Department of Medical Oncology, Yonsei Cancer Center, Yonsei Song-Dang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, Korea.
Department of Medical Oncology, Cote d'Azur University, Centre Antoine Lacassagne, Nice, France.
Cancer. 2024 Oct 1;130(19):3278-3288. doi: 10.1002/cncr.35387. Epub 2024 Jun 21.
Novel treatments are needed for patients with advanced, triple-negative breast cancer (TNBC) that progresses or recurs after first-line treatment with chemotherapy. The authors report results from the TNBC cohort of the multicohort, open-label, single-arm, phase 2 LEAP-005 study of lenvatinib plus pembrolizumab in patients with advanced solid tumors (ClinicalTrials.gov identifier NCT03797326).
Eligible patients had metastatic or unresectable TNBC with disease progression after one or two lines of therapy. Patients received lenvatinib (20 mg daily) plus pembrolizumab (200 mg every 3 weeks; up to 35 cycles). The primary end points were the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1, and safety (adverse events graded by the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0). Duration of response, progression-free survival, and overall survival were secondary end points.
Thirty-one patients were enrolled. The objective response rate by investigator assessment was 23% (95% confidence interval [CI], 10%-41%). Overall, the objective response rate by blinded independent central review (BICR) was 32% (95% CI, 17%-51%); and, in patients who had programmed cell death ligand 1 combined positive scores ≥10 (n = 8) and <10 (n = 22), the objective response rate was 50% (95% CI, 16%-84%) and 27% (95% CI, 11%-50%), respectively. The median duration of response by BICR was 12.1 months (range, from 3.0+ to 37.9+ months). The median progression-free survival by BICR was 5.1 months (95% CI, 1.9-11.8 months) and the median overall survival was 11.4 months (95% CI, 4.1-21.7 months). Treatment-related adverse events occurred in 94% of patients (grade 3, 52%; grade 4, 0%). One patient died due to a treatment-related adverse event of subarachnoid hemorrhage.
The combination of lenvatinib plus pembrolizumab demonstrated antitumor activity with a manageable safety profile in patients with previously treated, advanced TNBC.
需要为接受一线化疗后进展或复发的晚期三阴性乳腺癌（TNBC）患者寻找新的治疗方法。作者报告了多队列、开放标签、单臂、II 期 LEAP-005 研究中仑伐替尼联合帕博利珠单抗治疗晚期实体瘤患者的 TNBC 队列结果（ClinicalTrials.gov 标识符：NCT03797326）。
符合条件的患者为转移性或不可切除的 TNBC，且在一线治疗后发生疾病进展。患者接受仑伐替尼（20mg 每日）联合帕博利珠单抗（200mg 每 3 周；最多 35 个周期）治疗。主要终点为根据实体瘤反应评价标准 1.1 版评估的客观缓解率和安全性（不良事件按美国国立癌症研究所不良事件通用术语标准 4.0 分级）。缓解持续时间、无进展生存期和总生存期为次要终点。
共纳入 31 例患者。研究者评估的客观缓解率为 23%（95%置信区间[CI]：10%-41%）。总体而言，盲法独立中心评价（BICR）的客观缓解率为 32%（95%CI：17%-51%）；且在程序性死亡配体 1 联合阳性评分≥10（n=8）和<10（n=22）的患者中，客观缓解率分别为 50%（95%CI：16%-84%）和 27%（95%CI：11%-50%）。BICR 评估的缓解持续时间中位数为 12.1 个月（范围：3.0+至 37.9+个月）。BICR 评估的无进展生存期中位数为 5.1 个月（95%CI：1.9-11.8 个月），总生存期中位数为 11.4 个月（95%CI：4.1-21.7 个月）。94%的患者发生治疗相关不良事件（3 级，52%；4 级，0%）。1 例患者因蛛网膜下腔出血的治疗相关不良事件死亡。
仑伐替尼联合帕博利珠单抗在先前接受过治疗的晚期 TNBC 患者中显示出抗肿瘤活性，安全性可管理。
