Targeted Therapy Use Research Articles

Improvements in Clinical Cancer Care Associated with Integration of Personalized Medicine.

While adoption of personalized medicine (PM) continues to increase in clinical oncology, there is limited data connecting the level of PM adoption at a given institution to improved clinical outcomes for patients. The purpose of this study was to analyze the correlation between health care providers' scores on a previously described PM integration framework and two outcome measures: the use of targeted therapy and clinical trial enrollment. This study was conducted using real-world data (RWD) from the Syapse® Learning Health Network (LHN). The PM integration score for six community hospital systems in the LHN was calculated and subsequently correlated with the two outcome measures. Across six institutions, a strong correlation between PM integration score and targeted therapy use was observed in metastatic non-small cell lung cancer (mNSCLC) (R2 = 0.81), an indication with a significant number of approved targeted agents. Conversely, a strong correlation between PM integration score and clinical trial enrollment was observed in metastatic triple-negative breast cancer (TNBC) (R2 = 0.63), an indication with fewer marketed targeted therapies but an active targeted therapy pipeline. The results in these cases suggest that PM integration is a strong indicator of high-quality care practices for both utilization of targeted therapy in more mature PM indications (e.g., mNSCLC) and clinical trial enrollment in more emerging PM indications (e.g., TNBC).

The 340B Program and High-Risk Prescribing of Oral Targeted Therapies for Advanced Prostate Cancer.

The use of expensive oral targeted agents for advanced prostate cancer can be influenced by those who stand to gain from their use. The 340B drug pricing program allows eligible hospitals to purchase medications at steep discounts, generating millions of dollars in savings. The extent to which hospitals engage in higher-risk prescribing due to program incentives is unclear. Medicare claims were used to perform a retrospective study of men with advanced prostate cancer. The primary outcome was targeted therapy use in men with high noncancer mortality risk. Secondary outcomes included androgen biosynthesis inhibitor use in men with cardiovascular history, androgen receptor inhibitor use in men with neurocognitive history, and therapy within 14 days of death. Proportional hazards models were used to assess time-to-event outcomes, while logistic regression was used for binary outcomes. In men with high noncancer mortality risk, targeted therapy use did not differ at 340B participating compared to nonparticipating hospitals (hazard ratio [HR] 1.1, 95% CI 0.67-1.5). There was no difference in androgen biosynthesis inhibitor use in men with a prior cardiac event (HR 0.96, 95% CI 0.70-1.3) or androgen receptor inhibitor use in men with a prior neurocognitive event (HR 1.5, 95% CI 0.65-3.4) in those treated at 340B participating compared to nonparticipating hospitals. Therapy use in the last 14 days of life did not vary by 340B participation (odds ratio 1.3, 95% CI 0.86-1.9). In men with advanced prostate cancer, high-risk prescribing and futility measures did not vary by participation in the 340B drug pricing program.

Differences in baseline characteristics and healthcare costs among insured patients with advanced cancer with vs without clinical trial participation.

11154 Background: Despite concerted efforts to improve clinical trial participation (CTP), enrollment remains low. Perceived additional costs to the patient or health plan may be barriers to CTP; low biomarker testing rates may be another. This study assessed differences in characteristics of patients with CTP versus patients without CTP in an insured population with advanced cancer. Methods: A retrospective analysis was conducted using de-identified administrative claims data from commercially insured and Medicare Advantage (MA) enrollees in the Optum Labs Data Warehouse. Patients ≥18y with claims evidence of advanced cancer and systemic therapy between 01/01/2018 and 02/28/2022 were stratified into 2 groups: 1) with CTP: ≥1 claim with a CTP diagnosis (ICD10 Z00.6) and ≥1 claim with a Q modifier on or within 90 days after index date; and 2) without CTP: no claims with a CTP diagnosis or Q modifier. Patients with >1 primary cancer, T-cell therapy, or <360 days baseline or follow-up (unless death) enrollment were excluded. Biomarker testing, targeted therapy use, and healthcare costs per patient per month (PPPM) were assessed in the baseline period. Results: Of 61,490 patients identified, 1753 (3%) had CTP and 59,737 (97%) did not have CTP; 4% of commercial and 3% of MA patients had CTP. Most common tumor types were breast (27%; 2% had CTP), lung (16%; 3% had CTP), digestive tract (15%; 2% had CTP), and prostate (15%; 3% had CTP). Patients with CTP were younger and more frequently had documented biomarker test use in the baseline period than patients without CTP (Table). In unadjusted analyses, the CTP group had higher healthcare costs in the baseline period prior to CTP regardless of insurance type, driven by 51% higher systemic cancer therapy costs and 35% higher ambulatory visit costs. An ongoing propensity score matched analysis will evaluate the impact of CTP on cost of care in the follow-up period. Conclusions: Consistent with prior studies, the overall CTP rate among patients with advanced cancers was low (3%). Baseline costs (prior to CTP) were higher for patients that later enrolled in clinical trials than for patients without CTP. Further research is ongoing to assess differences in follow-up healthcare costs for patients with vs without CTP adjusting for baseline characteristics. [Table: see text]

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.

11175 Background: Biomarker testing informs treatment decisions by identifying patients who would clinically benefit from targeted regimens, leading to improved patient outcomes. However, the use of guideline-recommended biomarker testing in patients with advanced non-small cell lung cancer (NSCLC) is inconsistent. This study investigates the rates of biomarker testing in patients with NSCLC using a qualitative, real-world database. Methods: Natural language processing (NLP) was used to search and analyze the Amplity Insights database, consisting of transcribed, de-identified, records of physician-patient interactions obtained from patient medical records across the United States. This was a retrospective analysis of patients with a diagnosis of NSCLC (October 2003 - November 2023). Patient characteristics, biomarker testing, and treatment use were summarized and described. Results: 61,018 patients with NSCLC (mean [standard deviation] age of 69.8 [10.5] years) were identified. Among these, 50.6% were female and 87.9% identified as white. Among records with staging information, 26.6% had early-stage disease (stage 0-II) and 73.4% had late stage (stage III-IV) disease. In total, 13.4% (n=8,151) of all patients received biomarker testing. 13.3% (n=879) and 22.4% (n=2,402) of patients with stage III and IV, respectively, had biomarker testing performed; rates were higher in patients who were receiving care from an oncologist (16.8%, 31.0%, respectively). Among patients who had a confirmed actionable mutation (n=6,387), 35.9% received an appropriately matched targeted therapy and 10.1% received a nonindicated targeted therapy without harboring the indicated mutation. Of these, 40.7%, 22.7%, and 37.7% of patients harbored EGFR or ALK mutations, or were PD-L1 positive, respectively, and 35.8%, 17.8%, and 40.2% received the appropriate indicated treatment, respectively, based on testing. ALK-, EGFR-, and PD-L1-targeted therapies were taken by 12.1%, 9.4%, and 1.9% of patients, respectively, without evidence of the indicated biomarkers. Conclusions: These findings suggest that biomarker testing may be underutilized and that many patients may not be benefitting from treatment with precision therapies, highlighting the need for additional educational strategies to optimize precision oncology and elevate patient outcomes.

Real-world patterns and sequences of targeted therapy use in chronic lymphocytic leukemia and small lymphocytic lymphoma in the United States: a longitudinal study

With increasing focus on novel targeted therapies for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), this longitudinal claims-based study evaluated real-world CLL/SLL treatment sequences, particularly sequential targeted therapy. Among patients with first-line (1 L) treatment in 2014-2017 (N = 2,612; median follow-up = 3 years), the most common 1 L treatment was chemoimmunotherapy (CIT; 44.6%), followed by CD20 (25.2%) and Bruton’s tyrosine kinase inhibitors (BTKi; 21.7%). Among those with 1 L in 2018-2021 (N = 4,534; median follow-up = 1 year), these were BTKi (45.5%), CD20 (20.4%), CIT (17.5%), and B-cell lymphoma 2 inhibitor (8.3%). In 2014-2017, the proportion of patients receiving sequential targeted therapy in the first 2 LOTs was 11.2% (80.2% was BTKi→BTKi); in 2018-2021, this proportion was 34.3% (66.4% was BTKi→BTKi). Over time, there was a substantial increase in targeted therapy use in 1 L and sequential targeted therapy, particularly with BTKi→BTKi. Future studies should assess clinical outcomes to determine optimal sequences for CLL/SLL and reasons for restarting BTKi.

Immuno-Molecular Targeted Therapy Use and Survival Benefit in Patients with Stage IVB Cervical Carcinoma in Commission on Cancer®-Accredited Facilities in the United States.

To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs. without IMT after applying propensity score analysis to balance the clinical covariates. There were 3164 evaluable patients, including 969 (31%) who were treated with IMT. The use of IMT increased from 11% in 2013 to 46% in 2019. Age, insurance, facility type, sites of distant metastasis, and type of first-line treatment were independently associated with using IMT. In propensity-score-balanced patients, the median survival was 18.6 vs. 13.1 months for with vs. without IMT (p < 0.001). The AHR was 0.72 (95% CI = 0.64-0.80) for adding IMT overall, 0.72 for IMT + CT, 0.66 for IMT + CT + EBRT, and 0.69 for IMT + CT + EBRT + ICBT. IMT-associated survival improvements were suggested in all subgroups by age, race/ethnicity, comorbidity score, facility type, tumor grade, tumor size, and site of metastasis. IMT was associated with a consistent survival benefit in real-world patients with stage IVB cervical cancer.

Association of Timely Comprehensive Genomic Profiling With Precision Oncology Treatment Use and Patient Outcomes in Advanced Non-Small-Cell Lung Cancer.

Timely biomarker testing remains out of reach for many patients with advanced non-small-cell lung cancer (aNSCLC). Here, we studied the quality-of-care implications of closing the gap in timely receipt of comprehensive genomic profiling (CGP) to inform first-line (1L) decisions. Using a real-world clinicogenomic database, we studied testing and 1L treatment patterns in aNSCLC after the approval of pembrolizumab in combination with pemetrexed and carboplatin (May 10, 2017). To estimate the association of timely CGP results with therapy selection and patient outcomes, we identified patients with no previous genomic testing beyond PD-L1 immunohistochemistry and dichotomized patients by whether CGP results were available before or after 1L therapy initiation. In total, 2,694 patients were included in the 1L therapy decision impact assessment. Timely CGP increased matched targeted therapy use by 14 percentage points (17% with CGP v 2.8% without) and precision immune checkpoint inhibitor (ICPI) use by 14 percentage points (18% with CGP v 3.9% without). Receipt of timely CGP resulted in an estimated 31 percentage point decrease in ICPI use among ALK/EGFR/RET/ROS1-positive patients at an expected per-patient reduction in ineffective ICPI therapy cost of $13,659.37 with timely CGP to inform 1L treatment selection. Patient benefit of CGP extended to real-world time to therapy discontinuation (median time to therapy discontinuation: 3.9 v 10 months [hazard ratio, HR, 0.54 [95% CI, 0.42 to 0.70]; P = 1.9E-06; adjusted hazard ratio [aHR], 0.50 [95% CI, 0.38 to 0.67]; P = 2.0E-06) in 1L driver-positive patients. This effect was not significant for real-world overall survival (median overall survival: 32 v 29 months [HR, 1.2 [95% CI, 0.84 to 1.67]; P = .33; aHR, 1.4 [95% CI, 0.92 to 1.99]; P = .12). Timely CGP is associated with the quality of patient care as measured by 1L matched targeted therapy use, time to therapy discontinuation, and avoidance of ineffective, costly ICPIs.

Biomarker Testing, Targeted Therapy and Clinical Trial Participation by Race Among Patients With Lung Cancer: A Real-World Medicaid Database Study

IntroductionBiomarker testing in oncology is fundamental for targeted therapy use and clinical trial participation. Factors contributing to previously identified racial disparities in biomarker testing remain unclear. This study investigated biomarker testing, clinical trial participation, and targeted therapy by race among patients with metastatic lung cancer with Medicaid coverage in the United States. MethodsThe Merative MarketScan Medicaid claims database was used for this study to identify patients diagnosed with having metastatic lung cancer between 2017 and 2019 with at least 121 days of follow-up. Racial differences in biomarker testing, clinical trial enrollment, and targeted therapy use were analyzed using chi-square/t tests followed by logistic regression for confounding covariates. ResultsA total of 3845 patients were eligible. A total of 970 (25.2%) patients included in this study were Black. Biomarker testing was observed among 57.0%, targeted therapy among 4.6%, and 2.6% of the study cohort had evidence of clinical trial participation. No significant disparities between Black and White races were identified. Younger age and metastatic disease at initial diagnosis were the strongest independent factors associated with increased biomarker testing. Biomarker testing was positively associated with targeted therapy use (OR = 1.69, p = 0.005). ConclusionsPatients with metastatic lung cancer with Medicaid coverage were found to have exceedingly low biomarker testing rates; only 57% had evidence of any biomarker testing. Although no consistent differences between Black and White races were identified, this study calls attention to care experienced by socioeconomically disadvantaged patients with metastatic lung cancer in the United States.

Real-World Patterns of Targeted Therapy Use in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma in the United States: A Longitudinal Study

Introduction: Clinical guidelines and practice have shifted toward increasing use of novel Bruton's tyrosine kinase inhibitors (BTKi) or B-cell lymphoma 2 inhibitor (BCL2i) for treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). To highlight recent changes in clinical practice, this study evaluated real-world treatment sequences, with a focus on sequential novel targeted therapy, among patients with CLL/SLL in the US over time. Methods: Adult patients with ≥2 medical claims for CLL/SLL diagnosis on distinct days and ≥1 claim for CLL/SLL therapy were identified in the Optum Clinformatics DataMart database (2014-2021). The index date was the date of initiation of the first observed line of therapy (LOT) following the first observed CLL/SLL diagnosis. The observation period spanned from index to the earliest of end of eligibility, data availability, or death. LOTs were identified using a claims-based algorithm adapted from published literature during the observation period. Each LOT spanned from the initiation of a new agent to discontinuation of all agents in the LOT (i.e., 90-day gap without any dispensing), a switch to another agent, or the addition of a new agent. The proportion of patients receiving sequential targeted therapy in the first 2 LOTs (i.e., BTKi/BCL2i as first-line [1L] and second-line [2L] treatments in any order) was described. For sequential BTKi in 1L and 2L, treatments were also described by agent (i.e., ibrutinib, acalabrutinib, zanubrutinib, and combinations thereof). To assess longitudinal patterns, Sankey plots were created for 2 temporal data cohorts: patients with a 1L in 2014-2017 and patients with a 1L in 2018-2021. Results: We identified 7,146 eligible patients, 40.6% female, median age 73 years, with a median follow-up of 2 years after 1L initiation. The most common 1L treatment was BTKi (36.8%), then chemoimmunotherapy (CIT; 27.4%), CD20 (22.2%), chemotherapy (7.6%), and BCL2i (5.4%). In the first 2 LOTs, 22.3% of patients had sequential targeted therapy, comprising 70.0% BTKi→BTKi (i.e., BTKi retreated), 23.8% BTKi→BCL2i, 3.6% BCL2i→BCL2i, and 2.6% BCL2i→BTKi. The most common BTKi sequences by agent were ibrutinib→ibrutinib (61.6%) and ibrutinib→acalabrutinib (28.4%). Among patients with a 1L in 2014-2017 (N=2,612; median follow-up=3 years; Figure A), the most common 1L treatment class was CIT (44.6%), followed by CD20 (25.2%), BTKi (21.7%), chemotherapy (7.6%), and BCL2i (0.3%). For those receiving a 2L treatment (N=905), the 3 most common treatment classes were BTKi (37.6%), CD20 (30.2%), and CIT (17.2%). The proportion of patients receiving sequential targeted therapy in the first 2 LOTs was 11.2%; among these patients, 80.2% had BTKi→BTKi; 17.8% had BTKi→BCL2i; 2.0% had BCL2i→BCL2i; and 0% had BCL2i→BTKi. The most common BTKi sequences by agent were ibrutinib→ibrutinib (81.5%) and ibrutinib→acalabrutinib (17.3%). Among patients with a 1L in 2018-2021 (N=4,534; median follow-up=1 year; Figure B), the most common 1L treatment class was BTKi (45.5%), followed by CD20 (20.4%), CIT (17.5%), BCL2i (8.3%), and chemotherapy (7.6%). For 2L (N=833), the 3 most common treatment classes were BTKi (40.9%), CD20 (24.4%), and BCL2i (14.9%). The proportion of patients receiving sequential targeted therapy in the first 2 LOTs was 34.3%, comprising 66.4% BTKi→BTKi; 25.9% BTKi→BCL2i; 4.2% BCL2i→BCL2i; and 3.5% BCL2i→BTKi). Among those receiving sequential BTKi, the most common sequences by agent were ibrutinib→ibrutinib (53.2%), ibrutinib→acalabrutinib (33.2%), and acalabrutinib→acalabrutinib (5.3%). Conclusions: This longitudinal real-world study found a substantial increase in patients with CLL/SLL receiving targeted therapies in 1L over time. In particular, the proportion receiving BTKi in 1L doubled in 2018-2021 relative to 2014-2017 and accounted for almost half of the recent 1L CLL/SLL initiations. A third of patients with 1L observed in 2018-2021 also received a targeted agent in 2L, relative to about 1 in 10 patients in 2014-2017, with BTKi→BTKi being the most common sequence. Surprisingly, patients who received a BTKi in 1L were more likely to receive a BTKi in 2L than they were to switch to a BCL2i. Future studies should assess clinical outcomes to determine optimal sequences for CLL/SLL as well as the reasons for re-treatment with BTKi.

Pan-Tumor Analytical Validation and Osimertinib Clinical Validation in EGFR Mutant Non–Small-Cell Lung Cancer, Supporting the First Next-Generation Sequencing Liquid Biopsy in Vitro Diagnostic

Comprehensive genotyping is necessary to identify therapy options for patients with advanced cancer; however, many cancers are not tested, partly because of tissue limitations. Next-generation sequencing (NGS) liquid biopsies overcome some limitations, but clinical validity is not established and adoption is limited. Herein, clinical bridging studies used pretreatment plasma samples and data from FLAURA (NCT02296125; n=441) and AURA3 (NCT02151981; n=450) pivotal studies to demonstrate clinical validity of Guardant360 CDx (NGS LBx) to identify patients with advanced EGFR mutant non-small-cell lung cancer who may benefit from osimertinib. The primary end point was progression-free survival (PFS). Patients with EGFR mutation as identified by NGS LBx had significant PFS benefit with first-line osimertinib over standard of care (15.2 versus 9.6 months; hazard ratio, 0.41; P<0.0001) and with later-line osimertinib over chemotherapy (8.3 versus 4.2 months; hazard ratio, 0.34; P<0.0001). PFS benefits were similar to the original trial cohorts selected by tissue-based EGFR testing. Analytical validation included accuracy, precision, limit of detection, and specificity. Analytical validity was established for EGFR mutation detection and pan-tumor profiling. Panel-wide limit of detection was 0.1% to 0.5%, with 98% to 100% per-sample specificity. Patients with EGFR mutant non-small-cell lung cancer by NGS LBx had improved PFS with osimertinib, confirming clinical validity. Analytical validity was established for guideline-recommended therapeutic targets across solid tumors. The resulting US Food and Drug Administration approval of NGS LBx demonstrated safety and effectiveness for its intended use and is expected to improve adherence to guideline-recommended targeted therapy use.

Determinants of targeted cancer therapy use in community oncology practice: a qualitative study using the Theoretical Domains Framework and Rummler-Brache process mapping

BackgroundPrecision medicine holds enormous potential to improve outcomes for cancer patients, offering improved rates of cancer control and quality of life. Not all patients who could benefit from targeted cancer therapy receive it, and some who may not benefit do receive targeted therapy. We sought to comprehensively identify determinants of targeted therapy use among community oncology programs, where most cancer patients receive their care.MethodsGuided by the Theoretical Domains Framework, we conducted semi-structured interviews with 24 community cancer care providers and mapped targeted therapy delivery across 11 cancer care delivery teams using a Rummler-Brache diagram. Transcripts were coded to the framework using template analysis, and inductive coding was used to identify key behaviors. Coding was revised until a consensus was reached.ResultsIntention to deliver precision medicine was high across all participants interviewed, who also reported untenable knowledge demands. We identified distinctly different teams, processes, and determinants for (1) genomic test ordering and (2) delivery of targeted therapies. A key determinant of molecular testing was role alignment. The dominant expectation for oncologists to order and interpret genomic tests is at odds with their role as treatment decision-makers’ and pathologists’ typical role to stage tumors. Programs in which pathologists considered genomic test ordering as part of their staging responsibilities reported high and timely testing rates. Determinants of treatment delivery were contingent on resources and ability to offset delivery costs, which low- volume programs could not do. Rural programs faced additional treatment delivery challenges.ConclusionsWe identified novel determinants of targeted therapy delivery that potentially could be addressed through role re-alignment. Standardized, pathology-initiated genomic testing may prove fruitful in ensuring patients eligible for targeted therapy are identified, even if the care they need cannot be delivered at small and rural sites which may have distinct challenges in treatment delivery. Incorporating behavior specification and Rummler-Brache process mapping with determinant analysis may extend its usefulness beyond the identification of the need for contextual adaptation.

Examining molecular testing practices and targeted therapy use in advanced/metastatic non-small cell lung cancer (mNSCLC): A quality improvement initiative across ten community cancer centers.

e21191 Background: A growing number of targeted therapy approvals for mNSCLC have dramatically increased requirements for molecular testing. Identifying and addressing real-world challenges mNSCLC care teams face due to resulting workflow shifts is essential to optimize patient outcomes. Methods: In March–September 2022, 126 health care professionals (HCPs) who treat NSCLC at 10 US community oncology clinics completed surveys assessing practice patterns, challenges, and confidence related to biomarker testing and targeted therapy use. HCPs (N = 105) participated in interdisciplinary audit and feedback (AF) sessions to examine clinical evidence and develop clinic-specific action plans to address identified gaps. Results: Participants represented the interprofessional NSCLC care team: medical oncologists (32%), pathologists (1%), radiation oncologists (1%), pulmonologists (2%), PCP/other physicians (5%), advanced practice professionals (22%), nurses (19%), and other HCPs (e.g. patient navigator, practice manager; [19%]). At the time of the program there were 9 NCCN-recommended biomarkers for mNSCLC. Less than half of HCPs reported regular testing for 4 of these biomarkers (Table 1). The majority of HCPs were somewhat (52%) or very/extremely (23%) likely to start treatment prior to receiving molecular testing results. Top reported barriers to integrating molecular diagnostics into routine practice were biopsy tissue availability/quality (45%) and determining whether to begin treatment prior to receipt of molecular testing results (43%). Gap-oriented clinic action plans aimed to improve communication between oncologists, pulmonologists, and pathologists to increase quality and efficiency of testing. A targeted therapy toolkit was developed with a panel of oncology and pathology experts and distributed to participants to address gaps in knowledge of testing practices and guidelines. HCP confidence in biomarker testing increased from 72% to 92% following the intervention. More HCPs correctly answered knowledge (43% pre-AF vs 61% post-AF) and competence (29% pre-AF vs 54% post-AF) questions following participation in the AF sessions. Conclusions: While molecular testing is critical for mNSCLC care, HCPs report sub-optimal rates of conducting testing prior to treatment and incorporating results into treatment planning. Here, we highlight an unmet need for improved interdisciplinary communication and coordination in mNSCLC care teams and an educational intervention strategy that can be used to improve HCP biomarker and targeted therapy use in mNSCLC. [Table: see text]

Ethnic disparities in biomarker testing and targeted therapy use in metastatic lung adenocarcinoma: A 2014-2021 analysis.

e21216 Background: Racial and ethnic disparities have been demonstrated to be widespread in lung cancer, including in the US. Despite insurance coverage for standard biomarker testing, testing rates remain low in minority populations. This work sought to analyze institutional data to assess whether there existed ethnic disparities in biomarker testing rates and receipt of targeted therapy between Hispanic/Latino and non-Hispanic/Latino patients of metastatic lung adenocarcinoma (mAdenoCa). Methods: A retrospective study was conducted and reported following ‘strengthening the reporting of observational studies in epidemiology’ (STROBE) guidelines. All Hispanic white and non-Hispanic white patients of mAdenoCa seen at our tertiary care institution in South Florida from 01/2014 to 12/2021 were identified and included through Guardian Research Network (GRN) platform. Socio-demographic, clinicopathological, and tumor molecular features along with treatment-related characteristics were analyzed via descriptive and comparative statistics. Results: A total of 268 mAdenoCa patients were included, of which 179 patients were Hispanic or Latino and 89 were not Hispanic or Latino. Biomarker testing data is reported in the table. Data of MET, KRASG12C, VKIRAS, and HER3 was not available in all cases. The unadjusted product-limit survival analysis indicated worse outcomes for Hispanic whites as compared to non-Hispanic counterparts. There were no differences found regarding targeted therapy use in either population. Conclusions: While metastatic lung adenocarcinoma patients at our center showed no differences in biomarker testing or targeted therapy use, the non-availability of data regarding several key mutations indicates a major dearth of testing. Future studies need to evaluate actionable strategies for improving the existing low testing rates in patients with mAdenoCa, particularly in racial and ethnic minorities. [Table: see text]

Impact on turnaround times (TAT) among non-squamous non-small cell lung cancer (NSCLC) patients across three time periods with varying biomarker testing techniques.

9085 Background: Biomarker testing and identification of actionable genomic alterations (AGAs) in NSCLC patients have led to targeted therapy use and improved outcomes, particularly in advanced stages. We sought to evaluate the impact of different testing paradigms on TAT, particularly with respect to treatment decision and time to initiation of treatment, across three time periods. Methods: A retrospective review of stage III or IV non-squamous NSCLC patients at the Princess Margaret Cancer Centre (Toronto, Canada) was conducted. Both de novo advanced and patients with metastatic progressions are included. Cohort 1 (C1; 01/2015 – 01/2017) underwent reflex EGFR (EntroGen) and ALK (5A4 immunohistochemistry, IHC) single gene testing. Cohort 2 (C2; 02/2017 – 09/2020) underwent reflex next generation sequencing (NGS; Trusight Tumor 15), ALK and ROS1 testing. Cohort 3 (C3; 10/2020 – 01/2022) underwent reflex comprehensive NGS (161 genes, Oncomine OCA v3). Descriptive statistics are presented, including AGAs found and TAT from biopsy to result sign-out, and treatment related TAT. Results: Three cohorts of stage III and IV patients were identified, with C1 having proportionally more females (60%), never smokers (42%) with adenocarcinomas (98%). More patients with AGA were identified using NGS with larger panels (42%, 41%, 57%, respectively across C1 – C3). However, there is a longer median time from first oncology visit to treatment (14, 22, 27 days, respectively across C1-C3), and longer biopsy to treatment TAT trended towards more comprehensive testing (34, 38, 40 days, respectively across C1 - C3) in stage IV patients. Conclusions: As more comprehensive biomarker testing became available, more AGAs are identified with an increase in TAT from biopsy to sign-out and treatment start. Despite our institutional policy of reflex testing, future endeavours will be focus on ways to reduce TAT. [Table: see text]

Brief Report: Severe Sotorasib-Related Hepatotoxicity and Non-Liver Adverse Events Associated With Sequential Anti–Programmed Cell Death (Ligand)1 and Sotorasib Therapy in KRASG12C-Mutant Lung Cancer

IntroductionSequential anti–programmed cell death protein 1 (PD-1) or anti–programmed death-ligand 1 (PD-L1) followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in NSCLC. KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti–PD-(L)1. This study was designed to address whether sequential anti–PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs. MethodsThis is a multicenter, retrospective study of consecutive advanced KRASG12C-mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (National Cancer Institute Common Classification Criteria for Adverse Events—Version 5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti–PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti–PD-(L)1 as last line of treatment before sotorasib initiation. ResultsWe identified 102 patients who received sotorasib, including 48 (47%) in the sequence group and 54 (53%) in the control group. Patients in the control group received an anti–PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti–PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in the sequence group compared with those in the control group (50% versus 13%, p < 0.001). Severe sotorasib-related AEs occurred in 24 patients (24 of 48, 50%) in the sequence group, and among them 16 (67%) experienced a severe sotorasib-related hepatotoxicity. Severe sotorasib-related hepatotoxicity was threefold more frequent in the sequence group compared with that in the control group (33% versus 11%, p = 0.006). No fatal sotorasib-related hepatotoxicity was reported. Non-liver severe sotorasib-related AEs were significantly more frequent in the sequence group (27% versus 4%, p < 0.001). Severe sotorasib-related AEs typically occurred in patients who received last anti–PD-(L)1 infusion within 30 days before sotorasib initiation. ConclusionsSequential anti–PD-(L)1 and sotorasib therapy are associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion.

Practice-Level Variation in Molecular Testing and Use of Targeted Therapy for Patients With Non–Small Cell Lung Cancer and Colorectal Cancer

All patients with newly diagnosed non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) should receive molecular testing to identify those who can benefit from targeted therapies. However, many patients do not receive recommended testing and targeted therapies. To compare rates of molecular testing and targeted therapy use by practice type and across practices. This cross-sectional study used 100% Medicare fee-for-service data from 2015 through 2019 to identify beneficiaries with new metastatic NSCLC or CRC diagnoses receiving systemic therapy and to assign patients to oncology practices. Hierarchical linear models were used to characterize variation by practice type and across practices. Data analysis was conducted from June 2019 to October 2022. Oncology practice providing care. Primary outcomes were rates of molecular testing and targeted therapy use for patients with NSCLC and CRC. Secondary outcomes were rates of multigene testing for NSCLC and CRC. There were 106 228 Medicare beneficiaries with incident NSCLC (31 521 [29.7%] aged 65-69 years; 50 348 [47.4%] female patients; 2269 [2.1%] Asian, 8282 [7.8%] Black, and 91 215 [85.9%] White patients) and 39 512 beneficiaries with incident CRC (14 045 [35.5%] aged 65-69 years; 17 518 [44.3%] female patients; 896 [2.3%] Asian, 3521 [8.9%] Black, and 32 753 [82.9%] White patients) between 2015 and 2019. Among these beneficiaries, 18 435 (12.9%) were treated at National Cancer Institute (NCI)-designated centers, 8187 (5.6%) were treated at other academic centers, and 94 329 (64.7%) were treated at independent oncology practices. Molecular testing rates increased from 74% to 85% for NSCLC and 45% to 65% for CRC. First-line targeted therapy use decreased from 12% to 8% among patients with NSCLC and was constant at 5% for patients with CRC. For NSCLC, molecular testing rates were similar across practice types while rates of multigene panel use (13.2%) and targeted therapy use (16.6%) were highest at NCI-designated cancer centers. For CRC, molecular testing rates were 3.8 (95% CI: 1.2-6.5), 3.3 (95% CI, 0.4-6.1), and 12.2 (95% CI, 9.1-15.3) percentage points lower at hospital-owned practices, large independent practices, and small independent practices, respectively. Rates of targeted therapy use for CRC were similar across practice types. After adjusting for patient characteristics, there was moderate variation in molecular testing and targeted therapy use across oncology practices. In this cross-sectional study of Medicare beneficiaries, molecular testing rates for NSCLC and CRC increased in recent years but remained lower than recommended levels. Rates of targeted therapy use decreased for NSCLC and remained stable for CRC. Variation across practices suggests that where a patient was treated may have affected access to recommended testing and efficacious treatments.

Molecular Profiling and Treatment Pattern Differences between Intrahepatic and Extrahepatic Cholangiocarcinoma.

Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies. This multi-center collaboration included patients with ICC or ECC treated at one of eight participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were two-sided. Among 1,039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early-stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%), (all p < 0.00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%), (all p < 0.001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months, p < 0.001). Patients with advanced ECC have low rates of molecular profiling, possibly in part due to insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.

Variation in Use of Lung Cancer Targeted Therapies Across State Medicaid Programs, 2020-2021

Targeted therapies for EGFR (OMIM 131550)- and ALK (OMIM 105590)-altered metastatic non-small cell lung cancer (NSCLC) substantially improve outcomes for some patients. However, use of these therapies is lower among Medicaid patients, and access to oncology care varies across state Medicaid programs. Evidence is lacking on how use of targeted therapies for metastatic NSCLC varies across state Medicaid programs. To characterize state-level variation in the use of targeted therapies among Medicaid patients with metastatic NSCLC and to describe factors associated with this variation. This cross-sectional study used publicly available data from the Medicaid Drug Utilization Database from 2020 and 2021 and peer-reviewed data on NSCLC incidence, the prevalence of EGFR and ALK alterations, and expected treatment durations to estimate expected use of targeted therapies for EGFR- and ALK-altered NSCLC in 33 states. State-specific Medicaid programs and state policies and characteristics. The primary outcome was the estimated proportion of person-time of Medicaid patients with EGFR- or ALK-altered NSCLC associated with receipt of targeted therapy in each state Medicaid program. Nested linear regression models examined associations between the observed variation and state policies and characteristics. There were an estimated 3461 person-years in which EGFR- and ALK-targeted therapies were indicated in 2020 and 2021. During these years, only 2281 person-years of EGFR- and ALK-targeted therapies were dispensed to Medicaid patients, suggesting that an estimated 66% of Medicaid patients with EGFR- and ALK-altered metastatic disease received indicated targeted therapies across all states. Rates of targeted therapy use ranged from 18% in Arkansas to 113% in Massachusetts; 30 of 33 states (91%) had lower rates of targeted therapy use than expected. The observed variation across state Medicaid programs was associated with Medicaid policies, the density of oncologists, and state gross domestic product per capita. This study suggests that rates of targeted therapy use among Medicaid patients with EGFR- and ALK-altered NSCLC were lower than expected and varied across state Medicaid programs. State policies and characteristics were associated with the observed variation, indicating where interventions could improve access to treatment and outcomes for patients with NSCLC.

1151P Evolution of biomarker testing among non-squamous/non-small cell lung cancer (NSCLC) patients (Pts) and impact on turnaround times (TAT)

Biomarker testing and identification of actionable genomic alterations (AGA) in NSCLC pts has led to targeted therapy use and improved outcomes. As testing methods evolve, we sought to characterize the impact of different testing paradigms on TAT.

Variation of use of targeted therapies and molecular diagnostic testing by practice type for non-small cell lung cancer and colorectal cancer.

6551 Background: Targeted therapies are important first-line treatments for many patients with non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). All patients with newly-diagnosed metastatic NSCLC and CRC should undergo molecular diagnostic testing to guide treatment selection. Methods: We used 100% Medicare fee-for-service data from 2015 through 2019 to identify beneficiaries with incident metastatic NSCLC or CRC receiving systemic therapy and to assign beneficiaries to oncology practices. We then assessed for use of molecular diagnostic testing and targeted therapies in these cohorts. We used linear mixed effects models to assess patient and practice characteristics associated with molecular diagnostic testing and targeted therapy use. Results: Rates of molecular diagnostic testing increased between 2015 and 2019 for NSCLC and CRC. In 2019, rates of molecular diagnostic testing were 85% and 65% for NSCLC and CRC, respectively. Rates of targeted therapy use did not increase over time for NSCLC or CRC, and were 8% and 5%, respectively, in 2019. Compared to National Cancer Institute (NCI)-designated cancer centers, rates of molecular diagnostic testing for CRC were 3.7 percentage points lower at practices associated with non-academic hospitals and 10.6 percentage points lower at small independent practices. Rates of targeted therapy use for NSCLC were 4.8, 5.9 and 5.5 percentage points lower at academic medical centers, large independent practices and small independent practices, respectively, compared to NCI centers. Conclusions: Rates of molecular diagnostic testing for NSCLC and CRC increased in recent years, but testing rates remain below recommended levels, and targeted therapy use remains low. Substantial variation in testing and targeted therapy use by practice type suggest that the practice where a patient is treated may impact access to recommended testing and efficacious treatments. [Table: see text]