Phase Ib Study of Ribociclib plus Fulvestrant and Ribociclib plus Fulvestrant plus PI3K Inhibitor (Alpelisib or Buparlisib) for HR+ Advanced Breast Cancer

Abstract Purpose: Resistance to treatment with endocrine therapy in patients HR+, HER2? advanced breast cancer (ABC) is common and dual inhibition of CDK4/6 PI3K pathways may delay the development resistance. This phase Ib trial evaluates safety tolerability triple double regimens containing inhibitor ribociclib. Patients Methods: In this open-label, multicenter, study, 70 postmenopausal women ABC were enrolled into one four combinations: ribociclib (once daily, 3 weeks on, 1 week off) plus fulvestrant; (continuous dosing) alpelisib or buparlisib fulvestrant. Results: The recommended II dose (RP2D) was confirmed be 600 mg (3 400 fulvestrant 500 mg. For combination buparlisib, RP2D 30 Enrollment for combinations stopped due unexpected toxicity. No determined combination. profiles consistent those previous studies. There no marked difference exposure presence triple-combination partners. highest overall response rate seen (25.0%; 95% confidence interval, 9.8–46.7). Conclusions: Ribociclib demonstrated ABC. Triple are not investigation. See related commentary by Clark et al., p. 371