Long‐Term Outcomes and Toxicities in Patients With Metastatic Non‐Small Cell Lung Cancer Treated With Immunotherapy Containing Regimens

Introduction Immunotherapy is well‐established in treating metastatic non‐small cell lung cancer (mNSCLC); however, data regarding acquired resistance and long‐term outcomes are limited. We examined long‐term outcomes in mNSCLC patients with ongoing treatment response at 2 years (long‐term responders) post‐treatment commencement. Methods This multi‐center retrospective study identified mNSCLC patients treated with first‐ or second‐line immunotherapy±chemotherapy. Endpoints included progression‐free survival (PFS) and overall survival (OS), stratified by PD‐L1 tumor proportion score (TPS) (< 50% vs. ≥ 50%), treatment duration, and treatment line. Results Of 354 patients, 52 (15%) long‐term responders were identified for analysis. Among them, median age was 68.5 years (28–87); the majority had an ECOG performance status ≤ 1 (81%), high‐PD‐L1 TPS (52%), and adenocarcinoma histopathology (83%). Most (73%) received immunotherapy first‐line. Median treatment duration was 23.5 months (1–80), and 19% prematurely ceased treatment. With a median follow‐up of 39 months from treatment commencement (95% CI 37–49), 15 (29%) patients had progressive disease, and 3‐year PFS was 78%. Oligo‐progression was common (87%), with lung/pleural disease (53%). Most received subsequent treatment (local therapy alone: 53%, systemic therapy alone: 20%, combined: 20%, supportive care: 7%) and achieved disease control (86%). Long‐term toxicities occurred in 44% and were predominantly endocrinopathies (83%) requiring ongoing management. Three‐year OS was 93%. Survival outcomes were unaffected by treatment duration, PD‐L1 TPS, and treatment line. Conclusions Long‐term responders showed favorable survival outcomes, with most maintaining disease control with local therapies even after progression. This held true regardless of treatment duration, PD‐L1 TPS, or treatment line. Endocrinopathies were common long‐term toxicities.