Konstantinopoulos Panagiotis A, Xiong Niya, Krasner Carolyn, Liu Joyce F, Sawyer Hannah, Polak Madeline, Needham Hope, Geddes Megan, Koppermann Lani, Shea Meghan, Castro Cesar, Cheng Su-Chun, Matulonis Ursula A, Lee Elizabeth K
Dana-Farber Cancer Institute, Boston, MA, USA.
Beth Israel Deaconess Medical Center, Boston, MA, USA.
Gynecol Oncol Rep. 2024 Feb 22;52:101348. doi: 10.1016/j.gore.2024.101348. eCollection 2024 Apr.
Several lines of preclinical evidence indicate that combining PI3K and CDK4/6 inhibitors may further enhance the efficacy of hormonal therapy by overcoming and acquired resistance to PI3K and CDK4/6 blockade. We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally available, selective inhibitor of the class I PI3K isoforms and mTORC1/2) in recurrent endometrial cancer (EC). This study was terminated prematurely after 5 patients initiated protocol therapy due to discontinuation of further development of LY3023414. We report our findings from these patients, including one with recurrent endometrioid EC with and hotspot mutations who had previously progressed through letrozole/everolimus and achieved a partial response to letrozole/abemaciclib/LY3023414.
多项临床前证据表明，联合使用PI3K和CDK4/6抑制剂可能通过克服对PI3K和CDK4/6阻断的原发性和获得性耐药，进一步提高激素疗法的疗效。我们评估了阿贝西利、来曲唑和LY3023414（一种口服可用的I类PI3K亚型和mTORC1/2选择性抑制剂）联合用于复发性子宫内膜癌（EC）的情况。由于LY3023414停止进一步研发，在5例患者开始方案治疗后，本研究提前终止。我们报告这些患者的研究结果，包括1例复发性子宫内膜样EC患者，该患者存在原发性和热点突变，此前接受来曲唑/依维莫司治疗病情进展，而接受来曲唑/阿贝西利/LY3023414治疗后获得部分缓解。
