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Inavolisib, Palbociclib And Fulvestrant As Potential New Standard of Care for Patients With PIK3CA-Mutated, HR-Positive, HER2-Negative Breast Cancer
According to primary analysis results from the phase 3 INAVO120 trial, the addition of inavolisib, a highly potent and selective PI3K catalytic subunit α isoform protein, to palbociclib plus fulvestrant significantly improved investigator-assessed progression-free survival (PFS) among patients with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer.
“More effective treatments for patients with endocrine-resistant, PIK3CA-mutated, [HR]-positive, HER2-negative breast cancer that prevent or overcome resistance are needed,” stated Komal L. Jhaveri, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors. “The inavolisib first-in-human study showed that the triplet had a manageable safety profile, lack of drug–drug interactions, and promising preliminary antitumor activity.”
In this randomized, double-blind study, 325 patients who relapsed during or within 12 months of adjuvant endocrine therapy completion were randomized to receive 9 mg of once daily inavolisib or placebo on days 1 to 28 of each cycle followed by per-label administration of palbociclib and fulvestrant. The primary end point was investigator-assessed PFS. Secondary end points included overall survival (OS) and confirmed objective response rate (ORR).
At a median follow up of 21.3 months, median investigator-assessed PFS was 15 months in the inavolisib arm and 7.3 months in the placebo arm. Investigator-assessed PFS at 6, 12, and 18 months in the inavolisib arm was 82.9%, 55.9%, and 46.2% vs 55.9%, 32.6%, and 21.1% in the placebo arm, respectively. OS results trended in favor of inavolisib (hazard ratio [HR] 0.64; 95% confidence interval 0.43 to 0.97; P = .0338). OS event-free rates at 12 and 18 months were 85.9% and 73.7% in the inavolisib arm and 74.9% and 67.5% in the placebo arm. Confirmed ORR was 58.4% in the inavolisib arm and 25% in the placebo arm.
The most common grade 3/4 adverse events included neutropenia, hyperglycemia, diarrhea, stomatitis, mucosal inflammation, and rash. Treatment discontinuation due to adverse events occurred in 6.2% of patients in the inavolisib arm and 0.6% of patients in the placebo arm. No treatment-related grade 5 adverse events were reported.
This triplet therapy “could represent a new standard of care for [patients] with PIK3CA-mutated, [HR-positive, HER2-negative locally advanced or metastatic breast cancer],” concluded Dr Jhaveri and coauthors.
Source:
Jhaveri KL, Im SA, Saura C, et al. Inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: Phase III INAVO120 primary analysis. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023. San Antonio, Texas. Abstract GS03-13
