Real-World Outcomes and Early Progressive Disease Analysis of Nivolumab and Ipilimumab Combination Therapy in Metastatic NSCLC: LIGHT-NING Study 2.5-year update

Background First-line nivolumab plus ipilimumab with/without two cycles of chemotherapy has been approved for untreated metastatic non-small cell lung cancer (NSCLC) in Japan, based on CheckMate 9LA and CheckMate 227, but long-term real-world data in Japanese patients are limited. Methods LIGHT-NING is an ongoing, multicenter, observational study, examining nivolumab plus ipilimumab, with/without chemotherapy for patients with stage IV or recurrent NSCLC. We assessed treatment patterns, effectiveness, and safety, using 2.5-year data from November 2020 to June 2024. Exploratory analyses characterized early progressive disease (PD) and associated baseline factors. These analyses were hypothesis-generating in nature. Results Of 545 patients (median age: 70 years, 18.9% female, 89.9% Eastern Cooperative Oncology Group performance status of 0–1, median follow-up period 15.1 months), 319 (58.5%) received nivolumab plus ipilimumab with chemotherapy and 226 (41.5%) without chemotherapy. Median overall survival and real-world progression-free survival were 21.7 and 6.8 months, respectively, in patients with chemotherapy, and 18.8 and 6.3 months, respectively, without chemotherapy. Grade 3–5 treatment-related adverse events occurred in 170 (53.3%) and 69 (30.5%) patients, respectively. As an exploratory analysis, early PD in the cohort without chemotherapy was associated with body mass index (BMI) in squamous cell carcinoma and albumin (ALB), lactate dehydrogenase (LDH), and lung immune prognostic index (LIPI) in non-squamous cell carcinoma. Conclusions This analysis of LIGHT-NING study indicated that safety and effectiveness in Japanese patients were consistent with those observed in CheckMate 9LA and CheckMate 227. No new safety signals were observed, the combination therapy was generally well manageable. Micro‑Abstract This real‑world analysis of the LIGHT-NING study assessed nivolumab plus ipilimumab with or without chemotherapy in 545 Japanese patients with metastatic or recurrent NSCLC. Using 2.5‑year data, overall survival and real-world progression-free survival were consistent with outcomes reported in CheckMate 9LA and CheckMate 227, with no new safety signals observed. These real‑world data from Japan suggest that nivolumab plus ipilimumab, with or without chemotherapy, provides survival benefit for patients with NSCLC.