The combination of inavolisib (Itovebi) with fulvestrant and palbociclib (Ibrance) has shown a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to fulvestrant and palbociclib alone in patients with hormone receptor-positive (HR+), HER2-negative (HER2–), PIK3CA-mutated breast cancer. These findings come from the latest data of the phase 3 INAVO120 study (NCT04191499), which were published in The New England Journal of Medicine.
The inavolisib regimen reduced the risk of disease progression or death by 57% compared with palbociclib alone. The median PFS was 15.0 months in the inavolisib arm compared to 7.3 months in the palbociclib arm (HR, 0.43; 95% CI, 0.32-0.59; P <.001). This PFS benefit was consistently observed across all pre-specified subgroups, including patients with disease that had spread to three or more sites.
Overall Survival Data
At the time of this analysis, overall survival (OS) data were still immature but demonstrated a positive trend. The stratified hazard ratio for OS was 0.64 (95% CI, 0.43-0.97; P =.03), suggesting a potential survival advantage with the inavolisib regimen.
Expert Commentary
"With a doubling of progression-free survival and consistent benefits in patients whose disease had spread to multiple challenging-to-treat locations, including the liver and lungs, these INAVO120 data are significant for patients," said Dr. Komal Jhaveri, MD, section head for the endocrine therapy research portfolio and clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center, and a principal investigator of the INAVO120 study. "I’m confident this inavolisib-based regimen could become a new first-line standard of care for this patient population with one of the most commonly mutated genes in metastatic breast cancer, associated with a poor prognosis."
Regulatory Approval
On October 10, 2024, the FDA approved the inavolisib regimen for patients with HR+, HER2–, locally advanced or metastatic breast cancer following recurrence on or after completing adjuvant endocrine therapy. This approval was based on the data from the INAVO120 trial.
Additional Data from ASCO
Data from INAVO120 were also presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. These results indicated that the time from randomization to the end of next-line treatment was 24.0 months with the addition of inavolisib, compared to 15.1 months for palbociclib and fulvestrant alone (HR, 0.54; 95% CI, 0.38-0.77). The time to first chemotherapy was not yet reached with the addition of inavolisib, compared to 15.0 months with placebo (unstratified HR, 0.54; 95% CI, 0.37-0.78).
Ongoing Trials
The INAVO121 (NCT05646862) and INAVO122 (NCT05894239) trials are currently evaluating different inavolisib combinations for the treatment of patients with PIK3CA-mutated breast cancer.
