Review
. 2020 Apr; 26(19):5062-5067.
doi: 10.1158/1078-0432.CCR-19-3979.

FDA Approval Summary: Pembrolizumab plus Lenvatinib for Endometrial Carcinoma, a Collaborative International Review under Project Orbis

Shaily Arora 1 Sanjeeve Balasubramaniam 2 Wei Zhang 2 Lijun Zhang 2 Rajeshwari Sridhara 2 Dianne Spillman 3 Jaigi P Mathai 4 Bradley Scott 4 Sarah J Golding 5 Michael Coory 5 Richard Pazdur 3 Julia A Beaver 2 
Affiliations
  • PMID: 32295834
  •     20 citations

Abstract

On September 17, 2019, FDA granted accelerated approval to pembrolizumab plus lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. The submission and review of this application was conducted through an FDA Oncology Center of Excellence initiative named Project Orbis whereby the FDA, the Australian Therapeutic Goods Administration, and Health Canada were able to simultaneously review and collaborate, rendering simultaneous approval decisions in all countries. Accelerated approval of the pembrolizumab plus lenvatinib combination was based on a single-arm trial of 94 patients, with previously treated metastatic endometrial cancer whose tumors were not MSI-H/dMMR. Efficacy was demonstrated on the basis of an objective response rate of 38.3% (95% confidence interval, 28.5%-48.9%) with 10 complete responses (10.6%) accompanied by supportive durations of response. Trials to confirm clinical benefit of this combination are ongoing. Here, we summarize the benefit-risk analysis supporting accelerated approval of the pembrolizumab plus lenvatinib combination and describe the methodology for the first Project Orbis review.

Targeting dopamine receptor D2 as a novel therapeutic strategy in endometrial cancer.
Stuart R Pierce, Ziwei Fang, +17 authors, Victoria Bae-Jump.
J Exp Clin Cancer Res, 2021 Feb 10; 40(1). PMID: 33557912    Free PMC article.
Tumor Molecular Features Predict Endometrial Cancer Patients' Survival After Open or Minimally Invasive Surgeries.
Yibo Dai, Jingyuan Wang, +2 authors, Jianliu Wang.
Front Oncol, 2021 Mar 16; 11. PMID: 33718224    Free PMC article.
Regorafenib enhances antitumor immunity via inhibition of p38 kinase/Creb1/Klf4 axis in tumor-associated macrophages.
Da-Liang Ou, Chia-Wei Chen, +6 authors, Chiun Hsu.
J Immunother Cancer, 2021 Mar 24; 9(3). PMID: 33753566    Free PMC article.
New Insights into Endometrial Cancer.
Laura Paleari, Silvia Pesce, +5 authors, Emanuela Marcenaro.
Cancers (Basel), 2021 Apr 04; 13(7). PMID: 33804979    Free PMC article.
Review.
Recent advancements of antiangiogenic combination therapies in ovarian cancer.
Daniel An, Susana Banerjee, Jung-Min Lee.
Cancer Treat Rev, 2021 May 30; 98. PMID: 34051628    Free PMC article.
Review.
FDA Approval Summary: Nivolumab with Ipilimumab and Chemotherapy for Metastatic Non-small Cell Lung Cancer, A Collaborative Project Orbis Review.
Paz J Vellanki, Flora Mulkey, +16 authors, Harpreet Singh.
Clin Cancer Res, 2021 Feb 27; 27(13). PMID: 33632925    Free PMC article.
Endometrial cancer from early to advanced-stage disease: an update for radiologists.
Cibele Luna, Patricia Balcacer, +2 authors, Francesco Alessandrino.
Abdom Radiol (NY), 2021 Jul 24; 46(11). PMID: 34297164
Review.
Systematic review of combinations of targeted or immunotherapy in advanced solid tumors.
Aaron C Tan, Stephen J Bagley, +18 authors, Mustafa Khasraw.
J Immunother Cancer, 2021 Jul 04; 9(7). PMID: 34215688    Free PMC article.
Systematic Review.
Two Dimensional-Difference in Gel Electrophoresis (2D-DIGE) Proteomic Approach for the Identification of Biomarkers in Endometrial Cancer Serum.
Blendi Ura, Stefania Biffi, +13 authors, Giuseppe Ricci.
Cancers (Basel), 2021 Jul 25; 13(14). PMID: 34298850    Free PMC article.
Endometrial Cancer Molecular Characterization: The Key to Identifying High-Risk Patients and Defining Guidelines for Clinical Decision-Making?
Regina Esi Mensimah Baiden-Amissah, Daniela Annibali, Sandra Tuyaerts, Frederic Amant.
Cancers (Basel), 2021 Aug 28; 13(16). PMID: 34439142    Free PMC article.
Review.
Doxorubicin plus lurbinectedin in patients with advanced endometrial cancer: results from an expanded phase I study.
Rebecca Kristeleit, Victor Moreno, +10 authors, Martin Forster.
Int J Gynecol Cancer, 2021 Oct 07; 31(11). PMID: 34610971    Free PMC article.
TCF3 is epigenetically silenced by EZH2 and DNMT3B and functions as a tumor suppressor in endometrial cancer.
Tao Gui, Ming Liu, +17 authors, Quan Zhao.
Cell Death Differ, 2021 Jun 28; 28(12). PMID: 34175897    Free PMC article.
PARP inhibitors and immunotherapy in ovarian and endometrial cancers.
Rowan E Miller, Amy J Lewis, Melanie E Powell.
Br J Radiol, 2021 Apr 22; 94(1128). PMID: 33882241    Free PMC article.
Review.
Identifying immune subtypes of uterine corpus endometrial carcinoma and a four-paired-lncRNA signature with immune-related lncRNAs.
Nan Li, Kai Yu, Zhong Lin, Dingyuan Zeng.
Exp Biol Med (Maywood), 2021 Oct 28; 247(3). PMID: 34704492    Free PMC article.
Endometrial Cancer: Transitioning from Histology to Genomics.
Cristina Mitric, Marcus Q Bernardini.
Curr Oncol, 2022 Feb 25; 29(2). PMID: 35200562    Free PMC article.
Review.
Sevoflurane Suppresses the Growth, Metastasis, and Invasion of Endometrial Carcinoma Cells via miR-195-5p/JAK2 Axis.
Guowei Fu, Junlan Huang, Zhouquan Wu, Lin Zhao.
Comput Math Methods Med, 2022 Mar 05; 2022. PMID: 35242202    Free PMC article.
Lenvatinib Plus Camrelizumab vs. Lenvatinib Monotherapy as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Cohort Study.
Qi Li, Mengran Cao, +9 authors, Jinzhang Chen.
Front Oncol, 2022 Mar 15; 12. PMID: 35280760    Free PMC article.
U.S. FDA Drug Approvals for Gynecological Malignancies: A Decade in Review.
Shaily Arora, Preeti Narayan, +20 authors, Julia A Beaver.
Clin Cancer Res, 2021 Oct 30; 28(6). PMID: 34711631    Free PMC article.
Review.
Lenvatinib Beyond First-Line Therapy in Patients With Advanced Biliary Tract Carcinoma.
Yunchao Wang, Xiaobo Yang, +9 authors, Haitao Zhao.
Front Oncol, 2022 Mar 22; 12. PMID: 35311147    Free PMC article.
The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development.
Zacharias Fasoulakis, Antonios Koutras, +14 authors, Emmanuel N Kontomanolis.
Cancers (Basel), 2022 Apr 13; 14(7). PMID: 35406423    Free PMC article.
Review.