First-line nivolumab plus ipilimumab with or without chemotherapy for Japanese patients with non-small cell lung cancer: LIGHT-NING study

Abstract

Objective: As first-line treatment for stage IV or recurrent non-small cell lung cancer, combination immunotherapy with nivolumab and ipilimumab, with or without chemotherapy, had demonstrated survival benefits over chemotherapy; however, data on Japanese patients are limited.

Methods: LIGHT-NING was a multicenter, observational study and retrospectively collected data. In this interim analysis, we analyzed patients who received combination immunotherapy between 27 November 2020 and 31 August 2021 for the treatment status, safety objectives (treatment-related adverse events and immune-related adverse events incidences), and effectiveness objectives (objective response rate and progression-free survival) to determine the characteristics and early safety information.

Results: We analyzed 353 patients, with a median follow-up of 7.1 (interquartile range, 5.0-9.7) months. Overall, 60.1 and 39.9% received nivolumab plus ipilimumab with and without chemotherapy, respectively. In these cohorts, the median age was 67 and 72 years; 10.8 and 35.5% were aged ≥75 years; 80.2 and 79.4% were male; 5.2 and 13.5% had a performance score ≥ 2; 32.1 and 27.0% developed grade 3-4 immune-related adverse events; treatment-related deaths were observed in 6 (2.8%) and 5 (3.5%) patients, respectively. Grade 3-4 immune-related adverse event incidence was the highest within the first month of treatment in both cohorts, although the immune-related adverse event risk persisted throughout. No new safety signals were observed at this interim analysis. The median progression-free survival was 6.0 (95% confidence interval, 5.2-7.6) and 5.8 (4.3-7.0) months in nivolumab plus ipilimumab with and without chemotherapy cohorts, respectively.

Conclusions: LIGHT-NING offers valuable insights into combination immunotherapy for untreated patients with stage IV or recurrent non-small cell lung cancer in Japanese real-world settings.

Keywords: Japan; ipilimumab; nivolumab; non-small-cell lung carcinoma; observational study.

Figure 1

Proportion of patients who developed CTCAE grade 3–4 irAEs or TRAEs leading to discontinuation over time. Proportions of patients who developed at least one irAE for which the worst grade was 3–4 within each time interval in the nivolumab plus ipilimumab with (A) and without (B) chemotherapy cohorts. The proportion of patients who developed at least one TRAE leading to treatment discontinuation within each time interval in the nivolumab plus ipilimumab with (C) and without (D) chemotherapy cohorts. CTCAE, Common Terminology Criteria for Adverse Events Grading System; irAE, immune-related adverse event; TRAE, treatment-related adverse event.

Figure 2

Time to onset of CTCAE grade ≥ 3 irAEs. Time from treatment initiation to onset of CTCAE grade ≥ 3 irAEs in the nivolumab plus ipilimumab with (A) and without (B) chemotherapy cohorts. The figures show grade ≥ 3 irAEs with an incidence of ≥1% in both cohorts. Vertical lines indicate the median to onset. Time to onset of an irAE was defined as the time from the initiation of treatment to the onset of an irAE for which the worst grade was ≥ 3. CTCAE, Common Terminology Criteria for Adverse Events Grading System; irAE, immune-related adverse event.

Figure 3

Kaplan–Meier analysis of PFS in the nivolumab plus ipilimumab with chemotherapy cohort. Kaplan–Meier analysis of PFS in the nivolumab plus ipilimumab with chemotherapy cohort (A) and that according to tumor PD-L1 expression levels of two categories (<1 and ≥1%) (B). CI, confidence interval; NE, not estimated; PD-L1, programmed death ligand 1; PFS, progression-free survival.

Figure 4

Kaplan–Meier analysis of PFS in the nivolumab plus ipilimumab cohort. Kaplan–Meier analysis of PFS in the nivolumab plus ipilimumab cohort (A) and that according to tumor PD-L1 expression levels of two categories (<1 and ≥1%) (B). CI, confidence interval; PD-L1, programmed death ligand 1; PFS, progression-free survival.