Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Cancer Center, Research Institute of Surgery, Daping Hospital, Chongqing, China.
Neuro Oncol. 2021 Jun 1;23(6):967-978. doi: 10.1093/neuonc/noaa281.
Erlotinib combined with whole-brain radiotherapy (WBRT) demonstrated a favorable objective response rate in a phase II single-arm trial of non-small cell lung cancer (NSCLC) patients with brain metastases. We assessed whether concurrent erlotinib with WBRT is safe and benefits patients in a phase III, randomized trial.
NSCLC patients with two or more brain metastases were enrolled and randomly assigned (1:1) to WBRT (n = 115) or WBRT combined with erlotinib arms (n = 109). The primary endpoint was intracranial progression-free survival (iPFS) and cognitive function (CF) was assessed by the Mini-Mental State Examination (MMSE).
A total of 224 patients from 10 centers across China were randomized to treatments. Median follow-up was 11.2 months. Median iPFS for WBRT concurrent erlotinib was 11.2 months vs 9.2 months for WBRT-alone (P = .601). Median PFS and overall survival (OS) of combination group were 5.3 vs 4.0 months (P = .825) and 12.9 vs 10.0 months (P = .545), respectively, compared with WBRT-alone. In EGFR-mutant patients, iPFS (14.6 vs 12.8 months; P = .164), PFS (8.8 vs 6.4 months; P = .702), and OS (17.5 vs 16.9 months; P = .221) were not significantly improved in combination group over WBRT-alone. Moreover, there were no significant differences in patients experiencing MMSE score change between the treatments.
Concurrent erlotinib with WBRT didn't improve iPFS and excessive CF detriment either in the intent-to-treat (ITT) population or in EGFR-mutant patients compared with WBRT-alone, suggesting that while safe for patients already taking the drug, there is no justification for adding concurrent EGFR-TKI with WBRT for the treatment of brain metastases. Trial registration: Clinical trials.gov identifier: NCT01887795.
厄洛替尼联合全脑放疗（WBRT）在一项非小细胞肺癌（NSCLC）脑转移患者的 II 期单臂试验中显示出良好的客观缓解率。我们评估了 NSCLC 伴脑转移患者中 WBRT 联合厄洛替尼的同步治疗是否安全且有益。
纳入了 2 个或更多脑转移灶的 NSCLC 患者，并按 1:1 随机分配至 WBRT 组（n=115）或 WBRT 联合厄洛替尼组（n=109）。主要终点为颅内无进展生存期（iPFS），认知功能（CF）通过简易精神状态检查（MMSE）评估。
来自中国 10 家中心的 224 例患者被随机分组。中位随访时间为 11.2 个月。WBRT 联合厄洛替尼组的中位 iPFS 为 11.2 个月，WBRT 组为 9.2 个月（P=0.601）。联合组的中位 PFS 和总生存期（OS）分别为 5.3 个月 vs 4.0 个月（P=0.825）和 12.9 个月 vs 10.0 个月（P=0.545），而 WBRT 组分别为 4.0 个月和 10.0 个月。在 EGFR 突变患者中，iPFS（14.6 个月 vs 12.8 个月；P=0.164）、PFS（8.8 个月 vs 6.4 个月；P=0.702）和 OS（17.5 个月 vs 16.9 个月；P=0.221）均无显著改善。此外，在 WBRT 联合厄洛替尼组和 WBRT 组中，MMSE 评分变化的患者之间也没有显著差异。
与 WBRT 相比，WBRT 联合厄洛替尼并未改善意向治疗（ITT）人群或 EGFR 突变患者的 iPFS 或认知功能损害，提示虽然对已服用该药的患者安全，但无理由为治疗脑转移添加 WBRT 同步 EGFR-TKI。临床试验注册：ClinicalTrials.gov 标识符：NCT01887795。
