Real-World Treatment Patterns and Outcomes of First-Line Immunotherapy Among Patients With Advanced Nonsquamous NSCLC Harboring BRAF, MET, or HER2 Alterations

Marina C Garassino; Sabine Oskar; Ashwini Arunachalam; Ke Zu; Yu-Han Kao; Cai Chen; Weilin Meng; M Catherine Pietanza; Bin Zhao; Himani Aggarwal

doi:10.1016/j.jtocrr.2023.100568

Real-World Treatment Patterns and Outcomes of First-Line Immunotherapy Among Patients With Advanced Nonsquamous NSCLC Harboring BRAF, MET, or HER2 Alterations

JTO Clin Res Rep. 2023 Aug 23;4(10):100568. doi: 10.1016/j.jtocrr.2023.100568. eCollection 2023 Oct.

Authors

Affiliations

¹ Thoracic Oncology Program, Section of Hematology Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois.
² Center for Observational and Real-World Evidence (CORE), Merck & Co., Inc., Rahway, New Jersey.
³ Epidemiology, Merck & Co., Inc., Rahway, New Jersey.
⁴ Data, AI and Genome Sciences (DAGS) Department, Merck & Co., Inc., Rahway, New Jersey.
⁵ Clinical Research, Merck & Co., Inc., Rahway, New Jersey.

Abstract

Introduction: Data on utilization and clinical outcomes of programmed cell death protein or programmed death-ligand 1 (PD-[L]1) inhibitors in NSCLC with uncommon oncogenic alterations is limited.

Methods: This retrospective study used a deidentified U.S. nationwide clinicogenomic database to select patients with advanced nonsquamous NSCLC without EGFR, ALK, or ROS1 alterations, diagnosed from January 1, 2016 to September 30, 2020, who initiated first-line therapy. Our objectives were to summarize characteristics and treatment patterns for patients with four little-studied genomic alterations or driver-negative NSCLC. We estimated Kaplan-Meier real-world time on treatment (rwTOT) and time to next treatment for patients receiving PD-(L)1 inhibitors. The data cutoff was September 30, 2021.

Results: Of the 3971 eligible patients, 84 (2%) had NSCLC with BRAF V600E mutation, 117 (3%) had MET exon 14 skipping mutation, 130 (3%) had MET amplification, 91 (2%) had ERBB2 activation mutation, and 691 patients (17%) had driver-negative NSCLC. Patient characteristics differed among cohorts as expected. The most common first-line regimen in each cohort was a PD-(L)1 inhibitor as monotherapy or in combination with chemotherapy. The median rwTOT with anti-PD-(L)1 monotherapy was 4.6 months in the driver-negative cohort and ranged from 2.9 months (ERBB2 mutation) to 7.6 months (BRAF V600E mutation). The median rwTOT with anti-PD-(L)1-chemotherapy combination was 5.2 months in the driver-negative cohort and 6 months in all but the BRAF V600E cohort (17.5 mo). The patterns of real-world time to next treatment results were similar.

Conclusions: Substantial use of anti-PD-(L)1 therapy and associated clinical outcomes are consistent with previous real-world findings and suggest no detriment from PD-(L)1 inhibitors for advanced nonsquamous NSCLC harboring one of these four genomic alterations relative to driver-negative NSCLC.

Keywords: Advanced non–small cell lung cancer; Genomic alterations; Immunotherapy; Real-world time on treatment; Real-world time to next treatment.