Response to first line platinum-based chemotherapy in mismatch repair deficient (MMRd)/ microsatellite instability high (MSI-high) endometrial carcinoma

• Published in: Gynecologic oncology 2023-02, Vol.169, p.78-84
• Main Authors: Colomba, Emeline, Alexandre, Jérôme, Le Teuff, Gwénaël, Genestie, Catherine, Coupez, Dahna, Coquard, Isabelle Ray, Brachet, Pierre Emmanuel, de Percin, Sixtine, Sajous, Christophe, Fabbro, Michel, Delanoy, Nicolas, Joly, Florence, Frenel, Jean Sebastien, Pautier, Patricia, Leary, Alexandra
• Format: Article
• Language: English
• Subjects: Chemotherapy; Colorectal Neoplasms - pathology; DNA Mismatch Repair; DNA repair; Endometrial carcinoma; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - genetics; Female; Humans; Immunotherapy; Life Sciences; Microsatellite Instability; MMR; MMRd/MSI-H; Platinum - therapeutic use; Retrospective Studies
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2022.11.029

Around 15% of metastatic endometrial carcinoma (EC) are MMRd/MSI-H improving response to immune checkpoint inhibitors (ICI). So far, few data existed considering the chemotherapy (CT) sensitivity in MMRd/MSI-H EC, especially response to first-line platinum-based treatment. We performed a multicentric retrospective analysis reporting the response to first line platinum CT in MMRd/MSI-H EC patients. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) with first line platinum-based CT. A total of 112 patients MMRd/MSI-H EC from 8 centers were identified. Median overall survival was 58.0 months (95% CI: 45.3–95.1). Among them, 78 patients received first line platinum CT in recurrent/metastatic setting. With a median follow up of 32.6 months (min: 0.03; max: 135.0), ORR and DCR (disease control rate) were 50% (95% CI: 38.5–61.5) and 68% (95% CI: 56.4–78.1), respectively. Median PFS and OS from first line platinum-based CT was 7.8 months (95% CI: 6.0–9.0) and 51.9 months (95% CI: 28.0-NE), respectively. Median PFS with ICI in second line (n = 48) was 10.7 months (95% CI: 3.4-NE) from ICI initiation. ORR in first line metastatic MMRd/MSI-H EC is consistent with efficacy in an all comer metastatic EC population. •Approximately, 30% of primary endometrial cancers are MMRd/MSI-H.•In this population, PD-1 and PDL-1 inhibitors therapy have shown response rates between 40 and 60%.•However their response to 1st line platinum is unknown.•We report that the response rate is similar to an all-comer population but PFS is shorter than expected.