Inavolisib-Based Therapy in PIK3CA -Mutated Advanced Breast Cancer

作者：Nicholas C. Turner, Seock‐Ah Im, Cristina Saura, Dejan Juric, Sibylle Loibl, Kevin Kalinsky, Peter Schmid, Sherene Loi, Patrapim Sunpaweravong, Antonino Musolino, Huiping Li, Qingyuan Zhang, Zbigniew Nowecki, Roland Leung, Eirini Thanopoulou, Noopur Shankar, Guiyuan Lei, Thomas J. Stout, Katherine E. Hutchinson, Jennifer L. Schutzman, Chunyan Song, Komal Jhaveri · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2404625 · 被引用次数：274 · 研究领域：Advanced Breast Cancer Therapies、PI3K/AKT/mTOR signaling in cancer、HER2/EGFR in Cancer Research

Background Inavolisib is a highly potent and selective inhibitor of the alpha isoform of the p110 catalytic subunit of the phosphatidylinositol 3-kinase complex (encoded by PIK3CA ) that also promotes the degradation of mutated p110α. Inavolisib plus palbociclib–fulvestrant has shown synergistic activity in preclinical models and promising antitumor activity in early-phase trials. Methods In a phase 3, double-blind, randomized trial, we compared first-line inavolisib (at an oral dose of 9 mg once daily) plus palbociclib–fulvestrant (inavolisib group) with placebo plus palbociclib–fulvestrant (placebo group) in patients with PIK3CA -mutated, hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative locally advanced or metastatic breast cancer who had had relapse during or within 12 months after the completion of adjuvant endocrine therapy. The primary end point was progression-free survival as assessed by the investigator. Research Summary Addition of PI3K Inhibition in Breast Cancer Results A total of 161 patients were assigned to the inavolisib group and 164 to the placebo group; the median follow-up was 21.3 months and 21.5 months, respectively. The median progression-free survival was 15.0 months (95% confidence interval [CI], 11.3 to 20.5) in the inavolisib group and 7.3 months (95% CI, 5.6 to 9.3) in the placebo group (hazard ratio for disease progression or death, 0.43; 95% CI, 0.32 to 0.59; P<0.001). An objective response occurred in 58.4% of ...