In a Chinese phase II study (C-Brain) reported in The Lancet Oncology, Xu et al found that brain radiotherapy in combination with camrelizumab and platinum-doublet chemotherapy produced “promising” results in patients with previously untreated advanced non–small cell lung cancer (NSCLC) with brain metastases.
Study Details
Sixty-five patients with no actionable driver mutations (EGFR, ALK, or ROS1) were enrolled in the multicenter trial between May 2020 and January 2023. Patients received stereotactic radiosurgery in 9–22 Gy per fraction for one to three fractions to a total dose of 22–27 Gy; whole-brain radiotherapy was delivered in 3 Gy per fraction 5 days per week to a total of 30 Gy. Patients then received camrelizumab at 200 mg every 3 weeks and investigator-selected platinum-doublet chemotherapy (pemetrexed at 500 mg/m² plus carboplatin area under the curve = 5 or cisplatin at 75 mg/m²) for nonsquamous NSCLC (n = 50), and nab-paclitaxel at 260 mg/m² plus carboplatin or cisplatin for squamous NSCLC (n = 15) for four to six cycles. Patients with disease control received maintenance with camrelizumab alone for squamous NSCLC or camrelizumab/pemetrexed every 3 weeks for nonsquamous NSCLC. The primary outcome measure was 6-month progression-free survival.
Key Findings
Median follow-up was 14.1 months (interquartile range = 9.0–20.3 months) at data cutoff in December 2023. Progression-free survival at 6 months was 71.7% (95% confidence interval [CI] = 58.9%–81.1%).
Median progression-free survival was 10.7 months (95% CI = 7.5–15.7 months), with 12- and 24-month rates of 44.2% and 26.8%, respectively. Median intracranial progression-free survival was 16.1 months (95% CI = 13.0 months to not reached), with 12- and 24-month rates of 65.6% and 44.7%, respectively. Median overall survival was 20.9 months (95% CI = 13.8–27.7 months).
Grade 3 or 4 treatment-related adverse events occurred in 55% of patients, most commonly decreased neutrophils (22%), decreased white blood cells (15%), decreased platelets (15%), and decreased lymphocytes (14%). Radiation necrosis (all grade 1 or 2) occurred in three patients (5%). Serious treatment-related adverse events occurred in 8% of patients. Discontinuation of any study drug due to treatment-related adverse events occurred in 17%. No treatment-related deaths were reported.
The investigators concluded, “Brain radiotherapy combined with camrelizumab and platinum-doublet chemotherapy shows promising efficacy and manageable toxicity and could be a potential treatment option for patients with brain metastases from NSCLC. Randomized controlled trials will be required to confirm these findings.”
Yun Fan, MD, of Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Beijing Xisike Clinical Oncology Research Foundation and Jiangsu Hengrui Pharmaceuticals. For full disclosures of the study authors, visit thelancet.com.
