Regimen selection for combined immunotherapy in non-small cell lung cancer with PD-L1 < 1%: a multicenter, retrospective study from Japan (SPIRAL-LT1)

This multicenter retrospective study at 22 centers in Japan using electronic medical record data aimed to compare the effectiveness and safety of CTLA-4 regimens (ipilimumab plus nivolumab with or without chemotherapy) versus non-CTLA-4 regimens (pembrolizumab or atezolizumab plus chemotherapy) as first-line treatment for patients with advanced or recurrent NSCLC expressing PD-L1 < 1%. Dual primary endpoints were PFS and OS after propensity score matching (PSM) incorporating age, gender, PS, stage, histology, driver mutations, smoking, liver metastasis, and brain metastasis. Safety was assessed by the incidence and onset timing of ≥ grade 3 drug-related AEs. A total of 124 patients each were analyzed for both regimens. PFS and OS did not differ between CTLA-4 and non-CTLA-4 regimens, and exploratory subgroup analyses showed no substantial differences in treatment effect across patient characteristics. The CTLA-4 regimen had a higher incidence of ≥ grade 3 irAEs, particularly hepatic and gastrointestinal disease, and a lower incidence of ≥ grade 3 chemo-AEs. Onset of grade ≥ 3 irAEs also differed between regimens, and late-onset events with CTLA-4 regimens showed longer OS. In conclusion, while first-line CTLA-4 and non-CTLA-4 regimens showed comparable effectiveness in patients with NSCLC expressing PD-L1 < 1%, distinct toxicity profiles were observed, suggesting careful consideration of safety profiles is warranted.