKIs is supported by the phase 2 RECEL study and real-world data. However, prospective phase 3 studies are needed, and no approved targeted therapies are available for unresectable stage III EGFRm NSCLC.
The primary results are reported from the global, double-blind, placebo-controlled phase 3 LAURA study (NCT03521154), which evaluated the efficacy and safety of osi in unresectable stage III EGFRm NSCLC patients without progression after definitive CRT (dCRT).
Patients who met the eligibility criteria, which included being aged ≥18 years (≥20 years in Japan), having a World Health Organization performance status of 0 or 1, and having unresectable stage III EGFRm (Ex19del/L858R) NSCLC, were enrolled in the study.
The patients were stratified based on the type of CRT received (cCRT vs sequential, the stage of their disease (IIIA vs IIIB/IIIC), and their nationality (Chinese vs non-Chinese).
They were then randomly assigned in a 2:1 ratio to receive either osi 80 mg or placebo once daily until disease progression or discontinuation, as confirmed by a blinded independent central review. Imaging, including brain magnetic resonance imaging, was required at baseline, every 8 weeks up to week 48, and then every 12 weeks until disease progression, as determined by the central review.
The study’s primary endpoint was progression-free survival (PFS), which was assessed by blinded independent central review (BICR) using RECIST (version 1.1) criteria. Secondary endpoints included overall survival (OS) and safety.
A total of 216 participants were randomly assigned to 2 treatment groups: osi, with 143 patients, and placebo (PBO), with 73 patients. The baseline characteristics were generally similar between the osi and PBO groups. The results showed that osi significantly improved PFS compared to PBO, as assessed by BICR. The median PFS was 39.1 months (95% confidence interval [CI], 31.5, not estimable) for osi compared to 5.6 months (95% CI: 3.7, 7.4) for PBO (hazard ratio [HR], 0.16; 95% CI, 0.10-0.24; P<.001. The interim OS analysis (20% maturity) indicated a trend in favor of osi, although not statistically significant (HR, 0.81; 95% CI, 0.42-1.56; P=.530.
Notably, 81% of participants in the PBO arm received osi after disease progression. Adverse events (AEs) were reported in a higher percentage of participants in the osi group compared to the PBO group (98% versus 88%, respectively). Grade 3 or higher AEs were also more common in the osi group (35%) compared to the PBO group (12%).
Osi, after dCRT, showed a significant and clinically meaningful improvement in PFS for unresectable stage III EGFRm NSCLC., There were no unexpected safety signals observed during the study. These findings firmly establish osi as the new standard of care for EGFRm NSCLC in this specific setting.
Source: Ramalingam SS, Kato T, Dong X, et al. Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: primary results of the phase 3 LAURA study. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 2, 2024: abstract LBA4.
TROP2, also known as trophoblast cell surface antigen 2, exhibits high expression levels in triple-negative breast cancer (TNBC) and is correlated with poorer survival outcomes. Sacituzumab irinotecan (SKB264/MK-2870) is an antibody–drug conjugate targeting TROP2, which utilizes a unique linker to attach a belotecan-derivative topoisomerase I inhibitor as the payload.
This study presents the findings from a phase 3 clinical trial (OptiTROP-Breast01, NCT05347134) that evaluated the efficacy and safety of sacituzumab tirumotecan in patients with advanced TNBC.
In this phase 3 randomized trial, SKB264 was compared with the chemotherapy choices of eribulin, vinorelbine, capecitabine, or gemcitabine as selected by physicians for patients with locally recurrent or metastatic TNBC (mTNBC) who had undergone ≥2 prior treatments, including ≥1 for metastatic disease. The primary endpoint was progression-free survival (PFS) determined by blinded independent central review (BICR).
This study included 263 patients, 130 of whom received SKB264 and 133 of whom received chemotherapy. The primary endpoint of PFS was achieved based on an interim analysis conducted on June 21, 2023. As assessed by BICR, the median PFS was 5.7 months (95% CI, 4.3-7.2) for patients receiving SKB264 and 2.3 months (95% CI, 1.6-2.7) for those receiving chemotherapy.
In the first planned interim analysis for overall survival (OS), the median follow-up was 10.4 months, and the results showed a statistically significant advantage for SKB264 compared with chemotherapy (hazard ratio, 0.53; 95% CI, 0.36-0.78; P=.0005). The most common grade ≥3 treatment-related adverse events observed were neutrophil count decreased (32.3% with SKB264 vs 47.0% with chemotherapy), anemia (27.7% with SKB264 vs 6.1% with chemotherapy), and white blood cell count decreased (25.4% with SKB264 vs 36.4% with chemotherapy).
Sacituzumab tirumotecan monotherapy exhibited notable improvements in PFS and OS compared with chemotherapy in patients with heavily pretreated advanced TNBC and limited treatment alternatives. Furthermore, it maintained a manageable safety profile.
Source: Xu B, Yin Y, Fan Y, et al. Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): results from the phase III OptiTROP-Breast01 study. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 2, 2024: abstract 104.
Despite recommendations, genetic testing for advanced prostate cancer (PCa) is not widely used and may not be readily accepted by patients. This analysis investigated the attitudes and decisional conflicts surrounding genetic testing and the differences between White and non-White patients.
This prospective single-institution study included patients with N1 or M1 PCa who had not yet completed genetic testing. To assess attitudes toward genetic testing, including a validated assessment of decisional conflicts, patients were given a 24-question survey using a Likert scale of 0 (strongly agree) to 4 (strongly disagree).
Scores and subscores of decisional conflicts (range, 0-100; 100 = highest decisional conflicts) were calculated from subsets of survey responses, and self-identified race was obtained from the electronic medical record. Two-group comparisons between White and non-White patients and between individuals who completed genetic testing and those who did not were conducted.
Of 42 enrolled patients (21 White, 17 Black, 1 Asian, 3 declined), 52.4% completed genetic testing. Non-White patients demonstrated higher levels of worry regarding the privacy of test results (mean, 1.72 vs 2.95; P=.002), the potential misuse of test results for non-healthcare reasons (1.78 vs 3.00; P=.003), and the experimentation with unproven treatments (1.72 vs 2.67; P=.01) compared with White patients. Compared with White patients, non-White patients felt more external pressure in decision-making (0.67 vs 0.29; P=.04).
There were no significant differences in completion of testing, decisional conflicts, or any subscore between racial groups. Patients who completed the testing showed a higher likelihood of knowing the available options (0.73 vs 1.25; P=.05), understanding the benefits of each option (0.77 vs 1.30; P=.04), being informed about the risks and side effects of each option (0.95 vs 1.50; P=.05), being clear on which benefits mattered most to them (0.73 vs 1.37; P=.02), and being decisive about the best choice for themselves (0.73 vs 1.35; P=.02).
The decisional conflicts score was significantly elevated in patients who did not finish the testing (28.59 vs 18.11; P=.03), as were the uncertainty (31.25 vs 19.32; P=.02) and informed (31.25 vs 20.45; P=.03) subscores. There were no differences in values, clarity, support, or effective decision subscores.
The study revealed that non-White patients exhibited higher levels of apprehension regarding privacy, data misuse, and the utilization of unproven treatments. Furthermore, individuals who did not complete the testing process had more difficulty making informed decisions due to increased uncertainty about their knowledge.
These findings will serve as a valuable guide in implementing focused interventions aimed at enhancing knowledge, trust, and decision-making certainty regarding genetic testing among patients with advanced PCa.
Ongoing studies will evaluate the effectiveness of interventions in improving the testing completion rate within a single institution.
Source: Purtell JP, Ralston A, Rose CM, et al. Race and decisional conflict about genetic testing in patients with advanced prostate cancer. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 2, 2024: abstract 5062.
Disparities have been extensively documented in prostate cancer screening uptake and shared decision-making conversations among racial and sexual minorities. Yet, the impact of racial/ethnic identity and sexual orientation on prostate-specific antigen (PSA) testing uptake remains uncertain.
This analysis used the 2018-2022 Behavioral Risk Factor Surveillance Survey data. Outcomes included survey responses to questions about engagement in shared decision-making and PSA testing uptake. In total, 88,365 heterosexual men and 2562 sexual minority men aged 55 to 69 years were included in this analysis.
The data were categorized by race/ethnicity, and survey-weighted logistic regression models were utilized to examine the relationship between sexual orientation and outcomes. Models were adjusted for age, marital status, level of education, household income, insurance coverage, having a regular healthcare provider, and geographical location.
In contrast to White heterosexual men, White sexual minority men demonstrated a greater tendency to discuss the disadvantages of PSA testing with their healthcare provider (odds ratio [OR], 1.407; P<.001) and to undergo PSA testing (OR, 1.320; P<.001).
Compared with Asian heterosexual men, Asian sexual minority men exhibited a greater tendency to engage in discussions regarding PSA testing (OR, 4.470; P<.05), discuss the benefits of PSA testing (OR, 4.596; P<.05), receive recommendations for PSA testing (OR, 4.836; P<.05), and undergo PSA testing (OR, 4.401; P<.001).
Black sexual minority men had a higher likelihood of undergoing screening due to a specific issue or reason other than routine screening (OR, 1.073; P<.05) in comparison to Black heterosexual men.
The likelihood of Hispanic sexual minority males undergoing screening as part of their routine checkup was notably higher (OR, 4.2; P<.001) when compared with Hispanic heterosexual males. No differences in sexual orientation were found in PSA screening or shared decision-making among American Indians or Native Alaskans.
Variations in the utilization of PSA testing and shared decision-making based on sexual orientation differ across racial and ethnic backgrounds. Additional research is necessary to examine the determinants influencing PSA testing uptake and shared decision-making among sexual minority men belonging to various racial and ethnic groups.
Biomarker testing is crucial in guiding treatment choices by pinpointing individuals who stand to gain from specific regimens, ultimately enhancing patient results. Nevertheless, the application of guideline-endorsed biomarker testing for advanced non-small cell lung cancer (NSCLC) patients varies.
This research delves into the frequency of biomarker testing among NSCLC patients through an in-depth, real-world data analysis.
The Amplity Insights™ database, which contains transcribed and de-identified records of physician-patient interactions from across the United States, underwent a search and analysis process using natural language processing.
This retrospective analysis focused on patients diagnosed with NSCLC between October 2003 and November 2023. The analysis involved summarizing and describing patient characteristics, biomarker testing, and treatment utilization.
This analysis included 61,018 patients diagnosed with NSCLC. The average age was 69.8 years, with a standard deviation of 10.5 years. Among them, 50.6% were female, and 87.9% identified as White. Additionally, 26.6% of the patients had early-stage disease (stage 0-II), and 73.4% had late-stage disease (stage III-IV). Among the entire cohort, evidence of biomarker testing was observed in 13.4% of all patients.
When considering different geographical regions in the United States, 13.3% of patients residing in the West, 11.9% in the Midwest, 16.9% in the Northeast, and 10.6% in the South were biomarker tested. Among patients with late-stage disease, 18.9% were biomarker tested, and the testing rates were higher when considering oncologist records only (24.5%).
Among the patients with a confirmed actionable mutation (6387 patients), 35.9% received a targeted therapy that was appropriately matched to their mutation. Of the patients with actionable mutations, 40.7% had epidermal growth factor mutations, 22.7% had anaplastic lymphoma kinase mutations, and 37.7% were programmed death-ligand 1-positive. Among these patients, 35.8%, 17.8%, and 40.2%, respectively, received the appropriate indicated treatment based on the results of the biomarker testing.
These results indicate that biomarker testing is potentially underutilized and that even when conducted, the appropriately targeted intervention may not be used, thus indicating that many patients are not deriving the full benefits of precision therapies.
Regional differences in biomarker testing rates were observed, indicating that other factors, such as social determinants, will likely influence patient access to biomarker testing. This underscores the importance of implementing further educational approaches to enhance precision oncology and improve patient outcomes.
Source: Videña V, Iwanyckyj D, Otalora F, Jardim M. Biomarker testing and targeted therapy use among patients with non-small cell lung cancer in the United States: an analysis using a physician notes real-world database. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 3, 2024: abstract 11175.
The demand for limited health resources and the significant financial burden associated with accessing healthcare necessitates a meticulous selection of treatments.
Treatment selection should be based on well-designed trials driven by societal needs and meaningful endpoints, financial and time toxicity, critical appraisal skills, the impact of including treatment options in universal health coverage and guidelines, and communication with patients about what they prioritize and available resources.
According to the World Bank and World Health Organization (WHO), 50% of the world lacks access to essential health services, and >100 million people are pushed into extreme poverty due to health expenses.
There is a huge discrepancy between health spending and cancer burden that translates into mortality due to limited access to health resources and poor quality of care. Additionally, there is an advanced stage of disease at diagnosis due to delays; there are few cancer services, there is high financial toxicity and out-of-pocket costs, limited access to essential anticancer drugs, palliative care, and pain services, and high volumes of cases per oncologists with >500 consults completed annually.
An extensive global study was conducted to understand oncologists’ views on what cancer treatments are essential and affordable. A secondary analysis of this study focusing on oncologists in India found that they selected all 20 treatments on the WHO Essential Medicines List, with 14 being conventional cytotoxic drugs.
Universal access to these treatments was found to be <50%. Additionally, 19% to 58% of oncologists reported risks of significant out-of-pocket expenditure for each treatment. And 58% to 67% of oncologists reported a risk of catastrophic expenditure for using rituximab and trastuzumab.
The overarching goal of Common Sense Oncology is to establish global equality in oncology. Every individual has the fundamental right to receive quality cancer care, and no patient should face barriers or financial hardships to access effective therapies.
The pricing of cancer treatments should be just and appropriate for the specific context in which they are employed. Prioritizing equitable access to high-quality care should be on par with promoting innovation and advancing novel treatments.
Source: Sengar M. Common Sense Oncology: why this matters for global health. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 3, 2024.
Messenger ribonucleic acid (mRNA)-4157 is an innovative approach to personalized neoantigen therapy. It utilizes mRNA to enhance the body’s natural immune response against tumor cells by targeting specific mutations unique to each patient.
Key findings from the phase 2 mRNA-4157-P201 (KEYNOTE-942) trial, with a median planned follow-up of 23 months, revealed that patients with completely resected high-risk stage IIIB–IV cutaneous melanoma who received a combination of mRNA-4157 and pembrolizumab experienced significantly prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) compared to those who received pembrolizumab alone.
The study design involved patients being allocated in a 2:1 ratio to receive mRNA-4157 (1 mg intramuscularly, maximum of 9 doses) in combination with pembrolizumab (200 mg intravenously, maximum of 18 cycles) or pembrolizumab alone. The primary endpoint of this study was the investigator’s assessment of RFS, and secondary endpoints included DMFS and safety. This planned analysis was conducted when the last randomly assigned patient had a follow-up of ≥2 years.
Additionally, translational subgroup analyses were performed, where human leukocyte antigens (HLA) genotypes were examined through exome sequencing of DNA obtained from peripheral blood mononuclear cells. Formal testing was not conducted for RFS and DMFS; the reported P-values are descriptive and nominal.
Following an additional year of observation (data cutoff, November 3, 2023; median [range], 34.9 [25.1–51.0] months) after the primary analysis, there were minimal new occurrences. The benefit of RFS in the combination treatment compared to pembrolizumab alone was sustained, showing a 49% risk reduction in recurrence and/or death (hazard ratio [HR], 95% confidence interval [CI], 0.510 [0.288–0.906]; 2-sided nominal P-value, 0.019).
The 2.5-year RFS rate for the combination treatment versus pembrolizumab alone was 74.8% versus 55.6%. Additionally, the combination treatment also demonstrated a clinically significant and lasting improvement in DMFS compared to pembrolizumab alone (HR [95% CI], 0.384 [0.172–0.858], 2-sided nominal P-value, 0.0154).
Overall survival (OS) favored the combination treatment over pembrolizumab alone, with a 2.5-year OS rate of 96.0% versus 90.2% (HR [95% CI], 0.425 [0.114–1.584]). The benefit of combination therapy compared to pembrolizumab alone in terms of RFS was consistent across various subgroups, including those with high tumor mutational burden (TMB), non-high TMB, programmed death-ligand 1 (PD-L1)-positive, PD-L1-negative, and circulating tumor DNA (ctDNA) negative.
However, the HR for the ctDNA-positive subgroup could not be estimated. No significant correlations were found between specific HLA alleles and RFS in either treatment arm. Interestingly, having maximal heterozygosity at HLA class I genotype loci (A, B, C) was associated with improved RFS compared to homozygosity for ≥1 locus in the pembrolizumab arm but not in the combination therapy arm.
The investigational mRNA-4157 was well tolerated, and the safety profile of combination therapy was consistent with previous findings, showing no increased risk of immune-related adverse events.
This analysis, which included a median follow-up of around ~3 years, revealed enduring and substantial long-term advantages in RFS and DMFS when using mRNA-4157 combined with pembrolizumab instead of pembrolizumab alone.
Furthermore, the combined treatment was indicated to potentially improve OS. Findings from HLA and translational subgroup assessments suggest that mRNA-4157 plus pembrolizumab might benefit a broader range of patients than pembrolizumab alone.
Source: Weber JS, Khattak MA, Carlino MS, et al. Individualized neoantigen therapy mRNA-4157 (V940) plus pembrolizumab in resected melanoma: 3-year update from the mRNA-4157-P201 (KEYNOTE-942) trial. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 3, 2024: abstract LBA9512.
MCLA-129 is a Biclonics-based product that can be categorized as a common light chain/bispecific antibody used to target EGFR and c-MET while enhancing antibody-dependent cellular cytotoxicity. This analysis outlines the current phase 1/2 clinical trial of MCLA-129 in individuals diagnosed with non-small cell lung cancer (NSCLC). This includes patients with MET exon 14 skipping (METex14) mutation (cohort A), EGFR exon 20 insertion (exon20ins)-mutated (cohort B), and sensitized EGFR-mutated disease (cohort C).
Patients were administered MCLA-129 intravenously (IV) biweekly, with doses ranging from 100 mg to 2000 mg, or weekly with doses of 1000 mg to 1500 mg, following a 28-day cycle in a dose-escalation study. This investigation also includes exploring the effects of doses at 1500 mg and 2000 mg IV biweekly in a dose-expansion phase.
The primary endpoint was to assess the treatment’s safety and tolerability. The objective response rate, as assessed by the investigator using RECIST (version 1.1) criteria, is reported for patients with NSCLC who were treated with doses of 1500 mg and 2000 mg IV biweekly in 3 separate cohorts.
As of January 29, 2024 260 patients with NSCLC, 2 with gastric cancer, and 1 with cholangiocarcinoma received MCLA-129 in China The most common treatment-emergent adverse events (TEAEs) included infusion-related reactions (71%), hypoalbuminemia (54%), decreased neutrophil count (46%), and a decreased white blood cell count (40%). The majority of TEAEs observed were grades 1-2. Grade ≥3 TEAEs and drug-related TEAEs were reported in 53% and 41% of patients, respectively.
In cohorts A, B, and C, the confirmed objective response rates (ORRs) were 43.4%, 28.6%, and 23.2%, respectively. Notably, patients in cohort A who received a prior MET tyrosine kinase inhibitor had an ORR of 38.2% with a disease control rate of 82.4%.
MCLA-129 demonstrated robust and durable antitumor activity in patients with NSCLC harboring METex14, EGFR exon20ins, and sensitized EGFR mutations, with a manageable safety profile. Enrollment in the dose-expansion study is currently ongoing.
Source: Wang J, Zhong J, Wu L, et al. Efficacy and safety of MCLA-129, an EGFR/c-MET bispecific antibody, in advanced non-small cell lung cancer (NSCLC). Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 3, 2024: abstract 8604.
Clinical trials serve as the foundation for innovative treatments; however, they may not accurately reflect the experiences of marginalized populations, specifically those with low incomes.
This study examines the influence of social vulnerability on clinical trial participation rates and delves into the relationship between race and social vulnerability in patients affected by the most common causes of cancer-related mortality.
The Vizient Clinical Database was utilized to gather information on outpatients diagnosed with lung, breast, prostate, colorectal, or pancreatic cancer between 2022 and 2023. This comprehensive database includes data from 98% of academic medical centers and more than 110 cancer hospitals.
The study focused on Medicaid insurance and social vulnerability, which were measured using the Vizient Vulnerability Index (VVI). The VVI is a unique tool that assesses social determinants of health at the census tract level.
The primary outcome of interest was patients’ participation in a clinical trial. A multivariable analysis was conducted to evaluate the relationship between social vulnerability quartiles and clinical trial participation. Additionally, interaction tests were performed to examine the impact of race and VVI on the outcomes.
A total of 2,660,566 patients were identified, 1.5% enrolling in a clinical trial. The distribution among different types included breast cancer, 28.6%; prostate cancer, 26.3%; lung cancer, 22.8%; colorectal cancer, 12.8%; and pancreatic cancer, 9.5%.
Characteristics of trial participants included being young, White, privately insured, having metastatic disease, and residing in less vulnerable census tracts. Additionally, 22.6% of participants lived in highly vulnerable neighborhoods, with significant differences observed among racial groups compared with nonparticipants. Living in a more vulnerable census tract was found to be linked to a lower likelihood of participating in clinical trials (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.81-0.91; P=.0442).
Similarly, individuals with Medicaid insurance, as opposed to private insurance, also had decreased odds of enrollment in clinical trials (OR, 0.76; 95% CI, 0.73-0.80; P<.0001). The highest quartiles of social vulnerability in terms of education, neighborhood resources, and transportation were associated with reduced enrollment rates.
Notably, high social vulnerability had an impact on decreasing enrollment for Black patients (OR, 0.80; 95% CI, 0.68-0.88; P<.0001) and White patients (OR, 0.88; 95% CI, 0.89-0.96; P=.0028); however, high social vulnerability decreased the odds of clinical trial enrollment for Black patients more than White patients and the interaction between race and social vulnerability was statistically significant (P=.0054).
Overall, the level of social vulnerability in a neighborhood hinders clinical trial enrollment, particularly among Black participants. Initiatives aimed at addressing social determinants of health might lead to a more diverse racial composition in clinical trials.
Source: Perati SR, Mohayya SM, Shippey E, et al. Social vulnerability and clinical trial enrollment: the next frontier of health equity. 2024 ASCO Annual Meeting. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 4, 2024: abstract 1508.
Recent research indicates that patients with tumor mutational burden (TMB)-high tumors may experience positive clinical outcomes when treated with atezolizumab, a programmed death-ligand 1 (PD-L1) inhibitor. Nevertheless, previous studies have employed varying TMB cutoffs.
This study presents the effectiveness and safety profile of atezolizumab in adult and pediatric patients with TMB-high advanced/metastatic solid tumors from cohort D of the TAPISTRY trial (NCT04589845), utilizing 2 distinct TMB cutoffs: ≥16 mutations (mut)/Mb and ≥13 mut/Mb.
TAPISTRY is a phase 2 clinical trial conducted globally. It has an open-label design and multiple cohorts, and it aims to evaluate the effectiveness and safety of multiple treatments in patients with advanced or metastatic solid tumors who have undergone prior treatment.
Patients in cohort D presented with advanced unresectable or metastatic solid tumors, were treatment-naïve to PD-L1 inhibitors, and had a TMB-high status (≥13 mut/Mb). Atezolizumab was administered every 21 days at a dose of 1200 mg for patients aged ≥18 years and at a dose of 15 mg/kg (up to 1200 mg) for patients aged <18 years.
Tumor responses were evaluated according to RECIST (version 1.1) criteria. The primary endpoint of the study was the objective response rate (ORR) determined by an independent review committee (IRC) in patients with TMB of ≥16 mut/Mb. Secondary endpoints included ORR by IRC in patients with TMB of ≥13 mut/Mb, duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety assessments.
The study included 150 patients with a TMB of ≥13 mut/Mb. The safety-evaluable group, consisting of 148 patients, had a median age of 63 years, 56.1% were male, and 24.3% had undergone ≥2 prior lines of therapy.
The efficacy-evaluable group included 129 patients with a TMB of ≥13 mut/Mb or higher (with 111 patients having a TMB of ≥16 mut/Mb); the most prevalent tumor types were colorectal (31.0% with 40 patients), breast, and gastroesophageal cancer (9% with 11 patients, each). The ORR, as assessed by the IRC, was similar between patients with a TMB of ≥16 mut/Mb (22.5%) and those with a TMB ≥13 mut/Mb (20.2%).
Various tumor types exhibited responses. Median DoR was not reached for either TMB of ≥16 mut/Mb or TMB of ≥13 mut/Mb. The median PFS was 2.8 months (95% confidence interval [CI], 1.7-5.4) for patients with TMB of ≥16 mut/Mb and 2.7 months (95% CI, 1.5-4.2) for patients with TMB of ≥13 mut/Mb and.
The median OS was 15.0 months (95% CI, 9.1-21.5) for patients with TMB of ≥16 mut/Mb and 16.1 months (95% CI, 9.1-21.4) for patients with TMB of ≥13 mut/Mb. Regarding the existence of adverse events, fatigue (22.3%) and anemia (19.6%) were prevalent. The safety profile of atezolizumab remained in line with its established characteristics.
Atezolizumab demonstrated proficient tolerability, resulting in anti-tumor effects in patients with TMB-high solid tumors. Positive responses were observed in different types of tumors and patients who responded to treatment responded for a prolonged time.
Source: Dziadziuszko R, Barlesi F, Kim JE, et al. Atezolizumab in patients (pts) with tumor mutational burden (TMB)–high tumors from the TAPISTRY trial. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 4, 2024: abstract LBA2509.
Disparities in the treatment and outcomes of Black patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC) have been documented. There is a lack of data regarding the racial equity of targeted treatment utilization for patients with ER-positive and HER2-negative mBC.
This study analyzed variances in circulating tumor DNA (ctDNA) genomic alterations between Black and White patients with ER-positive, HER2-negative mBC.
In this retrospective cohort study, 1327 patients with mBC underwent ctDNA testing using the Guardant360 assay at Washington University, Massachusetts General Hospital, and Northwestern University. The patients were stratified based on progesterone receptor (PR) status into ER-positive/PR-positive/HER2-negative and ER-positive/PR-negative/HER2-negative subgroups. Overall, 708 (89%) White patients and 87 (11%) Black patients with an ER-positive/HER2-negative subtype were evaluated in this study.
Patients were assessed based on their self-reported race and their utilization of ptdIns-3-kinase subunit alpha (PIK3CA), cyclin-dependent kinase (CDK)4/6, and mammalian target of rapamycin (mTOR) inhibitors by participating in clinical trials or following FDA approval. A multivariate logistic analysis was carried out to identify genomic and prognostic variations across different racial groups, with overall survival (OS) calculated from the time of ctDNA testing.
Black patients with PIK3CA single nucleotide variants were significantly less likely to receive targeted therapy than White patients (5.9% vs 28.8% of patients; P=.045), and there was no difference in the detection frequency of PIK3CA mutations between Black (36%) and White (34%) patients. There was no difference in the use of CDK4/6 or mTOR inhibitors. None of the Black patients with PIK3CA mutations were enrolled in clinical trials, compared with 11.5% of White patients.
The likelihood of CCND1 copy number variation was higher in Black patients with ER-positive/PR-positive/HER2-negative tumors than in White patients.
Black patients with PR-negative tumors were more likely to have GATA3 SNV relative to White patients whereas White PR-negative patients were more likely to harbor a higher KRAS copy number variation prevalence than Black patients.
Among patients with ER-positive/PR-negative/HER2-negative mBC, Black patients had a median OS of 9.1 months, whereas White patients had a median OS of 21 months (P=.00093).
This may be the largest clinic-genomic dataset to date, enabling the comparison of genomic alterations and targeted treatment utilization among different races in mBC.
This analysis revealed notable discrepancies in the use of select inhibitors in Black patients with mBC. The observed differences in OS and participation in clinical trials align with previous studies. Further research is necessary to better understand the drivers of these disparities and ensure all patients have access to treatments.
Source: Podany EL, Foffano L, Gerratana L, et al. Racial differences in genomic profiles and targeted treatment use in ER+ HER2- metastatic breast cancer. Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 4, 2024: abstract 1017.
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