Dingemans Anne-Marie C, Syrigos Konstantinos, Livi Lorenzo, Paulus Astrid, Kim Sang-We, Chen Yuanbin, Felip Enriqueta, Griesinger Frank, Ohashi Kadoaki, Zalcman Gerard, Hughes Brett G M, Sørensen Jens Benn, Blais Normand, Ferreira Carlos G M, Lindsay Colin R, Dziadziuszko Rafal, Ward Patrick J, Obiozor Cynthia Chinedu, Wang Yang, Peters Solange
Erasmus MC Cancer Institute, University Medical Center, Rotterdam, the Netherlands.
Sotiria General Hospital, Athens, Greece.
Lung Cancer. 2025 Sep;207:108683. doi: 10.1016/j.lungcan.2025.108683. Epub 2025 Jul 29.
To assess the efficacy and safety of sotorasib in patients with brain metastases using data from the phase 3 CodeBreaK 200 study, which evaluated sotorasib in adults with pretreated advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC).
Patients with KRAS G12C-mutated NSCLC who progressed after platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1:1 to sotorasib or docetaxel. An exploratory post-hoc analysis evaluated central nervous system (CNS) progression-free survival (PFS) and time to CNS progression in patients with treated and stable brain metastases at baseline. Measures were assessed by blinded independent central review per study-modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Of the patients randomly assigned to receive sotorasib (n=171) or docetaxel (n=174), baseline CNS metastases were present in 40 (23%) and 29 (17%) patients, respectively. With a median follow-up of 20.0 months for this patient subgroup, median CNS PFS was longer with sotorasib compared with docetaxel (9.6 vs 4.5 months; hazard ratio, 0.43 [95% CI, 0.20-0.92]; P=0.02). Among patients with baseline treated CNS lesions of ≥10 mm, the percentage of patients who achieved CNS tumor shrinkage of ≥30% was two-fold higher with sotorasib than docetaxel (33.3% vs 15.4%). Treatment-related adverse events among patients with CNS lesions at baseline were consistent with those of the overall study population.
These results suggest intracranial activity with sotorasib complements the overall PFS benefit observed with sotorasib vs docetaxel, with safety outcomes similar to those in the general CodeBreaK 200 population.
NCT04303780.
利用3期CodeBreaK 200研究的数据，评估索托拉西布在脑转移患者中的疗效和安全性。该研究评估了索托拉西布在接受过预处理的晚期或转移性KRAS G12C突变非小细胞肺癌（NSCLC）成人患者中的疗效。
铂类化疗和检查点抑制剂治疗后病情进展的KRAS G12C突变NSCLC患者按1:1随机分组，分别接受索托拉西布或多西他赛治疗。一项探索性事后分析评估了基线时脑转移已接受治疗且病情稳定的患者的中枢神经系统（CNS）无进展生存期（PFS）和至CNS进展时间。根据研究修改后的神经肿瘤脑转移反应评估（RANO-BM）标准，由盲法独立中央审查评估各项指标。
在随机分配接受索托拉西布（n = 171）或多西他赛（n = 174）治疗的患者中，分别有40例（23%）和29例（17%）患者在基线时存在CNS转移。该患者亚组的中位随访时间为20.0个月，与多西他赛相比，索托拉西布的中位CNS PFS更长（9.6个月对4.5个月；风险比，0.43 [95% CI，0.20 - 0.92]；P = 0.02）。在基线时CNS病灶经治疗且≥10 mm的患者中，CNS肿瘤缩小≥30%的患者比例，索托拉西布组是多西他赛组的两倍（33.3%对15.4%）。基线时存在CNS病灶的患者中与治疗相关的不良事件与总体研究人群一致。
这些结果表明，索托拉西布的颅内活性补充了索托拉西布与多西他赛相比观察到的总体PFS获益，安全性结果与CodeBreaK 200总体人群相似。
NCT04303780。
