A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier cancer research network LUN 14-179
A phase 2 trial of consolidation pembrolizumab following concurrent chemoradiation for patients with unresectable stage III non-small cell lung cancer: Hoosier cancer research network LUN 14-179
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DOI：
10.1002/cncr.33083
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发表时间：
2020-07-22
期刊：
影响因子：
6.2
通讯作者：
Hanna, Nasser H.
中科院分区：
文献类型：
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作者：
Durm, Greg A.;Jabbour, Salma K.;Hanna, Nasser H.
背景不可切除的III期非小细胞肺癌（NSCLC）患者的五年总生存期（OS）很差。直到最近，标准的治疗是单独的同步放化疗。转移性非小细胞肺癌患者抗程序性死亡1抗体治疗已证明改善OS。本试验评估了pembrolizumab作为巩固治疗后，同时放化疗的患者不可切除的III期疾病。方法对不能手术切除的Ⅲ期非小细胞肺癌（NSCLC）患者采用顺铂联合足叶乙甙、顺铂联合培美曲塞或卡铂联合紫杉醇同步放化疗，放疗剂量59.4 ~ 66.6戈伊。入组未进展的患者，并接受帕博利珠单抗（200 mg静脉注射，每3周一次，持续12个月）。主要终点是至转移性疾病或死亡的时间（TMDD）。次要终点包括无进展生存期（PFS）和OS。结果93例患者（92例疗效）的中位随访时间为32.2个月（范围，1.2-46.6个月）。中位TMDD为30.7个月（95%置信区间[CI]，18.7个月至未达到），显著长于历史对照12个月（P < .0001）。中位PFS为18.7个月（95% CI，12.4-33.8个月），中位OS为35.8个月（95% CI，24.2个月至未达到）。1年、2年和3年OS估计值分别为81.2%、62.0%和48.5%。40例患者（43.5%）完成了12个月的治疗（中位周期数，13.5）。在16例患者（17.2%）中观察到症状性肺炎（2级或以上）;这些病例包括4例3级事件（4.3%）、1例4级事件（1.1%）和1例5级事件（1.1%）。结论：与单纯放化疗的历史对照相比，同步放化疗后巩固派姆单抗可改善TMDD、PFS和OS。3 - 5级肺炎的发生率与单纯放化疗的发生率相似。
Background Five-year overall survival (OS) for patients with unresectable stage III non-small cell lung cancer (NSCLC) is poor. Until recently, a standard of care was concurrent chemoradiation alone. Patients with metastatic NSCLC treated with anti-programmed death 1 antibodies have demonstrated improved OS. This trial evaluated pembrolizumab as consolidation therapy after concurrent chemoradiation in patients with unresectable stage III disease. Methods Patients with unresectable stage III NSCLC received concurrent chemoradiation with cisplatin and etoposide, cisplatin and pemetrexed, or carboplatin and paclitaxel and 59.4 to 66.6 Gy of radiation. Patients with nonprogression of disease were enrolled and received pembrolizumab (200 mg intravenously every 3 weeks for up to 12 months). The primary endpoint was the time to metastatic disease or death (TMDD). Secondary endpoints included progression-free survival (PFS) and OS. Results The median follow-up for 93 patients (92 for efficacy) was 32.2 months (range, 1.2-46.6 months). The median TMDD was 30.7 months (95% confidence interval [CI], 18.7 months to not reached), which was significantly longer than the historical control of 12 months (P < .0001). The median PFS was 18.7 months (95% CI, 12.4-33.8 months), and the median OS was 35.8 months (95% CI, 24.2 months to not reached). The 1-, 2-, and 3-year OS estimates were 81.2%, 62.0%, and 48.5%, respectively. Forty patients (43.5%) completed 12 months of treatment (median number of cycles, 13.5). Symptomatic pneumonitis (grade 2 or higher) was noted in 16 patients (17.2%); these cases included 4 grade 3 events (4.3%), 1 grade 4 event (1.1%), and 1 grade 5 event (1.1%). Conclusions Consolidation pembrolizumab after concurrent chemoradiation improves TMDD, PFS, and OS in comparison with historical controls of chemoradiation alone. Rates of grade 3 to 5 pneumonitis were similar to those reported with chemoradiation alone.