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Review
. 2022 Dec;167(3):540-546.
doi: 10.1016/j.ygyno.2022.10.012. Epub 2022 Oct 22.

Looking beyond carboplatin and paclitaxel for the treatment of advanced/recurrent endometrial cancer

Maria Rubinstein  1 , Sherry Shen  2 , Bradley J Monk  3 , David S P Tan  4 , Angélica Nogueira-Rodrigues  5 , Daisuke Aoki  6 , Jalid Sehouli  7 , Vicky Makker  8
Affiliations
Review

Looking beyond carboplatin and paclitaxel for the treatment of advanced/recurrent endometrial cancer

Maria Rubinstein et al. Gynecol Oncol. 2022 Dec.

Abstract

Endometrial cancer incidence and mortality are rising among all ethnic groups. Carboplatin plus paclitaxel is the established frontline treatment for advanced/recurrent disease; however, subsequent treatment with traditional cytotoxic chemotherapy is challenging. The molecular characterization of endometrial cancer has provided important insights into the biological drivers of carcinogenesis, which has allowed for the development of newer precision immunotherapies and targeted therapies, including pembrolizumab, dostarlimab, and lenvatinib. Until recently, platinum rechallenge was often considered at the time of recurrence, given the lack of other available therapeutic options; however, "platinum sensitivity" in endometrial cancer is subjective and largely based on expert opinion and/or practitioner experience. Small retrospective studies have tried to provide guidance on the utility of platinum rechallenge, but they are limited by variable patient characteristics and small sample sizes. The applicability of these retrospective studies to contemporary clinical practice is difficult in the setting of changing patient demographics, a better understanding of endometrial cancer drivers, and the recent approvals of immune checkpoint inhibitors and the combination of lenvatinib plus pembrolizumab in the second-line setting. The primary focus of this review is to distill the available data regarding platinum-doublet chemotherapy rechallenge and highlight recent pivotal developments in endometrial cancer treatment, as well as future directions.

Keywords: Carboplatin; Chemotherapy; Endometrial cancer; Paclitaxel; Platinum sensitivity; Treatment.

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Conflict of interest statement

Conflict of interest statement Outside the submitted work, M Rubinstein reports funding from Merck, Zentalis, and AstraZeneca. V Makker reports advisory board participation for Eisai, Merck, Clovis, Faeth, Duality, Morphyes, Karyopharm, Novartis, Lilly, and Immunocore. A Nogueira-Rodrigues is a speaker for AstraZeneca, Merck, Roche, Daiichi Sankyo, Pfizer, Oncologia Brasil, and GSK; and is a consultant for Agenus, AstraZeneca, Eisai, Merck, Roche, and GSK. D Aoki reports consulting fees from Abbie, MSD, AstraZeneca, Takeda, Eisai, and Chugai; and personal fees from MSD, AstraZeneca, Eisai, Genmab, Takeda, Chugai, and Myriad Genetics. S Shen reports payment/honoraria from MJH Life Sciences. J Sehouli reports funding from GSK, Clovis, AstraZeneca, Tesaro, MSD, and Merck; consulting fees from GSK, Clovis, AstraZeneca, Tesaro, MSD, Merck, Roche, Pharmamar, and Eisai; payment/honoraria and advisory board from GSK, Clovis, AstraZeneca, Tesaro, MSD, Merck, Pharmamar, Novocure, and Incyte; payment from GSK, Clovis, AstraZeneca, Tesaro, MSD, Merck, Pharmamar, Novocure, and Eisai; support for meetings/travel from AstraZeneca, Roche, GSK, Tesaro, and Pharmamar; and leadership/fiduciary role for NOGGO, AGO, ENGAGE, and ESGO. DSP Tan reports consultancy fees and honoraria from AstraZeneca, Roche, MSD, Merck Serono, Bayer, Eisai, GSK, Boehringer Ingelheim; institutional research funding from AstraZeneca, Bayer, MSD, Eisai, BMS, Roche and Karyopharm; stock ownership of the Asian Microbiome Library (AMiLi); and support from the Singapore Ministry of Health's National Medical Research Council Clinician Scientist Award and Pangestu Family Foundation Gynaecological Cancer Research Fund. BJ Monk reports consulting fees from Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Easai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, TESARO/GSK, US Oncology Research, VBL, Verastem, and Zentalis; and payment/honoraria from AstraZeneca, Clovis, Easai, Merck, Myriad, Roche/Genentech, and TESARO/GSK.

Figures

Figure 1:
Figure 1:. Timeline of Approvals for Second-Line Treatment of Endometrial Cancer
MSI-H, microsatellite high
Figure 2:
Figure 2:. Integrating Molecular Testing and Potentials Treatment Options
MMR- mismatch repair, IHC-immunohistochemistry, MSI-H microsatellite high, CNH-copy number high, CNL- copy number low
See this image and copyright information in PMC

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