Inavolisib Regimen Approved for Certain Treatment-resistant Breast Cancers
The PI3K inhibitor is approved as part of combination therapy for certain patients whose breast cancer recurred on or after endocrine therapy.
The U.S. Food and Drug Administration (FDA) approved inavolisib (Itovebi), in combination with palbociclib (Ibrance) and fulvestrant (Faslodex), for patients with locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer that harbors a mutation in the PIK3CA gene and has recurred on or after prior adjuvant endocrine therapy.
Inavolisib is a targeted therapy that kills cancer cells by inhibiting the cancer-promoting activity of mutated PI3K proteins, including the protein encoded by the PIK3CA gene. PIK3CA mutations are present in approximately 35% to 40% of HR-positive breast cancers and have been implicated in resistance to endocrine therapy. This is the first FDA approval for inavolisib. Another PI3K-targeted drug, alpelisib (Piqray), was approved in 2019, in combination with fulvestrant, to treat certain patients with endocrine-resistant, HR-positive, HER2-negative, PIK3CA-mutated breast cancer.
Palbociclib inhibits CDK4 and CDK6, proteins that can fuel cancer growth. Fulvestrant is an endocrine therapy that blocks the hormone signaling that can drive HR-positive breast cancers.
The approval of inavolisib was based on results from INAVO120, a randomized, double-blind, placebo-controlled, multicenter phase II/III clinical trial. The study enrolled 325 patients with PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer whose cancer progressed on adjuvant endocrine therapy or within 12 months of completing adjuvant endocrine therapy. Enrolled patients had not received prior systemic therapy to treat locally advanced or metastatic cancer. Patients were randomly assigned (1:1) to receive palbociclib and fulvestrant combined with either inavolisib or placebo.
Fifty-eight percent of patients in the inavolisib arm experienced a treatment response, as compared with 25% of patients in the placebo arm. Further, patients in the inavolisib arm were 57% less likely to have experienced disease progression or death within 36 months than those in the placebo arm, with median progression-free survival of 15 months and 7.3 months, respectively. These results were presented at the 2023 San Antonio Breast Cancer Symposium, co-organized by the American Association for Cancer Research (AACR), and were discussed on the AACR blog.
The recommended inavolisib dose is 9 mg once per day until disease progression or unacceptable toxicity. For palbociclib, the recommended dose is 125 mg once daily in 28-day cycles (21 days on the drug, 7 days off); for fulvestrant, the recommended dose varies based on several treatment-specific and patient-specific factors.
Breast cancer is the most common nonskin cancer diagnosed in women in the United States. Breast cancer is classified into subtypes based on the cell surface expression of HR and HER2. The HR-positive, HER2-negative subtype accounts for approximately 70% of all breast cancers. According to federal statistics, it was estimated that 310,720 individuals would be diagnosed with breast cancer and 42,250 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on October 10, 2024.
