The promise of combining CDK4/6 inhibition with hormonal therapy in the first-line treatment setting for metastatic or recurrent endometrial adenocarcinoma.

Metastatic or recurrent endometrioid adenocarcinoma of the uterine corpus is often incurable with limited treatment options. First-line treatment often includes cytotoxic chemotherapy, which incurs significant toxicities for many patients. Endometrial cancer, specifically endometrioid cancer, is a hormone-sensitive disease and, while single-agent hormonal therapies have demonstrated clinical benefit, resistance to these agents often leads to the use of chemotherapy. There is a lack of approved endocrine treatment options in the metastatic setting for most recurrent endometrial cancers, representing an unmet clinical need. Emerging evidence suggests that hormonal therapy in combination with other targeted treatments, such as cyclin dependent kinase (CDK)4/6 inhibitors, is well tolerated and effective in select patient populations. We discuss the clinical evidence suggesting that the combination of CDK4/6 inhibitors and hormonal therapy has the potential to represent an important addition to the first-line treatment options for patients with low-grade advanced or recurrent endometrial cancer.

Informations de copyright

© IGCS and ESGO 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: The authors disclose the following potential conflicts of interest: IR-C: Grants or contracts from any entity: MSD, Roche, BMS, Novartis, AstraZeneca, Merck Sereno; Consulting fees: Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis, Adaptimmun, DAICHI Sankyo, ESAI, Immunogen, Seagen, Blueprint, Takeda, Chugai; Travel support: Roche, AstraZeneca, MSD, ESAI, GSK; Participation on a Data Safety Monitoring Board or Advisory Board: Athena, ATTEND, AGOOVAR57; MITO25; Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid: Chair GINECO. DL: Consulting fees: AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis, PharmaMar; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: AstraZeneca, Clovis Oncology, GSK, MSD, PharmaMar; Payment for expert testimony: Clovis Oncology; Support for attending meetings and/or travel: AstraZeneca, Clovis Oncology, GSK; Participation on a Data Safety Monitoring Board or Advisory Board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro, AstraZeneca, GSK; Leadership or fiduciary role in other board, society, committee, or advocacy group, unpaid: GCIG, Member, Board of Directors; Receipt of equipment, materials, drugs, medical writing, gifts, or other services (payments made to institution): Clovis Oncology, GSK, MSD, PharmaMar; Institutional funding for work in clinical trials: AstraZeneca, Clovis Oncology, GSK, MSD, Genmab, PharmaMar, Seagen, Immunogen, Novartis, Roche, Incyte. VU: Stock or stock options: EQRx. RG: Stock or stock options: EQRx, Ironwood Pharmaceuticals, Cyclerion. AH: Stock or stock options: EQRx, Bolt Biotherapeutics, Roche. BJM: Consulting fees: 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, Zentalis; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: AstraZeneca, Easai, Myriad, Roche/Genentech, TESARO/GSK. BS: Consulting fees: AstraZeneca, Clovis, GSK, Genentech, Lilly, Novartis, Gilead, Seagen, Karyopharm, Addy, Circulogene, GOG Foundation, Merck, Imvax, EQRx, Nuvation; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events: Seagen. The remaining authors declare no conflicts of interest.