US Food and Drug Administration Approval Summary: Inavolisib With Palbociclib and Fulvestrant for Endocrine-Resistant, <i>PIK3CA</i> -Mutated, Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, Locally Advanced or Metastatic Breast Cancer
Abstract
PURPOSE The US Food and Drug Administration (FDA) approved inavolisib with palbociclib and fulvestrant for adults with endocrine-resistant, PIK3CA -mutated, hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, locally advanced or metastatic breast cancer (MBC), as detected by an FDA-approved test, FoundationOne Liquid CDx assay, after recurrence on or after completing adjuvant endocrine therapy. PATIENTS AND METHODS Approval was based on INAVO120, a randomized, double-blind, placebo-controlled trial in 325 patients with endocrine-resistant, PIK3CA -mutated, hormone receptor–positive, HER2-negative, locally advanced or MBC. Patients were randomly assigned (1:1) to either inavolisib (n = 161) or placebo (n = 164) in combination with palbociclib and fulvestrant. RESULTS INAVO120 met its primary end point of progression-free survival (PFS) by investigator assessment, with a median PFS of 15.0 months for inavolisib + palbociclib + fulvestrant versus 7.3 months for placebo + palbociclib + fulvestrant (hazard ratio [HR], 0.43 [95% CI, 0.32 to 0.59]; P < .0001). The objective response rate was 58% (95% CI, 50 to 66) versus 25% (95% CI, 19 to 32). The median duration of response was 18.4 months (95% CI, 10.4 to 22.2) versus 9.6 months (95% CI, 7.4 to 16.6). Interim analysis of overall survival did not reach statistical significance but was supportive of the overall benefit-risk assessment with a HR of 0.64 (95% CI, 0.43 to 0.97). Consistent with the PI3Kα inhibitor class, common adverse reactions noted with inavolisib included hyperglycemia, stomatitis, diarrhea, and rash. CONCLUSION The approval of inavolisib with palbociclib plus fulvestrant was based on a statistically significant and clinically meaningful improvement in PFS observed in the INAVO120 trial. Before this approval, there were no specific therapies approved by the FDA for the first-line treatment of patients with endocrine-resistant, hormone receptor–positive advanced or MBC.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (18)
Suparna Wedam
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD
Preeti Narayan
US Food and Drug Administration, Silver Spring, MD
Haley Gittleman
US Food and Drug Administration, Silver Spring, MD
Joyce Cheng
Vishal Bhatnagar
Hairat Sabit
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD
Lauren S.L. Price
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD
Nam Atiqur Rahman
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD
Haw-Jyh Chiu
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD
Nikolett Biel
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD
Tiffany Ricks
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD
Mallorie Fiero
US Food and Drug Administration, Silver Spring, MD
Shenghui Tang
US Food and Drug Administration, Silver Spring, MD
Christy Osgood
US Food and Drug Administration, Silver Spring, MD
William Pierce
Center for Drug Evaluation and Research (CDER), US Food and Drug Administration, Silver Spring, MD
Richard Pazdur
From the Oncology Center of Excellence (G.U.M., R.P.) and the Office of the Commissioner (N.N.B., R.M.C.), Food and Drug Administration, Silver Spring, MD.
Paul G. Kluetz
Laleh Amiri-Kordestani