Real-world evidence on changes in uptake, sepsis, and costs with dual immunotherapy for first-line NSCLC.

Abstract

e20701 Background: The addition of immunotherapy to platinum-based chemotherapy regimens has transformed first-line treatment of non-small cell lung cancer (NSCLC), as demonstrated by KEYNOTE-407. Subsequently, CHECKMATE 9LA showed improved overall survival (OS) with a tolerable safety profile when dual immunotherapy was combined with chemotherapy. This study aimed to provide comprehensive real-world evidence on the utilization, adverse events, and healthcare costs associated with first-line chemo-immunotherapy regimens compared to non-immunotherapy regimens in NSCLC. Methods: We conducted a retrospective analysis of the Highmark claims database from January 2020 through May 2025. Adult patients diagnosed with NSCLC of any stage who initiated first-line chemotherapy with either singlet immunotherapy, doublet immunotherapy, or no immunotherapy were included. Key outcomes assessed included time to treatment discontinuation (TTD), incidence of adverse events (AEs), healthcare costs estimated as per-member-per-month (PMPM), and overall survival (OS) determined from recorded deaths. Results: A total of 3,117 patients met inclusion criteria: 1,560 (50.0%) received chemotherapy alone, 957 (30.7%) received chemotherapy with singlet immunotherapy, 37 (1.2%) received chemotherapy with doublet immunotherapy, and 563 (18.1%) received other regimens. Median TTD was 96 days [IQR 55-143] for chemotherapy only, 93 [IQR 51-134] days for chemotherapy with singlet immunotherapy, and a notably shorter 55 [IQR 49-68] days for chemotherapy used with doublet immunotherapy. PMPM cost increased significantly at follow-up for all patients, with patients receiving chemotherapy and doublet immunotherapy seeing the largest increase from $6,895 at baseline to $75,348 at follow-up. Adverse events were similar across all arms; however, sepsis occurred more frequently in the doublet immunotherapy group (18.9%) compared with the singlet immunotherapy group (7.4%) or the chemotherapy alone group (8.9%). Among 945 patients with recorded deaths, 1- and 3- year OS rates were 79.2% and 58.8% for chemotherapy alone, 73.8% and 44.0% for the singlet immunotherapy arm, and 74.9% and 62.4% for the doublet immunotherapy arm, respectively. Conclusions: This real-world analysis reveals a substantial gap between clinical trial data and routine clinical practice for first-line NSCLC treatment. Dual immunotherapy regimens were remarkably underutilized, associated with an increased incidence of sepsis, and incurred significantly higher healthcare costs. While acknowledging the limitations of a retrospective, claims-based study, these findings underscore critical real-world challenges related to utilization, safety, and economic burden. These insights are vital for informing treatment guidelines, payer policies, and future research to optimize value-based care in NSCLC.