US Food and Drug Administration Approval Summary: Inavolisib With Palbociclib and Fulvestrant for Endocrine-Resistant, PIK3CA-Mutated, Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-Negative, Locally Advanced or Metastatic Breast Cancer
Cette étude analyse les données de l'essai ayant conduit la "Food and Drug Administration" à autoriser l'utilisation de l'inavolisib en combinaison avec le palbociclib et le fulvestrant pour traiter les patientes atteintes d'un cancer HR+ HER2- de stade localement avancé ou métastatique, présentant des mutations PIK3CA et résistant à un traitement endocrinien
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 PI3K
α 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.
Journal of Clinical Oncology , résumé, 2025