First-Line Camrelizumab Versus Placebo Plus Chemotherapy With or Without Radiotherapy for Brain Metastases in NSCLC: The CTONG 2003 Randomized Placebo-Controlled Trial.

INTRODUCTION: Retrospective studies have indicated the potential benefits of immunotherapy for brain metastases (BMs) in NSCLC. To our knowledge, 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 four to six cycles, followed by maintenance therapy with camrelizumab or placebo with or without 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 progression-free survival (PFS). The planned enrollment included 200 patients, but recruitment was terminated early because of 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% confidence interval [CI]: 7.1-25.3) for camrelizumab versus 9.9 months (95% CI: 6.3-14.6) for placebo (hazard ratio = 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 (hazard ratio = 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 decrease and anemia. CONCLUSIONS: Despite early termination, camrelizumab demonstrated a trend toward improved iPFS and PFS in the BM of NSCLC with an acceptable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04768075.