Radiotherapy Department, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi, China.
Radiotherapy Department, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi, China.
Int Immunopharmacol. 2021 Feb;91:107281. doi: 10.1016/j.intimp.2020.107281. Epub 2020 Dec 16.
Both pembrolizumab and lenvatinib demonstrate antitumor activity and safety in cancers. However, whether their combination is safer and more effective than monotherapies remains unknown. A systematic review was performed to assess the safety and efficacy of pembrolizumab plus lenvatinib versus their respective monotherapies in solid cancers.
PubMed, Embase, and Cochrane Library were searched. Forty-two clinical trials with 8155 patients were included.
The total ≥grade 3 adverse events (AEs) and objective response rates (ORRs) among pembrolizumab plus lenvatinib and pembrolizumab or lenvatinib monotherapies in solid cancers were 68.0% vs 17.7% vs 68.5% and 40.6% vs 20.8% vs 43.3%, respectively. The most common AEs of pembrolizumab plus lenvatinib were hypertension (20-61.1%), fatigue (12-59.1%), diarrhea (9-51.9%), hypothyroidism (25-47%), and proteinuria (8-17%). Good ORRs for combination therapy were observed in renal cell carcinoma (70%), gastric cancer (69%), melanoma (48%), head and neck squamous cell carcinoma (46%), and endometrial cancer (38-53%), while these rates were reported as 27%, 11.6-22%, 26-37%, 14.6-23%, and 11-14.3% for monotherapies, respectively. Longer median progression-free survival (mPFS) and median overall survival (mOS) were observed for hepatocellular carcinoma (mPFS 9.3 months, mOS 22.0 months), renal cell carcinoma (mPFS 19.8 months), gastric cancer (mPFS 7.1 months, mOS not reached), and endometrial cancer (mPFS 7.4 months, mOS 16.7 months).
Compared with their monotherapies, pembrolizumab plus lenvatinib showed more promising antitumor activity and resulted in higher ORRs and significant survival benefits in the above cancers. Toxicities were manageable, with no unexpected safety issues.
帕博利珠单抗和仑伐替尼在癌症中均显示出抗肿瘤活性和安全性。然而，其联合治疗是否比单药治疗更安全、更有效尚不清楚。本系统评价旨在评估在实体瘤中，帕博利珠单抗联合仑伐替尼与各自单药治疗相比的安全性和疗效。
检索了 PubMed、Embase 和 Cochrane Library。共纳入 42 项临床试验，包含 8155 例患者。
在实体瘤中，帕博利珠单抗联合仑伐替尼与帕博利珠单抗或仑伐替尼单药治疗的总≥3 级不良事件（AE）发生率和客观缓解率（ORR）分别为 68.0%比 17.7%比 68.5%和 40.6%比 20.8%比 43.3%。帕博利珠单抗联合仑伐替尼最常见的 AE 为高血压（20%-61.1%）、乏力（12%-59.1%）、腹泻（9%-51.9%）、甲状腺功能减退（25%-47%）和蛋白尿（8%-17%）。联合治疗在肾细胞癌（70%）、胃癌（69%）、黑色素瘤（48%）、头颈部鳞状细胞癌（46%）和子宫内膜癌（38%-53%）中观察到良好的 ORR，而单药治疗的这些比率分别为 27%、11.6%-22%、26%-37%、14.6%-23%和 11%-14.3%。对于肝细胞癌（mPFS 9.3 个月，mOS 22.0 个月）、肾细胞癌（mPFS 19.8 个月）、胃癌（mPFS 7.1 个月，mOS 未达到）和子宫内膜癌（mPFS 7.4 个月，mOS 16.7 个月），帕博利珠单抗联合仑伐替尼显示出更长的中位无进展生存期（mPFS）和中位总生存期（mOS）。
与单药治疗相比，帕博利珠单抗联合仑伐替尼在上述癌症中显示出更有前景的抗肿瘤活性，并且 ORR 更高，生存获益显著。毒性是可控的，没有出现意外的安全性问题。
