Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer
- Author(s)
- Turner, NC; Im, SA; Saura, C; Juric, D; Loibl, S; Kalinsky, K; Schmid, P; Loi, S; Sunpaweravong, P; Musolino, A; Li, H; Zhang, Q; Nowecki, Z; Leung, R; Thanopoulou, E; Shankar, N; Lei, G; Stout, TJ; Hutchinson, KE; Schutzman, JL; Song, C; Jhaveri, KL;
- Details
- Publication Year 2024-10-31,Volume 391,Issue #17,Page 1584-1596
- Journal Title
- New England Journal of Medicine
- Publication Type
- Research article
- Abstract
- 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. 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 the patients in the inavolisib group and in 25.0% of those in the placebo group. The incidence of grade 3 or 4 neutropenia was 80.2% in the inavolisib group and 78.4% in the placebo group; grade 3 or 4 hyperglycemia, 5.6% and 0%, respectively; grade 3 or 4 stomatitis or mucosal inflammation, 5.6% and 0%; and grade 3 or 4 diarrhea, 3.7% and 0%. No grade 3 or 4 rash was observed. Discontinuation of any trial agent because of adverse events occurred in 6.8% of the patients in the inavolisib group and in 0.6% of those in the placebo group. CONCLUSIONS: In patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, inavolisib plus palbociclib-fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib-fulvestrant, with a greater incidence of toxic effects. The percentage of patients who discontinued any trial agent because of adverse events was low. (Funded by F. Hoffmann-La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.).
- Publisher
- Massachusetts Medical Society
- Keywords
- Adult; Aged; Female; Humans; Middle Aged; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects; *Breast Neoplasms/drug therapy/genetics/pathology/mortality; *Class I Phosphatidylinositol 3-Kinases/genetics/antagonists & inhibitors; Double-Blind Method; Kaplan-Meier Estimate; Mutation; Piperazines/therapeutic use/adverse effects; Progression-Free Survival; Pyridines/therapeutic use/adverse effects; Male; *Breast Neoplasms, Male/drug therapy/genetics/mortality/pathology; *Phosphoinositide-3 Kinase Inhibitors/administration & dosage/adverse effects; Imidazoles/administration & dosage/adverse effects; Oxazoles/administration & dosage/adverse effects
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1056/NEJMoa2404625
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-01-14 02:50:41
Last Modified: 2025-01-14 02:50:52