First-Line Camrelizumab versus Placebo Plus Chemotherapy with or without Radiotherapy for Brain Metastases in Non-Small-Cell Lung Cancer: The CTONG 2003 Randomized Placebo-Controlled Trial.

Abstract

Introduction: Retrospective studies have indicated potential benefits of immunotherapy for brain metastases (BM) in non-small-cell lung cancer (NSCLC). CTONG 2003 is the first randomized controlled trial to evaluate camrelizumab for untreated BM of NSCLC.

Methods: CTONG 2003 is a multicenter, randomized, double-blind, placebo-controlled trial. Treatment-naïve NSCLC with BM, negative for EGFR mutations and ALK fusions, were randomized 1:1 to receive either camrelizumab or placebo, plus platinum-doublet chemotherapy for 4-6 cycles, followed by maintenance therapy with camrelizumab or placebo ± pemetrexed for up to 31 cycles. Radiotherapy was administered for BM, if necessary, within 42 days of the first treatment dose. The co-primary endpoints were intracranial progression-free survival (iPFS) and PFS. Planned enrollment was 200 patients, but recruitment was terminated early due to therapeutic paradigm shifts globally.

Results: Between May 28, 2021, and July 21, 2023, 60 patients were randomized, with 32 assigned to the camrelizumab group and 28 to the placebo group. The median iPFS was 12.7 months (95% CI: 7.1-25.3) for camrelizumab versus 9.9 months (95% CI: 6.3-14.6) for placebo (HR: 0.45, 95% CI: 0.21-0.96). The median PFS was 9.7 months (95% CI: 6.6-14.0) for camrelizumab versus 6.7 months (95% CI: 4.1-8.6) for placebo (HR: 0.57, 95% CI: 0.29-1.11). Grade 3 or higher treatment-related adverse events occurred in 65.6% and 46.4% of the respective groups, mainly neutrophil count decreased and anemia.

Conclusions: Despite early termination, camrelizumab demonstrated a trend toward improved iPFS and PFS in BM of NSCLC, with an acceptable safety profile.