The performance status gap in immunotherapy for frail patients with advanced non-small cell lung cancer.

PURPOSE: In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown. METHODS: Patients in the veterans affairs national precision oncology program from 1/2019-12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy. RESULTS: Of 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 - 0.88; Poor PS: OR 0.69, 95% CI 0.44 - 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 - 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 - 1.58). CONCLUSION: Frail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.

The Landscape of Care for Women Veterans with Cancer: An Evidence Map.

BACKGROUND: Women are the fastest growing veteran group in the US and the number of women veterans (WVs) with cancer is rising; however, little is known about this population. Cancer care for WVs is complex and it is essential to understand their unique needs and care coordination challenges to provide evidence-based care. The purpose of this review is to map the quantity, distribution, and characteristics of literature describing cancer and its treatment among WVs. METHODS: We searched MEDLINE (via PubMed), Embase (Elsevier), and Web of Science Core Collection (Clarivate) from inception through January, 2024. Publications were eligible that reported gender-specific data on any aspect of cancer care among WVs. Data was abstracted by a single investigator with over-reading. RESULTS: Forty-six reports were included; 44 were observational and 19 had a women-only sample. There were no interventional reports and no qualitative reports had a patient sample. Breast cancer was the most commonly addressed (n = 19). There were six additional reports on sex-specific cancers. Many reports used large VA databases or previous trial data, creating the potential for patient overlap between reports. Among VA-specific areas of interest, only three reports evaluated the potential implications of racial differences and only two included a transgender population. No reports examined the effects of toxic exposures on cancer. Within the NCI Cancer Control Continuum, crosscutting areas were more commonly represented; over half (25) of the reports addressed epidemiology. There were few reports on focus areas and little overlap between focus and crosscutting areas. DISCUSSION: Existing literature provides an inadequate understanding of the population of WVs with cancer. There is scant information regarding the population of WVs with cancer, their care preferences or experiences, or how to best identify and address unmet healthcare needs. It is imperative to expand research to provide evidence-based care for this population.

Teleoncology in the Veterans Health Administration: Models of Care and the Veteran Experience.

The Veterans Health Administration (VHA) has pioneered teleoncology to address access challenges faced by Veterans requiring cancer care. This ASCO Educational Book highlights the development of teleoncology programs within the VHA: the local VA Pittsburgh Healthcare System (VAPHS) Virtual Cancer Care Center, the National TeleOncology Program (NTO), and the regional Clinical Resource Hub (CRH) Oncology Program. These initiatives provide oncology care using a hub-and-spoke model, which centralizes expertise at hub sites and reaches Veterans at distant spoke sites through synchronous and asynchronous care. The deployment of these teleoncology programs has resulted in significant benefits, such as decreased travel for Veterans, high levels of patient satisfaction, and improved access to specialized treatments. Despite these advancements, disparities in teleoncology utilization and access to clinical trials persist. This educational manuscript highlights the successes and challenges of tele-oncology within the VHA, underscoring the critical role of telehealth in overcoming access barriers.

Summary of Veterans Health Administration Cancer Data Sources.

Objectives: The Veterans Health Administration (VHA) is a leader in generating transformational research across the cancer care continuum. Given the extensive body of cancer-related literature utilizing VHA data, our objectives are to: (1) describe the VHA data sources available for conducting cancer-related research, and (2) discuss examples of published cancer research using each data source. Methods: We identified commonly used data sources within the VHA and reviewed previously published cancer-related research that utilized these data sources. In addition, we reviewed VHA clinical and health services research web pages and consulted with a multidisciplinary group of cancer researchers that included hematologist/oncologists, health services researchers, and epidemiologists. Results: Commonly used VHA cancer data sources include the Veterans Affairs (VA) Cancer Registry System, the VA Central Cancer Registry (VACCR), the Corporate Data Warehouse (CDW)-Oncology Raw Domain (subset of data within the CDW), and the VA Cancer Care Cube (Cube). While no reference standard exists for cancer case ascertainment, the VACCR provides a systematic approach to ensure the complete capture of clinical history, cancer diagnosis, and treatment. Like many population-based cancer registries, a significant time lag exists due to constrained resources, which may make it best suited for historical epidemiologic studies. The CDW-Oncology Raw Domain and the Cube contain national information on incident cancers which may be useful for case ascertainment and prospective recruitment; however, additional resources may be needed for data cleaning. Conclusions: The VHA has a wealth of data sources available for cancer-related research. It is imperative that researchers recognize the advantages and disadvantages of each data source to ensure their research questions are addressed appropriately.

Telehealth Research and Innovation for Veterans with Cancer: the THRIVE Center.

BACKGROUND: In recent years the US health-care system has witnessed a substantial increase in telehealth use. Telehealth enhances health-care access and quality and may reduce costs. However, there is a concern that the shift from in-person to telehealth care delivery may differentially improve cancer care access and quality in certain clinical settings and for specific patient populations while potentially exacerbating disparities in care for others. Our National Cancer Institute-funded center, called Telehealth Research and Innovation for Veterans with Cancer (THRIVE), is focused on health equity for telehealth-delivered cancer care. We seek to understand how social determinants of telehealth-particularly race and ethnicity, poverty, and rurality-affect the use of telehealth. METHODS: THRIVE draws from the Health Disparities Research Framework and the Consolidated Framework for Implementation Research. THRIVE consists of multiple cores that work synergistically to assess and understand health equity for telehealth-delivered cancer care. These include the Administrative Core, Research and Methods Core, Clinical Practice Network, and Pragmatic Trial. RESULTS: As of October 2023, we identified and trained 5 THRIVE scholars, who are junior faculty beginning a research career. We have reviewed 20 potential pilot studies, funding 6. Additionally, in communication with our funders and advisory boards, we have adjusted our study design and analytic approach, ensuring feasibility while addressing our operational partners' needs. CONCLUSIONS: THRIVE has several key strengths. First, the Veterans Health Administration's health-care system is large and diverse regarding health-care setting type and patient population. Second, we have access to longitudinal data, predating the COVID-19 pandemic, about telehealth use. Finally, equitable access to high-quality care for all veterans is a major tenet of the Veterans Health Administration health-care mission. As a result of these advantages, THRIVE can focus on isolating and evaluating the impact of social determinants of telehealth on equity in cancer care.

Brief Report: Real-World Efficacy and Safety of Sotorasib in U.S. Veterans with KRAS G12C-Mutated NSCLC.

Introduction: The KRAS G12C inhibitor sotorasib was approved for treating advanced NSCLC in the second line or later on the basis of the CodeBreaK100 trial. Nevertheless, data on the real-world efficacy and safety of sotorasib, and to its optimal dose, remain limited. Methods: Patients treated with sotorasib for NSCLC through the Veterans Health Administration were retrospectively identified from the Corporate Data Warehouse. Survival, response, and toxicity data were obtained from chart review. Results: Among the 128 patients treated with sotorasib through the Veterans Health Administration, objective response rate was 34%, progression-free survival (PFS) six months, and overall survival 12 months. Similar PFS was observed among the 16 patients who received frontline sotorasib without any prior systemic therapy for NSCLC. Toxicity leading to sotorasib interruption or dose reduction occurred in 37% of patients, whereas sotorasib discontinuation for toxicity occurred in 25%. Notably, sotorasib dose reduction was associated with substantially improved PFS and OS. Conclusions: In this real-world study, the observed efficacy of sotorasib was similar to the results of CodeBreaK100. Patients who received frontline sotorasib had similar PFS to our overall cohort, suggesting that first-line sotorasib monotherapy may benefit patients who are not eligible for chemotherapy. Toxicities leading to sotorasib interruption, dose reduction, or discontinuation were common. Sotorasib dose reduction was associated with improved survival, suggesting that sotorasib dose reduction may not compromise efficacy.

Pharmacogenetic and clinical risk factors for bevacizumab-related gastrointestinal hemorrhage in prostate cancer patients treated on CALGB 90401 (Alliance).

The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone ± bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n = 503) and placebo (n = 505) treated patients, respectively. Bevacizumab (P < 0.001) and age (P = 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n = 314 bevacizumab and n = 302 placebo treated patients), grade 2 or higher gastrointestinal hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19-12.28; P = 9.40 × 10-8) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage.

Adaption and National Validation of a Tool for Predicting Mortality from Other Causes Among Men with Nonmetastatic Prostate Cancer.

BACKGROUND: An electronic health record-based tool could improve accuracy and eliminate bias in provider estimation of the risk of death from other causes among men with nonmetastatic cancer. OBJECTIVE: To recalibrate and validate the Veterans Aging Cohort Study Charlson Comorbidity Index (VACS-CCI) to predict non-prostate cancer mortality (non-PCM) and to compare it with a tool predicting prostate cancer mortality (PCM). DESIGN, SETTING, AND PARTICIPANTS: An observational cohort of men with biopsy-confirmed nonmetastatic prostate cancer, enrolled from 2001 to 2018 in the national US Veterans Health Administration (VA), was divided by the year of diagnosis into the development (2001-2006 and 2008-2018) and validation (2007) sets. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Mortality (all cause, non-PCM, and PCM) was evaluated. Accuracy was assessed using calibration curves and C statistic in the development, validation, and combined sets; overall; and by age (<65 and 65+ yr), race (White and Black), Hispanic ethnicity, and treatment groups. RESULTS AND LIMITATIONS: Among 107 370 individuals, we observed 24 977 deaths (86% non-PCM). The median age was 65 yr, 4947 were Black, and 5010 were Hispanic. Compared with CCI and age alone (C statistic 0.67, 95% confidence interval [CI] 0.67-0.68), VACS-CCI demonstrated improved validated discrimination (C statistic 0.75, 95% CI 0.74-0.75 for non-PCM). The prostate cancer mortality tool also discriminated well in validation (C statistic 0.81, 95% CI 0.78-0.83). Both were well calibrated overall and within subgroups. Owing to missing data, 18 009/125 379 (14%) were excluded, and VACS-CCI should be validated outside the VA prior to outside application. CONCLUSIONS: VACS-CCI is ready for implementation within the VA. Electronic health record-assisted calculation is feasible, improves accuracy over age and CCI alone, and could mitigate inaccuracy and bias in provider estimation. PATIENT SUMMARY: Veterans Aging Cohort Study Charlson Comorbidity Index is ready for application within the Veterans Health Administration. Electronic health record-assisted calculation is feasible, improves accuracy over age and Charlson Comorbidity Index alone, and might help mitigate inaccuracy and bias in provider estimation of the risk of non-prostate cancer mortality.

Researcher Experience and Comfort With Telemedicine and Remote Patient Monitoring in Cancer Treatment Trials.

BACKGROUND: Since the onset of COVID-19, oncology practices across the US have integrated telemedicine (TM) and remote patient monitoring (RPM) into routine care and clinical trials. The extent of provider experience and comfort with TM/RPM in treatment trials, however, is unknown. We surveyed oncology researchers to assess experience and comfort with TM/RPM. METHODS: Between April 10 and June 1, 2022, we distributed email surveys to US-based members of the American Society of Clinical Oncology (ASCO) whose member records indicated interest or specialization in clinical research. We collected respondent demographic data, clinical trial experience, workplace characteristics, and comfort and experience with TM/RPM use across trial components in phase I and phase II/III trials. TM/RPM was defined as clinical trial-related healthcare and monitoring for patients geographically separated from trial site. RESULTS: There were 141 surveys analyzed (5.1% response rate). Ninety percent of respondents had been Principal Investigators, 98% practiced in a norural site. Most respondents had enrolled patients in phase I (82%) and phase II/III trials (99%). Across all phases and trial components, there was a higher frequency of researcher comfort compared to experience. Regarding remote care in treatment trials, 75% reported using TM, RPM, or both. Among these individuals, 62% had never provided remote care to trial patients before the pandemic. CONCLUSION: COVID-19 spurred the rise of TM/RPM in cancer treatment trials, and some TM/RPM use continues in this context. Among oncology researchers, higher levels of comfort compared with real-world experience with TM/RPM reveal opportunities for expanding TM/RPM policies and guidelines in oncology research.

Utility of Tumor Mutational Burden as a Biomarker for Response to Immune Checkpoint Inhibition in the VA Population.

PURPOSE: Immune checkpoint inhibitors (ICIs) are used for an increasing number of indications across various tumor types, as well as several tumor-agnostic indications in patients with advanced cancer. Although many patients benefit from ICI therapy, others do not, highlighting a need for better predictive biomarkers. Tumor mutational burden (TMB) reflects the global number of mutations within a tumor and has been widely explored as a predictive biomarker of ICI response. The current tumor type-agnostic US Food and Drug Administration approval of pembrolizumab for metastatic solid tumors defines high TMB (TMB-H) as ≥10 mut/Mb as measured by FoundationOne CDx. This fixed cutoff may not be the ideal value across all solid tumors. METHODS: We performed a retrospective analysis of the association of survival outcomes with TMB in patients treated with ICI for five major cancer types, using real-world data from the VA. Survival was measured from initiation of ICI, and Kaplan-Meier survival curves were compared by log-rank test. RESULTS: Overall survival (OS) was significantly longer for patients with TMB-H versus TMB low tumors in non-small-cell lung cancer (NSCLC; n = 1,593), head and neck (H&N) cancer (n = 222), and urothelial cancer (n = 332). OS was not significantly different based on TMB status in melanoma (n = 207) or esophageal/gastric cancer (n = 248). CONCLUSION: Consistent with previous studies, a predictive value of TMB ≥10 mut/Mb for ICI response was found in NSCLC and H&N, but not in esophageal/gastric cancer. Although inconclusive in the literature, significant association was found in urothelial cancer. The predictive value of TMB in melanoma was inconclusive. Our analysis does not support the use of a fixed threshold for TMB as a standalone predictive biomarker for ICI across all solid tumors.

Adopting Weight-Based Dosing With Pharmacy-Level Stewardship Strategies Could Reduce Cancer Drug Spending By Millions.

Immune checkpoint inhibitors, a class of drugs used in approximately forty unique cancer indications, are a sizable component of the economic burden of cancer care in the US. Instead of personalized weight-based dosing, immune checkpoint inhibitors are most commonly administered at "one-size-fits-all" flat doses that are higher than necessary for the vast majority of patients. We hypothesized that personalized weight-based dosing along with common stewardship efforts at the pharmacy level, such as dose rounding and vial sharing, would lead to reductions in immune checkpoint inhibitor use and lower spending. Using data from the Veterans Health Administration (VHA) and Medicare drug prices, we estimated reductions in immune checkpoint inhibitor use and spending that would be associated with pharmacy-level stewardship strategies, in a case-control simulation study of individual patient-level immune checkpoint inhibitor administration events. We identified baseline annual VHA spending for these drugs of approximately $537 million. Combining weight-based dosing, dose rounding, and pharmacy-level vial sharing would generate expected annual VHA health system savings of $74 million (13.7 percent). We conclude that adoption of pharmacologically justified immune checkpoint inhibitor stewardship measures would generate sizable reductions in spending for these drugs. Combining these operational innovations with value-based drug price negotiation enabled by recent policy changes may improve the long-term financial viability of cancer care in the US.

On-Site Nurse-Led Cancer Genetics Program Increases Cancer Genetic Testing Completion in Black Veterans.

PURPOSE: Telegenetics services can expand access to guideline-recommended cancer genetic testing. However, access is often not distributed equitably to all races and ethnicities. We evaluated the impact of an on-site nurse-led cancer genetics service in a diverse Veterans Affairs Medical Center (VAMC) oncology clinic on likelihood of germline testing (GT) completion. METHODS: We conducted an observational retrospective cohort study of patients who were referred for cancer genetics services at the Philadelphia VAMC between October 1, 2020, and February 28, 2022. We evaluated the association between genetics service (on-site v telegenetics) and likelihood of GT completion in a subcohort of new consults, excluding patients with prior consults and those referred for known history of germline mutations. RESULTS: A total of 238 Veterans, including 108 (45%) seen on site, were identified for cancer genetics services during the study period, with the majority referred for a personal (65%) or family (26%) history of cancer. In the subcohort of new consults, 121 Veterans (54% self-identified race/ethnicity [SIRE]-Black), including 60 (50%) seen on site, were included in the analysis of germline genetic testing completion. In a univariate analysis, patients who were seen by the on-site genetics service had 3.2-fold higher likelihood of completing GT (relative risk, 3.22; 95% CI, 1.89 to 5.48) compared with the telegenetics service. In multivariable regression analysis, the on-site genetics service was associated with higher likelihood of GT completion, but this association was only statistically significant in SIRE-Black compared with SIRE-White Veterans (adjusted RR, 4.78; 95% CI, 1.53 to 14.96; P < .001; P-interaction of race × genetics service = .016). CONCLUSION: An on-site nurse-led cancer genetics service embedded in a VAMC Oncology practice was associated with higher likelihood of germline genetic testing completion than a telegenetics service among self-identified Black Veterans.

Spectroscopic identification of water emission from a main-belt comet.

Main-belt comets are small Solar System bodies located in the asteroid belt that repeatedly exhibit comet-like activity (that is, dust comae or tails) during their perihelion passages, strongly indicating ice sublimation1,2. Although the existence of main-belt comets implies the presence of extant water ice in the asteroid belt, no gas has been detected around these objects despite intense scrutiny with the world's largest telescopes3. Here we present James Webb Space Telescope observations that clearly show that main-belt comet 238P/Read has a coma of water vapour, but lacks a significant CO2 gas coma. Our findings demonstrate that the activity of comet Read is driven by water-ice sublimation, and implies that main-belt comets are fundamentally different from the general cometary population. Whether or not comet Read experienced different formation circumstances or evolutionary history, it is unlikely to be a recent asteroid belt interloper from the outer Solar System. On the basis of these results, main-belt comets appear to represent a sample of volatile material that is currently unrepresented in observations of classical comets and the meteoritic record, making them important for understanding the early Solar System's volatile inventory and its subsequent evolution.

Multiple Schedules Facilitate Rapid Noncontingent Reinforcement Schedule Thinning.

We evaluated a noncontingent reinforcement treatment that included initial brief exposures to signaled alternation of availability and nonavailability of reinforcement, followed by rapid schedule thinning. Results confirmed findings from previous research (typically with differential reinforcement schedules) that establishing stimulus control across multiple treatment components facilitated schedule thinning. We discuss both the clinical utility of this procedure and the utility of stimulus control for making interventions more practical for clinicians.

Actionable Genomic Alterations in Prostate Cancer Among Black and White United States Veterans.

Black Veterans have higher a incidence of localized and metastatic prostate cancer compared to White Veterans yet are underrepresented in reports of frequencies of somatic and germline alterations. This retrospective analysis of somatic and putative germline alterations was conducted in a large cohort of Veterans with prostate cancer (N = 835 Black, 1613 White) who underwent next generation sequencing through the VA Precision Oncology Program, which facilitates molecular testing for Veterans with metastatic cancer. No differences were observed in gene alterations for FDA approved targetable therapies (13.5% in Black Veterans vs. 15.5% in White Veterans, P = .21), nor in any potentially actionable alterations (25.5% vs. 28.7%, P =.1). Black Veterans had higher rates of BRAF (5.5% vs. 2.6%, P < .001) alterations, White Veterans TMPRSS2 fusions (27.2% vs. 11.7%, P < .0001). Putative germline alteration rates were higher in White Veterans (12.0% vs. 6.1%, P < .0001). Racial disparities in outcome are unlikely attributable to acquired somatic alterations in actionable pathways.

Risk factors of SARS-CoV-2 infection and complications from COVID-19 in lung cancer patients.

BACKGROUND: Identifying lung cancer patients at an increased risk of getting SARS-CoV-2-related complications will facilitate tailored therapy to maximize the benefit of anti-cancer therapy, while decreasing the likelihood of COVID-19 complications. This analysis aimed to identify the characteristics of lung cancer patients that predict for increased risk of death or serious SARS-CoV-2 infection. PATIENTS AND METHODS: This was a retrospective cohort study of patients with lung cancer diagnosed October 1, 2015, and December 1, 2020, and a diagnosis of COVID-19 between February 2, 2020, and December 1, 2020, within the Veterans Health Administration. Serious SARS-CoV-2 infection was defined as hospitalization, ICU admission, or mechanical ventilation or intubation within 2 weeks of COVID-19 diagnosis. For categorical variables, differences were assessed using Χ2 tests, while Kruskal-Wallis rank-sum test was used for continuous variables. Multivariable logistic regression models were fit relative to onset of serious SARS-CoV-2 infection and death from SARS-CoV-2 infection. RESULTS: COVID-19 infection was diagnosed in 352 lung cancer patients. Of these, 61 patients (17.3%) died within four weeks of diagnosis with COVID-19, and 42 others (11.9%) experienced a severe infection. Patients who had fatal or severe infection were older and had lower hemoglobin levels than those with mild or moderate infection. Factors associated with death from SARS-CoV-2 infection included increasing age, immune checkpoint inhibitor therapy and low hemoglobin level. CONCLUSIONS:  The mortality of lung cancer patients from COVID-19 disease in the present cohort was less than previously reported in the literature. The identification of risk factors associated with severe or fatal outcomes informs management of patients with lung cancer who develop COVID-19 disease.

Real-world Experience With Neurotrophic Tyrosine Receptor Kinase Fusion-positive Tumors and Tropomyosin Receptor Kinase Inhibitors in Veterans.

PURPOSE: Neurotrophic tyrosine receptor kinase 1-3 (NTRK1-3) gene fusions are found in a broad range of tumor types. Clinical trials demonstrated high response rates to tropomyosin receptor kinase (TRK) inhibitors in NTRK fusion-positive cancers, but few reports have described real-world experience with these targeted agents. We evaluated the prevalence of NTRK fusions and the outcomes with TRK inhibitor therapy in a real-world population of patients in the Veterans Health Administration. METHODS: Patients with NTRK fusions or rearrangements were identified from the Veterans Affairs (VA) National Precision Oncology Program (NPOP), and patients who were prescribed TRK inhibitors were identified from the Corporate Data Warehouse. Baseline data and clinical outcomes were obtained by retrospective review of medical records. RESULTS: A total of 33 patients with NTRK fusions or rearrangements were identified, including 25 patients comprising 0.12% of all patients with solid tumors sequenced through VA NPOP. Twelve patients with NTRK fusions or rearrangements were treated with TRK inhibitors, none of whom had objective responses. Eight patients experienced toxicities leading to drug interruption, dose reduction, or discontinuation. CONCLUSION: In this retrospective study of VA patients, NTRK fusions and rearrangements were less common than in previous studies, and objective responses to TRK inhibitors were not observed. Real-world experience with TRK inhibitors differs markedly from clinical trial findings, possibly due to differences in patient demographics, tumor types, and sequencing methods. Our findings highlight the need to study TRK inhibitors in the real-world setting and in populations underrepresented in clinical trials.

Health outcomes and healthcare resource utilization among Veterans with stage IV non-small cell lung cancer treated with second-line chemotherapy versus immunotherapy.

BACKGROUND: Until recently, multi-agent chemotherapy (CT) was the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Clinical trials have confirmed benefits in overall survival (OS) and progression-free survival with immunotherapy (IO) compared to CT. This study compares real-world treatment patterns and outcomes between CT and IO administrations in second-line (2L) settings for patients with stage IV NSCLC. MATERIALS AND METHODS: This retrospective study included patients in the United States Department of Veterans Affairs healthcare system diagnosed with stage IV NSCLC during 2012-2017 and receiving IO or CT in the 2L. Patient demographics and clinical characteristics, healthcare resource utilization (HCRU), and adverse events (AEs) were compared between treatment groups. Logistic regression was used to examine differences in baseline characteristics between groups, and inverse probability weighting multivariable Cox proportional hazard regression was used to analyze OS. RESULTS: Among 4,609 Veterans who received first-line (1L) therapy for stage IV NSCLC, 96% received 1L CT alone. A total of 1,630 (35%) were administered 2L systemic therapy, with 695 (43%) receiving IO and 935 (57%) receiving CT. Median age was 67 years (IO group) and 65 years (CT group); most patients were male (97%) and white (76-77%). Patients administered 2L IO had a higher Charlson Comorbidity Index than those administered CT (p = 0.0002). 2L IO was associated with significantly longer OS compared with CT (hazard ratio 0.84, 95% CI 0.75-0.94). IO was more frequently prescribed during the study period (p < 0.0001). No difference in rate of hospitalizations was observed between the two groups. CONCLUSIONS: Overall, the proportion of advanced NSCLC patients receiving 2L systemic therapy is low. Among patients treated with 1L CT and without IO contraindications, 2L IO should be considered, as this supports potential benefit of IO for advanced NSCLC. The increasing availability and indications for IO will likely increase the administration of 2L therapy to NSCLC patients.