Discussion
NSCLC, tumor, cancers, melanoma, TRAEs
TUMOR, CANCERS, MELANOMA, EVENT, DISEASE, NSCLC
The results of this subanalysis in Japanese patients from the CheckMate 227 Part 1 study represent the longest survival follow-up reported to date for phase 3 studies evaluating first-line combination immunotherapy for metastatic NSCLC with tumor PD-L1 ≥ 1% or < 1%. With a 5-year minimum follow-up, clinically meaningful OS benefit was maintained with nivolumab plus ipilimumab versus chemotherapy in Japanese patients regardless of tumor PD-L1 expression, despite a high rate of subsequent immunotherapy received in the chemotherapy arm (81%) in the combined PD-L1 ≥ 1% and < 1% population of patients with a PFS event. The results were consistent with the 3-year follow-up analysis in Japanese patients [PFS and DOR benefit was maintained with nivolumab plus ipilimumab at 5 years. Additionally, patients in the combined PD-L1 ≥ 1% and < 1% population who were alive at 5 years had a higher 3-year TFI rate with nivolumab plus ipilimumab versus chemotherapy, with 59% versus 15% of patients receiving no subsequent systemic therapy at the 5-year time point, suggesting the long-term durable benefit of this first-line immunotherapy combination in Japanese patients. Among patients who discontinued nivolumab plus ipilimumab treatment within 2 years due to TRAEs, 58% remained alive for ≥ 5 years, with 47% of patients receiving no subsequent therapy within 3 years of discontinuation.Recent studies in melanoma and other cancers have demonstrated that TFI, during which patients typically experience clinically stable disease while remaining treatment-free, is associated with improved quality of life [No new safety signals were reported in this subanalysis after long-term follow-up (≥ 5 years). TRAEs reported in Japanese patients at 5 years were consistent with the 3-year data [This exploratory subanalysis was not statistically powered to conduct statistical testing for comparisons between treatment arms. The subanalysis was also limited by small sample sizes for the patient subgroups. The findings in Japanese patients, however, were consistent with results in the randomized global population and aligned with findings from other immunotherapy-based treatments in this subpopulation [In conclusion, at ≥ 5-year follow-up, first-line nivolumab plus ipilimumab provided long-term efficacy benefits versus chemotherapy in Japanese patients with metastatic NSCLC, regardless of tumor PD-L1 expression. Consistent with the long-term findings in the randomized global population, these data continue to support the use of nivolumab plus ipilimumab as first-line treatment for patients with metastatic NSCLC in Japan.