美国纪念斯隆·凯特琳癌症中心Robert Motzer联合丹娜-法伯癌症研究所Toni K. Choueiri团队，研究了乐伐替尼联合派姆单抗或依维莫司治疗晚期肾细胞癌的效果。2021年4月8日，该研究发表在《新英格兰医学杂志》上。

乐伐替尼联合派姆单抗或依维莫司对晚期肾细胞癌有抑制作用。与舒尼替尼相比，这些方案的疗效尚不清楚。

在这项临床3期试验中，研究组共招募了1069名既往未接受过全身治疗的晚期肾细胞癌患者，将其按1：1：1随机分配，其中355名接受乐伐替尼+派姆单抗治疗，357名接受乐伐替尼+依维莫司治疗，357名接受舒尼替尼治疗。主要终点是无进展生存率。研究组还评估了总体生存率和安全性。

乐伐替尼+派姆单抗组的中位无进展生存期为23.9个月，乐伐替尼+依维莫司组为14.7个月，均显著长于舒尼替尼组（9.2个月）。乐伐替尼+派姆单抗组的总生存期显著长于舒尼替尼组，但乐伐替尼+依维莫司组与舒尼替尼组无显著差异。乐伐替尼+派姆单抗组中有82.4%的患者在治疗期间出现3级及以上不良事件或恶化，乐伐替尼+依维莫司组中有83.1%，舒尼替尼组中有71.8%。任何一组中至少有10%的患者发生3级或以上不良事件包括高血压、腹泻和脂肪酶水平升高。

研究结果表明，乐伐替尼联合派姆单抗治疗晚期肾细胞癌患者，与舒尼替尼相比，无进展生存期和总生存期显著延长。

附：英文原文

Title: Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma

Author: Robert Motzer, M.D.,, Boris Alekseev, M.D.,, Sun-Young Rha, M.D.,, Camillo Porta, M.D.,, Masatoshi Eto, M.D.,, Thomas Powles, M.D.,, Viktor Grünwald, M.D.,, Thomas E. Hutson, M.D.,, Evgeny Kopyltsov, M.D.,, María J. Méndez-Vidal, M.D.,, Vadim Kozlov, M.D.,, Anna Alyasova, M.D.,, Sung-Hoo Hong, M.D.,, Anil Kapoor, M.D.,, Teresa Alonso Gordoa, M.D.,, Jaime R. Merchan, M.D.,, Eric Winquist, M.D.,, Pablo Maroto, M.D.,, Jeffrey C. Goh, M.D.,, Miso Kim, M.D.,, Howard Gurney, M.B., B.S.,, Vijay Patel, M.D.,, Avivit Peer, M.D.,, Giuseppe Procopio, M.D.,, Toshio Takagi, M.D.,, Bohuslav Melichar, M.D.,, Frederic Rolland, M.D.,, Ugo De Giorgi, M.D.,, Shirley Wong, M.D.,, Jens Bedke, M.D.,, Manuela Schmidinger, M.D.,, Corina E. Dutcus, M.D.,, Alan D. Smith, M.D.,, Lea Dutta, M.D.,, Kalgi Mody, M.D.,, Rodolfo F. Perini, M.D.,, Dongyuan Xing, Ph.D.,, and Toni K. Choueiri, M.D.

Issue&Volume: 2021-02-13

Abstract:

Background

Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.

Methods

In this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated.

Results

A total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P<0.001) and was longer with lenvatinib plus everolimus than with sunitinib (median, 14.7 vs. 9.2 months; hazard ratio, 0.65; 95% CI, 0.53 to 0.80; P<0.001). Overall survival was longer with lenvatinib plus pembrolizumab than with sunitinib (hazard ratio for death, 0.66; 95% CI, 0.49 to 0.88; P=0.005) but was not longer with lenvatinib plus everolimus than with sunitinib (hazard ratio, 1.15; 95% CI, 0.88 to 1.50; P=0.30). Grade 3 or higher adverse events emerged or worsened during treatment in 82.4% of the patients who received lenvatinib plus pembrolizumab, 83.1% of those who received lenvatinib plus everolimus, and 71.8% of those who received sunitinib. Grade 3 or higher adverse events occurring in at least 10% of the patients in any group included hypertension, diarrhea, and elevated lipase levels.

Conclusions

Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib.

DOI: 10.1056/NEJMoa2035716

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2035716