Real-World Treatments and Clinical Outcomes in Advanced NSCLC without Actionable Mutations after Introduction of Immunotherapy in Japan

SIMPLE SUMMARY: The aim of this study was to evaluate treatment patterns and real-world clinical outcomes since immunotherapy was introduced in Japan as the initial (first-line) therapy for treating patients with lung cancer, the leading cause of cancer-related deaths in Japan. For 1182 patients with advanced non-small-cell lung cancer, the survival rate at two years after starting first-line therapy was 40% with platinum doublet chemotherapy, 58% with immunotherapy, and 31% with nonplatinum regimens. The results of this large study enabled us to describe the characteristics of a real-world patient population, together with the treatment patterns for advanced non-small-cell lung cancer and clinical outcomes from real-world settings, where most patients receive treatment. Most first-line therapies were administered in accordance with contemporaneous national treatment guidelines, and the study findings indicate improvement in real-world clinical outcomes for patients with advanced non-small-cell lung cancer since the introduction of first-line immunotherapy. ABSTRACT: The aims of this study were to describe systemic treatment patterns and clinical outcomes for unresectable advanced/metastatic non-small-cell lung cancer (NSCLC) by first-line regimen type in real-world clinical settings in Japan after the introduction of first-line immune checkpoint inhibitor (ICI) monotherapy in 2017. Using retrospective chart review at 23 study sites, we identified patients ≥20 years old initiating first-line systemic therapy from 1 July 2017 to 20 December 2018, for unresectable stage IIIB/C or IV NSCLC; the data cutoff was 30 September 2019. Eligible patients had recorded programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) and no known actionable EGFR/ALK/ROS1/BRAF genomic alteration. Kaplan-Meier method was used to determine time-to-event endpoints. Of 1208 patients, 647 patients (54%) received platinum doublet, 463 (38%) received ICI monotherapy, and 98 (8%) received nonplatinum cytotoxic regimen as first-line therapy. PD-L1 TPS was ≥50%, 1–49% and <1% for 44%, 30%, and 25% of patients, respectively. Most patients with PD-L1 TPS ≥50% received ICI monotherapy (453/529; 86%). Excluding 26 patients with ECOG performance status of 3–4 from outcome analyses, the median patient follow-up was 11.3 months. With first-line platinum doublet, ICI monotherapy, and nonplatinum cytotoxic regimens, median overall survival (OS) was 16.3 months (95% CI, 14.0–20.1 months), not reached, and 14.4 months (95% CI, 10.3–21.2 months), respectively; 24-month OS was 40%, 58%, and 31%, respectively. Differences in OS relative to historical cohort data reported in Japan are consistent with improvement over time in real-world clinical outcomes for advanced NSCLC.