Gene mutations according to poverty level and RUCA codes

Description of rural-urban commuting area (RUCA) codes

COXPH model for patients with at least 6-mo overall survival

OBJECTIVES:Novel first-line (1L) combination regimens offer improved efficacy for patients with epidermal growth factor receptor-mutated (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) versus the standard of care, but their costs have not been comprehensively evaluated. Total and differential costs of 1L osimertinib plus platinum-pemetrexed, intravenous (IV) amivantamab plus lazertinib, and subcutaneous (SC) amivantamab plus lazertinib were estimated from a United States (US) payer perspective. METHODS:A cost of care model was developed to assess treatment acquisition, administration, disease management, and adverse event (AE) management costs for osimertinib plus platinum-pemetrexed versus IV and SC amivantamab plus lazertinib for patients with EGFRm NSCLC. A one-year time horizon was chosen to allow for direct treatment comparison; a one-year treatment duration was assumed for treat-to-progression regimen components. RESULTS:The total first-year cost per-patient for osimertinib plus platinum-pemetrexed (all-payer perspective: $172,600; private perspective: $253,529; Medicare perspective: $84,926) was over twofold lower than for IV amivantamab plus lazertinib (all-payer perspective: $418,176; private perspective: $618,240; Medicare perspective: $201,441) and for SC amivantamab plus lazertinib (all-payer perspective: $419,718; private perspective: $621,166; Medicare perspective: $201,482). This translated to per-patient cost savings of $245,577; $364,711; and $116,514 for osimertinib plus platinum-pemetrexed versus IV amivantamab plus lazertinib and $247,118; $367,637; and $116,555 versus SC amivantamab plus lazertinib for the all-payer, private, and Medicare perspectives, respectively. LIMITATIONS:Limited data availability necessitated cost conversions across payer perspectives and assumptions for select inputs, including specific concomitant medication durations. Additionally, as any payer-negotiated discounts for treatment are confidential, model treatment acquisition costs reflected list prices. These data limitations contributed to uncertainty surrounding model inputs. CONCLUSIONS:From a US payer perspective, osimertinib plus platinum-pemetrexed was associated with substantially lower overall costs compared with IV and SC amivantamab plus lazertinib for the 1L treatment of patients with EGFRm locally advanced or metastatic NSCLC.

Overall survival by RUCA code and poverty

Overall survival by RUCA code and poverty

Prevalence of common mutations in tumor subtypes

Overall survival of cohort by stage

COXPH model for patients with stage information

Comparison of Caris cohort data with Puckrein dataset

Comparison of overall survival among chemotherapy-treated TP53-mutated and TP53-wild type patients in Caris CODEai clinico-genomic database

Copy number alterations (CNAs) and fusions among cohort

Genomic features and clinico-demographic associations of cohort. A, Total number of tumors positive for each mutated gene. B, Percentage of total tumors from each study site for the top 20 most commonly mutated genes. C, Prevalence of co-mutations among APC, EGFR, STK11, TP53, and KRAS. Red indicates strong co-mutation whereas blue indicates mutual exclusivity. D, Percentage of indicated tumor types with mutations in APC, EGFR, STK11, TP53, and KRAS. E, Age of patients among (−) and (+) gene mutation cohorts. The red line indicates the median age. F, Ratio of males to females in (−) and (+) gene mutation cohorts. G, Percentage of total (−) and (+) cohorts composed by indicated racial groups. *, P < 0.05; **, P < 0.01; #, P < 0.001; ns, not significant.

Tumor lineages of the cohort and analysis of OS by race. A, Total numbers of each tumor type broken down by study site. B, Percentage of the total made up by each study site for the top 10 most represented tumor types. C, Kaplan–Meier curve for OS of White patients (black line) and Black patients (red line) among molecularly-tested cohort. D, COXPH analyzing the effect of race on OS in individual tumor types. *, P < 0.05. E and F, Median survival among the Caris cohort (E) or 5-year survival among the SEER cohort (F) was plotted for male and female White and non-White patients in three different age groups (<50 years; 50 ≤ years < 65; and ≥65).

Health disparities present a barrier to successful oncology treatment. The potential for precision oncology to reduce health disparities has not previously been analyzed. We performed a retrospective analysis of 12,627 patients from six major cancer centers whose tumors underwent molecular testing at Caris Life Sciences between 2010 and 2020. Kaplan-Meier and Cox regression were used to describe and analyze overall survival. The molecular and demographic features of the cohort were analyzed by chi 2 and ANOVA tests. Black patients composed 25% of the cohort and White patients 63%. Among this molecularly-tested cohort, there were minimal outcome differences based on race, geographic location, or poverty level. When analyzing the interaction of age, race, and sex, racial-based disparities were noted primarily for young non-White women in the study cohort but were more pronounced for men and women of all ages in the broader patient population within the Surveillance, Epidemiology, and End Results database. Mutations in five genes-APC, EGFR, STK11, TP53, and KRAS-were found to affect overall survival among our cohort, and their prevalence varied by race in specific tumor types. Real-world outcomes data in mutation-defined cohorts also provided additional context to previously reported therapeutic response trends. Our study shows that patients who undergo molecular testing display reduced racial health disparities compared with the general population, whereas persistent racial disparities are influenced by age and sex. Genomic-driven racial disparities should be examined at a tumor lineage-specific level. Increased access to molecular testing for all eligible patients may play a role in improving health equity.Significance: This study is the largest of its kind to analyze health disparities and genomic features among a diverse multiinstitutional cohort of patients who underwent molecular testing. Continuing to increase awareness of and access to molecular testing approaches may help to reduce cancer health disparities and improve outcomes for all patients.