Efficacy of ipilimumab plus nivolumab with or without chemotherapy according to baseline tumor size: a multicenter retrospective study

Background: Ipilimumab plus nivolumab (I-N) with or without chemotherapy is an established first-line treatment for advanced non-small cell lung cancer (NSCLC). For patients with a large baseline tumor size (BTS), chemotherapy combined with immune checkpoint inhibitors (ICIs) has shown better outcomes compared with ICI monotherapy. However, the specific radiographic size criteria for determining whether to prioritize the CheckMate227 or CheckMate9LA regimen are undefined. Therefore, we evaluated how BTS impacts the efficacy of I-N-based therapy in our cohort.

Methods: This multicenter retrospective study was conducted across 19 institutions in Japan. Adult patients with advanced NSCLC with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) 1–49% who received I-N-based therapy as first-line systemic treatment between January 2018 and March 2022 were included. We excluded patients with EGFR or ALK mutation. Patients were classified into two groups: the I-N group and the I-N-chemo group. Survival outcomes were evaluated based on BTS (≥50 vs. <50 mm). Baseline covariates were obtained from medical records.

Results: A total of 87 patients were included: 25 in the I-N group and 62 in the I-N-chemo group. Among patients with BTS ≥50 mm, median progression-free survival (PFS) was 4.0 months [95% confidence interval (CI): 0.7–6.7] in the I-N group and 5.5 months (95% CI: 3.4–8.1) in the I-N-chemo group (P=0.03). Median overall survival (OS) was 8.3 months (95% CI: 1.0–10.7) for I-N and 17.7 months (95% CI: 10.9–not reached) for I-N-chemo (P=0.005). Among patients with BTS <50 mm, there were no statistically significant differences in PFS or OS between the I-N and I-N-chemo groups.

Conclusions: Our findings suggest that I-N combined with chemotherapy may be effective treatment for NSCLC patients with a high tumor burden (BTS ≥50 mm). However, given the retrospective nature of this study and the limited subgroup sample sizes, these results should be interpreted with caution.