Abstract
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.