FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer

Regulatory approval: On Oct 10, 2024, the FDA approved inavolisib (Itovebi) in combination with palbociclib and fulvestrant for adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy. Approval was supported by INAVO120, which showed improved investigator-assessed PFS versus placebo plus palbociclib/fulvestrant; interim OS analysis did not reach statistical significance.

FDA approval (Oct 10, 2024)

The FDA approved inavolisib (Itovebi; Genentech) with palbociclib and fulvestrant for adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy.

The FDA also approved FoundationOne Liquid CDx as a companion diagnostic to identify patients with breast cancer for treatment with inavolisib plus palbociclib and fulvestrant.

Key efficacy evidence: INAVO120 (NCT04191499)

INAVO120 was a randomized, double-blind, placebo-controlled multicenter trial (n=325) in patients whose disease progressed during or within 12 months of completing adjuvant endocrine therapy and who had not received prior systemic therapy for locally advanced/metastatic disease.

  • Median PFS (investigator-assessed, RECIST 1.1): 15.0 vs 7.3 months (HR 0.43; 95% CI 0.32–0.59; p<0.0001)
  • ORR: 58% vs 25%
  • Median DOR: 18.4 vs 9.6 months
  • Interim OS (63% information fraction): not statistically significant; HR 0.64 (95% CI 0.43–0.97)

Safety and dosing highlights

Common adverse reactions (≥20%), including lab abnormalities, included decreased neutrophils/hemoglobin/platelets/lymphocytes, increased fasting glucose, stomatitis, diarrhea, fatigue, rash, and others. Recommended inavolisib dose: 9 mg orally once daily until progression or unacceptable toxicity.

The review was conducted under Project Orbis; reviews at partner agencies were ongoing at the time of the FDA communication.

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