Dana-Farber/Harvard Cancer Center, Boston, Massachusetts.
Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Cancer. 2019 Sep 15;125(18):3208-3218. doi: 10.1002/cncr.32190. Epub 2019 Jun 27.
Response patterns with immune checkpoint inhibitors may be different from those with chemotherapy. Therefore, assessment of response to immunotherapy with the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, could result in premature treatment termination. The randomized, open-label, phase 3 CheckMate 141 trial (NCT02105636), which evaluated nivolumab in recurrent/metastatic squamous cell carcinoma of the head and neck after platinum therapy, allowed treatment beyond first RECIST-defined progression (TBP) according to protocol-specified criteria.
In CheckMate 141, patients with RECIST-defined progression who had a stable performance status and demonstrated clinical benefit without rapid disease progression were permitted to receive TBP with nivolumab at 3 mg/kg every 2 weeks until further progression, which was defined as an additional ≥10% increase in tumor volume. This post hoc analysis evaluated outcomes for patients who received TBP with nivolumab.
Of 240 patients randomized to nivolumab, 146 experienced RECIST-defined progression. Sixty-two of these patients received TBP, and 84 discontinued treatment (no TBP). Among the 60 TBP patients evaluable for response, 15 (25%) had no change in their tumor burden, and 15 (25%) had reductions in target lesion size; 3 patients (5%) had reductions >30%. The median overall survival among TBP patients was 12.7 months (95% confidence interval, 9.7-14.6 months). No new safety signals were observed with TBP. Exploratory analyses of immune cell biomarkers suggested a potential relationship with initial and TBP responses.
Tumor burden reduction was noted in a proportion of patients who received TBP with nivolumab in CheckMate 141. Additional research is warranted to identify factors predictive of a TBP benefit in this population.
免疫检查点抑制剂的应答模式可能与化疗不同。因此，根据实体瘤反应评价标准（RECIST）1.1 评价免疫治疗的应答可能导致过早终止治疗。这项随机、开放标签、3 期 CheckMate 141 试验（NCT02105636）评估了纳武利尤单抗在铂类治疗后的复发/转移性头颈部鳞状细胞癌中的作用，根据方案规定的标准，允许在首次 RECIST 定义的进展（TBP）后进行治疗。
在 CheckMate 141 中，RECIST 定义的进展患者如果具有稳定的表现状态，并且在没有快速疾病进展的情况下表现出临床获益，则允许接受纳武利尤单抗 TBP，剂量为 3 mg/kg，每 2 周一次，直到进一步进展，这被定义为肿瘤体积增加≥10%。这项事后分析评估了接受纳武利尤单抗 TBP 的患者的结局。
在随机分配到纳武利尤单抗的 240 例患者中，有 146 例出现 RECIST 定义的进展。其中 62 例患者接受了 TBP，84 例患者停止了治疗（未接受 TBP）。在 60 例可评估 TBP 应答的 TBP 患者中，15 例（25%）肿瘤负荷无变化，15 例（25%）靶病灶缩小；3 例（5%）肿瘤缩小>30%。TBP 患者的中位总生存期为 12.7 个月（95%置信区间，9.7-14.6 个月）。TBP 未观察到新的安全性信号。免疫细胞生物标志物的探索性分析表明，与初始和 TBP 应答之间存在潜在的关系。
在 CheckMate 141 中，接受纳武利尤单抗 TBP 的患者中，有一部分患者的肿瘤负荷降低。需要进一步的研究来确定该人群中 TBP 获益的预测因素。
