Laura M Spring1, Seth A Wander1, Mark Zangardi1, Aditya Bardia2. 1. Massachusetts General Hospital Cancer Center, Harvard Medical School, Lawrence House 304, 10 North Grove St, Boston, MA, 02114, USA. 2. Massachusetts General Hospital Cancer Center, Harvard Medical School, Lawrence House 304, 10 North Grove St, Boston, MA, 02114, USA. Bardia.Aditya@mgh.harvard.edu.
Abstract
PURPOSE OF REVIEW: To describe the clinical role of CDK 4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer (HR+ MBC) as well as current controversies and evolving areas of research. RECENT FINDINGS: Palbociclib, ribociclib, and abemaciclib are each approved in combination with an aromatase inhibitor or fulvestrant for HR+ MBC. Abemaciclib is also approved as monotherapy for pre-treated patients. Key questions in the field include whether all patients with HR+ MBC should receive a CDK 4/6 inhibitor up front versus later line, impact on overall survival, role of continued CDK 4/6 blockade, mechanism of clinical resistance, and treatment sequencing. The development of CDK 4/6 inhibitors has changed the therapeutic management of HR+ MBC. Additional research is needed to determine optimal treatment sequencing, understand mechanisms governing resistance, and develop novel therapeutic strategies to circumvent or overcome clinical resistance and further improve the outcomes of patients with MBC.
PURPOSE OF REVIEW: To describe the clinical role of CDK 4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer (HR+ MBC) as well as current controversies and evolving areas of research. RECENT FINDINGS:Palbociclib, ribociclib, and abemaciclib are each approved in combination with an aromatase inhibitor or fulvestrant for HR+ MBC. Abemaciclib is also approved as monotherapy for pre-treated patients. Key questions in the field include whether all patients with HR+ MBC should receive a CDK 4/6 inhibitor up front versus later line, impact on overall survival, role of continued CDK 4/6 blockade, mechanism of clinical resistance, and treatment sequencing. The development of CDK 4/6 inhibitors has changed the therapeutic management of HR+ MBC. Additional research is needed to determine optimal treatment sequencing, understand mechanisms governing resistance, and develop novel therapeutic strategies to circumvent or overcome clinical resistance and further improve the outcomes of patients with MBC.
Entities:
Keywords:
Abemaciclib; Clinical trials; Cyclin-dependent kinases 4 and 6; Metastatic breast cancer; Palbociclib; Resistance mechanisms; Ribociclib
Authors: Daniel A Cehic; Aaron L Sverdlov; Bogda Koczwara; Jon Emery; Doan T M Ngo; Elysia Thornton-Benko Journal: Curr Treat Options Oncol Date: 2021-10-21
Authors: Seth A Wander; Ofir Cohen; Xueqian Gong; Gabriela N Johnson; Jorge E Buendia-Buendia; Maxwell R Lloyd; Dewey Kim; Flora Luo; Pingping Mao; Karla Helvie; Kailey J Kowalski; Utthara Nayar; Adrienne G Waks; Stephen H Parsons; Ricardo Martinez; Lacey M Litchfield; Xiang S Ye; Chunping Yu; Valerie M Jansen; John R Stille; Patricia S Smith; Gerard J Oakley; Quincy S Chu; Gerald Batist; Melissa E Hughes; Jill D Kremer; Levi A Garraway; Eric P Winer; Sara M Tolaney; Nancy U Lin; Sean G Buchanan; Nikhil Wagle Journal: Cancer Discov Date: 2020-05-13 Impact factor: 39.397