FDA Approves Inavolisib for PIK3CA-Mutated HR+/HER2− MBC

The US Food and Drug Administration (FDA) has approved inavolisib (Itovebi, Genentech) in combination with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−), locally advanced or metastatic breast cancer following recurrence on or after adjuvant endocrine therapy.
The FDA also approved the FoundationOne Liquid CDx assay to identify patients who qualify for the newly approved treatment.
Genentech Executive Levi Garraway, MD, PhD, called the approval “an important new first-line option for people living with HR+ breast cancer with a PIK3CA mutation” in a company press release.
The oncogenic PIK3CA mutation is found in approximately 40% HR+ metastatic breast cancers. Novartis’ alpelisib (Piqray) also targets the mutation and carries a similar breast cancer indication for combination with fulvestrant.
Approval of inavolisib was based on the INAVO120 trial, which randomized 325 qualifying patients equally to receive either inavolisib 9 mg or placebo orally once daily on a background of palbociclib and fulvestrant in 28-day treatment cycles.
Patients had progressed during or within 12 months of completing adjuvant endocrine therapy and had not received prior systemic therapy for locally advanced or metastatic disease.
Median investigator-assessed progression-free survival was 15 months with inavolisib vs 7.3 months with placebo (hazard ratio, 0.43; P < .0001). The objective response rate (ORR) was 58% and median duration of response (DOR) was 18.4 months in the inavolisib arm vs an ORR of 25% and DOR of 9.6 months in the placebo arm. An interim analysis of overall survival did not reach statistical significance but favored inavolisib.
The most common adverse reactions with inavolisib, occurring in 20% or more of patients, were decreased neutrophils, hemoglobin, platelets, lymphocytes, calcium, potassium, sodium, magnesium, and appetite; increased fasting glucose, creatinine, and alanine aminotransferase; stomatitis; diarrhea; fatigue; nausea; rash; SARS-CoV-2 infection; and headache.
The recommended inavolisib dose is 9 mg orally once daily, with or without food, until disease progression or unacceptable toxicity.
Pricing information wasn’t available at press time; 56 tablets of alpelisib, also administered daily, costs $23,217.11, according to drugs.com.
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]
 
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