Author(s): Komal L. Jhaveri, M.D.1,2; Seock-Ah Im, M.D., Ph.D.3; Cristina Saura, M.D., Ph.D.4; Sibylle Loibl, M.D., Ph.D.5,6; Kevin Kalinsky, M.D.7; Peter Schmid, M.D., Ph.D.8; Sherene Loi, M.D., Ph.D.9,10; Eirini Thanopoulou, M.D., Ph.D.11; Noopur Shankar, M.D., Ph.D.12; Yanling Jin, Ph.D.13; Thomas J. Stout, Ph.D.12; Tiffany D. Clark, Ph.D.12; Chunyan Song, M.D.12; Dejan Juric, M.D.14; Nicholas C. Turner, M.D., Ph.D.15;
BACKGROUND
In the phase 3, double-blind, randomized INAVO120 trial, treatment with inavolisib plus palbociclib–fulvestrant led to a significant progression-free survival benefit, as compared with placebo plus palbociclib–fulvestrant, among 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 completion of adjuvant endocrine therapy.
METHODS
We randomly assigned patients with PIK3CA-mutated, hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer who had had disease recurrence or progression during or within 12 months after completion of adjuvant endocrine therapy to receive inavolisib plus palbociclib–fulvestrant (inavolisib group) or placebo plus palbociclib–fulvestrant (placebo group). In the current report, we provide the results of the final analysis of overall survival, including updated data on efficacy and safety.
RESULTS
A total of 161 patients were assigned to the inavolisib group, and 164 to the placebo group. After a median follow-up of 34.2 months in the inavolisib group and 32.3 months in the placebo group, the median overall survival was 34.0 months (95% confidence interval [CI], 28.4 to 44.8) with inavolisib and 27.0 months (95% CI, 22.8 to 38.7) with placebo (hazard ratio for death, 0.67; 95% CI, 0.48 to 0.94; P=0.02 [prespecified boundary for statistical significance, P<0.0469]). An objective response occurred in 62.7% (95% CI, 54.8 to 70.2) of patients in the inavolisib group and 28.0% (95% CI, 21.3 to 35.6) of those in the placebo group (P<0.001). The updated hazard ratio for disease progression or death was 0.42 (95% CI, 0.32 to 0.55). Adverse events led to discontinuation of inavolisib in 6.8% of patients and discontinuation of placebo in 0.6%. The incidence of hyperglycemia, stomatitis or mucosal inflammation, gastrointestinal toxic effects (e.g., diarrhea), and ocular toxic effects (e.g., dry eye and blurred vision) was higher with inavolisib than with placebo.
CONCLUSIONS
Treatment with inavolisib plus palbociclib–fulvestrant led to a significant overall survival benefit, as compared with placebo plus palbociclib–fulvestrant. Hyperglycemia, stomatitis or mucosal inflammation, gastrointestinal toxic effects, and ocular toxic effects were reported more frequently with inavolisib than with placebo. (Funded by F. Hoffmann–La Roche; INAVO120 ClinicalTrials.gov number, NCT04191499.)
Author Affiliations
1Breast and Early Drug Development Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York; 2Weill Cornell Medical College, New York; 3Seoul National University Hospital, Seoul National University College of Medicine, Cancer Research Institute, Seoul National University, Seoul, South Korea; 4Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona; 5German Breast Group, Neu-Isenburg, Frankfurt, Germany; 6Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt, Germany; 7Winship Cancer Institute at Emory University, Atlanta; 8Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London; 9Division of Cancer Research and Clinical Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; 10Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, Parkville, VIC, Australia; 11Roche, Welwyn Garden City, United Kingdom; 12Genentech, San Francisco; 13Hoffmann–La Roche, Mississauga, ON, Canada; 14Mass General Cancer Center, Department of Medicine, Harvard Medical School, Boston; 15Royal Marsden Hospital and Institute of Cancer Research, London;
