Voss Martin H, Gurney Howard, Atduev Vagif, Suarez Cristina, Climent Miguel A, Pook David, Tomczak Piotr, Barthélémy Philippe, Lee Jae Lyun, Nalbandian Taron, Stus Viktor, Ferguson Thomas, Wiechno Pawel, Gokmen Erhan, Lacombe Louis, Gedye Craig, Cornell Jerry, Sharma Manish, Burgents Joseph E, Albiges Laurence
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Macquarie University, Sydney, Australia.
Eur Urol. 2025 Jul 23. doi: 10.1016/j.eururo.2025.05.019.
Initial results from the KEYNOTE-B61 trial demonstrated that pembrolizumab combined with lenvatinib has promising antitumor activity in previously untreated advanced non-clear-cell renal cell carcinoma (nccRCC). We report updated efficacy and safety results after nearly 2 yr of follow-up.
The single-arm, multicenter, phase 2 KEYNOTE-B61 trial enrolled patients aged ≥18 yr with previously untreated advanced nccRCC. All participants received pembrolizumab 400 mg intravenously every 6 wk (up to 18 cycles, approx. 2 yr) plus lenvatinib 20 mg orally once daily. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1 as assessed on blinded independent central review. Duration of response (DOR) and safety were secondary endpoints.
A total of 158 patients received at least one dose of study treatment. Median follow-up was 22.8 mo (range 16.6-27.6). The ORR was 51% (95% confidence interval 43-59); 13 patients (8.2%) had a confirmed complete response and 67 (42%) had a confirmed partial response. In the subgroup with a confirmed response, median DOR was 19.5 mo (range 1.5+ to 23.5+). ORR was generally consistent across subgroups, including histologic subtypes (34-67%) and the presence of sarcomatoid features (47%). Grade 3 or 4 treatment-related adverse events were reported for 92 patients (58%). No deaths due to treatment-related adverse events occurred.
After approximately 2 yr of follow-up, pembrolizumab plus lenvatinib showed durable antitumor activity in KEYNOTE-B61, with no new safety signals. These results support pembrolizumab + lenvatinib as a first-line treatment option for advanced nccRCC.
KEYNOTE-B61试验的初步结果表明，帕博利珠单抗联合乐伐替尼在既往未接受过治疗的晚期非透明细胞肾细胞癌（nccRCC）中具有良好的抗肿瘤活性。我们报告了近2年随访后的疗效和安全性更新结果。
单臂、多中心2期KEYNOTE-B61试验纳入了年龄≥18岁、既往未接受过治疗的晚期nccRCC患者。所有参与者每6周静脉注射400 mg帕博利珠单抗（最多18个周期，约2年），并每天口服一次20 mg乐伐替尼。主要终点是根据实体瘤疗效评价标准v1.1在盲法独立中央审查中评估的客观缓解率（ORR）。缓解持续时间（DOR）和安全性为次要终点。
共有158例患者接受了至少一剂研究治疗。中位随访时间为22.8个月（范围16.6 - 27.6个月）。ORR为51%（95%置信区间43 - 59）；13例患者（8.2%）获得确认的完全缓解，67例（42%）获得确认的部分缓解。在获得确认缓解的亚组中，中位DOR为19.5个月（范围1.5 +至23.5 +）。ORR在各亚组中总体一致，包括组织学亚型（34 - 67%）和肉瘤样特征的存在情况（47%）。92例患者（58%）报告了3级或4级治疗相关不良事件。未发生因治疗相关不良事件导致的死亡。
经过约2年的随访，帕博利珠单抗联合乐伐替尼在KEYNOTE-B61试验中显示出持久的抗肿瘤活性，且无新的安全信号。这些结果支持帕博利珠单抗 + 乐伐替尼作为晚期nccRCC的一线治疗选择。
