KEYNOTE-158 期研究中帕博利珠单抗单药治疗晚期甲状腺癌患者的疗效和安全性。
Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study.
机构信息
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
出版信息
Cancer. 2023 Apr 15;129(8):1195-1204. doi: 10.1002/cncr.34657. Epub 2023 Feb 7.
BACKGROUND
The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers.
METHODS
Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review.
RESULTS
A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9-54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%-13.5%), and median duration of response was 18.4 (range, 4.2-47.2+) months. ORR was 8.7% (95% CI, 2.4%-20.8%) among patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 (n = 46) and 5.7% (95% CI, 1.2%-15.7%) among patients with PD-L1 CPS <1 (n = 53). Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9-6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grade 3-5, 14.6%).
CONCLUSIONS
Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These results provide evidence of modest antitumor activity in this setting regardless of tumor PD-L1 expression. Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker-driven patient selection or combination of immune checkpoint inhibitors with other agents, in order to achieve higher response rates than observed in this study.
背景
作者报告了多队列 2 期 KEYNOTE-158 研究（NCT02628067）甲状腺癌队列的结果，该研究评估了 pembrolizumab 单药治疗既往治疗过的癌症患者。
方法
符合条件的患者有组织学和/或细胞学证实的甲状腺乳头状或滤泡状癌，先前治疗失败或不耐受，且根据实体瘤反应评估标准（RECIST）v1.1 有可测量的疾病。患者每 3 周接受 pembrolizumab（200mg）治疗，最多 35 个周期。主要终点是独立中心评估的 RECIST v1.1 客观缓解率（ORR）。
结果
共纳入 103 例患者接受 pembrolizumab 治疗。从首次剂量到数据截止日期（2020 年 10 月 5 日）的中位时间为 49.4（范围，43.9-54.9）个月。ORR 为 6.8%（95%置信区间[CI]，2.8%-13.5%），中位缓解持续时间为 18.4（范围，4.2-47.2+）个月。在程序性死亡配体 1（PD-L1）联合阳性评分（CPS）≥1 的患者（n=46）中，ORR 为 8.7%（95%CI，2.4%-20.8%），而在 PD-L1 CPS<1 的患者（n=53）中，ORR 为 5.7%（95%CI，1.2%-15.7%）。中位总生存期和无进展生存期分别为 34.5（95%CI，21.2-未达到）和 4.2（95%CI，3.9-6.2）个月。69.9%的患者发生治疗相关不良事件（3-5 级，14.6%）。
结论
pembrolizumab 在一小部分晚期甲状腺癌患者中显示出可管理的毒性和持久的抗肿瘤活性。这些结果表明，无论肿瘤 PD-L1 表达如何，在这种情况下都有适度的抗肿瘤活性。未来评估免疫检查点抑制剂在分化型甲状腺癌患者中的研究应侧重于基于生物标志物的患者选择，或免疫检查点抑制剂与其他药物联合使用，以达到高于本研究观察到的反应率。
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