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FDA Approval of Inavolisib (Itovebi) for PIK3CA-Mutated Breast Cancer
On October 10, 2024, the Food and Drug Administration authorized inavolisib (Itovebi, Genentech, Inc.) in conjunction with palbociclib and fulvestrant for adults diagnosed with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced, or metastatic breast cancer, as identified by an FDA-approved assay, subsequent to recurrence following the completion of adjuvant endocrine therapy.
The FDA authorized the FoundationOne Liquid CDx assay as a companion diagnostic to identify breast cancer patients eligible for therapy with inavolisib, palbociclib, and fulvestrant.
Efficacy and Safety
The efficacy was assessed in INAVO120 (NCT04191499), a randomized, double-blind, placebo-controlled, multicenter trial involving 325 patients with endocrine-resistant, PIK3CA-mutated HR-positive, HER2-negative locally advanced or metastatic breast cancer, whose disease progressed during or within 12 months of completing adjuvant endocrine therapy and who had not previously received systemic therapy for locally advanced or metastatic disease.
Primary endocrine resistance is characterized by relapse during the initial two years of adjuvant endocrine therapy (ET), whereas secondary endocrine resistance is identified as relapse during adjuvant ET after a minimum of two years or relapse within twelve months of concluding adjuvant ET.
Patients were randomized in a 1:1 ratio to receive either inavolisib 9 mg or a placebo orally once daily, alongside palbociclib 125 mg orally once daily for 21 consecutive days, followed by a 7-day treatment hiatus, constituting a 28-day cycle. Fulvestrant 500 mg was administered intramuscularly on Days 1 and 15 of Cycle 1, and subsequently on Day 1 of each 28-day cycle.
Patients underwent treatment until illness progression or intolerable toxicity occurred. Randomization was stratified based on the existence of visceral disease (yes or no), type of endocrine resistance (primary or secondary), and geographic region (North America/Western Europe, Asia, other).
The primary effectiveness endpoint was investigator-evaluated progression-free survival (PFS) according to RECIST version 1.1. Supplementary efficacy outcome variables encompassed overall survival (OS), investigator-evaluated objective response rate (ORR), and duration of response (DOR). The median progression-free survival (PFS) was 15.0 months (95% CI: 11.3, 20.5) for the inavolisib + palbociclib + fulvestrant group, compared to 7.3 months (95% CI: 5.6, 9.3) for the placebo + palbociclib + fulvestrant group (Hazard ratio 0.43 [95% CI: 0.32, 0.59], p-value <0.0001).
The objective response rate (ORR) was 58% (95% CI: 50, 66) in the inavolisib + palbociclib + fulvestrant group and 25% (95% CI: 19, 32) in the placebo + palbociclib + fulvestrant group. The median duration of response (DOR) was 18.4 months (95% confidence interval: 10.4, 22.2) and 9.6 months (95% confidence interval: 7.4, 16.6), respectively. The interim analysis of overall survival, utilizing 63% of the information fraction, did not achieve statistical significance; however, it supported the overall benefit-risk assessment, yielding a hazard ratio of 0.64 (95% CI: 0.43, 0.97).
The predominant adverse reactions (≥20%), encompassing laboratory abnormalities, included reduced neutrophils, diminished hemoglobin, elevated fasting glucose, decreased platelets, lowered lymphocytes, stomatitis, diarrhea, reduced calcium, fatigue, decreased potassium, increased creatinine, elevated ALT, nausea, diminished sodium, decreased magnesium, rash, reduced appetite, COVID-19 infection, and headache.
The advised dosage of inavolisib is 9 mg administered orally once daily, with or without food, until illness progression or intolerable toxicity occurs. Consult the prescription literature for dosing details on palbociclib and fulvestrant.
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About Dr. Nishant Mittal
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. Significant contributions to stem cell biology, developmental biology, and innovative research techniques mark his career. Research Highlights Dr. Mittal's research has focused on several key areas: 1) Cardio…
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