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

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.