纳武利尤单抗治疗既往治疗的晚期非小细胞肺癌患者的 4 年生存：汇总分析。
Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis.
机构信息
H Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Fox Chase Cancer Center, Philadelphia, PA, USA.
出版信息
Lancet Oncol. 2019 Oct;20(10):1395-1408. doi: 10.1016/S1470-2045(19)30407-3. Epub 2019 Aug 14.
BACKGROUND
Phase 3 clinical data has shown higher proportions of patients with objective response, longer response duration, and longer overall survival with nivolumab versus docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival.
METHODS
We pooled data from four clinical studies of nivolumab in patients with previously treated NSCLC (CheckMate 017, 057, 063, and 003) to evaluate survival outcomes. Trials of nivolumab in the second-line or later setting with at least 4 years follow-up were included. Comparisons of nivolumab versus docetaxel included all randomised patients from the phase 3 CheckMate 017 and 057 studies. We did landmark analyses by response status at 6 months to determine post-landmark survival outcomes. We excluded patients who did not have a radiographic tumour assessment at 6 months. Safety analyses included all patients who received at least one dose of nivolumab.
FINDINGS
Across all four studies, 4-year overall survival with nivolumab was 14% (95% CI 11-17) for all patients (n=664), 19% (15-24) for those with at least 1% PD-L1 expression, and 11% (7-16) for those with less than 1% PD-L1 expression. In CheckMate 017 and 057, 4-year overall survival was 14% (95% CI 11-18) in patients treated with nivolumab, compared with 5% (3-7) in patients treated with docetaxel. Survival subsequent to response at 6 months on nivolumab or docetaxel was longer than after progressive disease at 6 months, with hazard ratios for overall survival of 0·18 (95% 0·12-0·27) for nivolumab and 0·43 (0·29-0·65) for docetaxel; for stable disease versus progressive disease, hazard ratios were 0·52 (0·37-0·71) for nivolumab and 0·80 (0·61-1·04) for docetaxel. Long-term data did not show any new safety signals.
INTERPRETATION
Patients with advanced NSCLC treated with nivolumab achieved a greater duration of response compared with patients treated with docetaxel, which was associated with a long-term survival advantage.
FUNDING
Bristol-Myers Squibb.
背景
在先前治疗的晚期非小细胞肺癌（NSCLC）患者中，与多西他赛相比，nivolumab 具有更高的客观缓解率、更长的缓解持续时间和更长的总生存期。我们旨在评估 nivolumab 的长期获益，以及反应和疾病控制对后续生存的影响。
方法
我们汇总了 nivolumab 在先前治疗的 NSCLC 患者中四项临床研究的数据（CheckMate 017、057、063 和 003），以评估生存结局。纳入了在二线及以上治疗中至少有 4 年随访的 nivolumab 临床试验。nivolumab 与多西他赛的比较包括了 phase 3 CheckMate 017 和 057 研究中的所有随机患者。我们根据 6 个月时的反应状态进行了 landmark 分析，以确定 landmark 后生存结局。我们排除了在 6 个月时没有进行影像学肿瘤评估的患者。安全性分析包括了至少接受过一次 nivolumab 治疗的所有患者。
结果
在所有四项研究中，所有患者（n=664）的 nivolumab 4 年总生存率为 14%（95%CI 11-17），至少有 1% PD-L1 表达的患者为 19%（15-24），而 PD-L1 表达低于 1%的患者为 11%（7-16）。在 CheckMate 017 和 057 中，与多西他赛相比，接受 nivolumab 治疗的患者的 4 年总生存率为 14%（95%CI 11-18），而接受多西他赛治疗的患者为 5%（3-7）。nivolumab 或多西他赛治疗 6 个月后有反应的患者的生存时间长于 6 个月时疾病进展的患者，总生存的风险比为 nivolumab 0·18（95%CI 0·12-0·27），多西他赛 0·43（0·29-0·65）；而 nivolumab 的稳定疾病与疾病进展的风险比为 0·52（0·37-0·71），多西他赛为 0·80（0·61-1·04）。长期数据未显示任何新的安全性信号。
解释
与接受多西他赛治疗的患者相比，接受 nivolumab 治疗的晚期 NSCLC 患者的缓解持续时间更长，这与长期生存获益相关。
资助
百时美施贵宝公司。
Zotero 插件