A Phase III trial (INAVO120) has demonstrated that Roche's Itovebi™ (inavolisib), when combined with palbociclib and fulvestrant, more than doubled progression-free survival in patients with advanced HR-positive, HER2-negative breast cancer harboring PIK3CA mutations. The study's findings suggest a potential new first-line standard of care for this patient population.
The INAVO120 study, a Phase III trial, compared the inavolisib-based combination therapy to palbociclib and fulvestrant alone. The results, published in The New England Journal of Medicine, indicated a 57% reduction in the risk of disease progression or death (HR 0.43; 95% CI: 0.30-0.63). This statistically significant improvement led to the recent FDA approval of the Itovebi-based regimen for first-line treatment of HR-positive, HER2-negative breast cancer with a PIK3CA mutation.
Clinical Impact and Expert Opinion
Dr. Komal Jhaveri, 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, emphasized the significance of the findings: "With a doubling of progression-free survival and consistent benefits in people whose disease had spread to multiple challenging-to-treat locations, including the liver and lungs, these INAVO120 data are significant for patients. I’m confident this Itovebi-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."
Understanding the PIK3CA Mutation
The PIK3CA mutation is a common driver in HR-positive metastatic breast cancer, present in approximately 40% of cases. This mutation is associated with poorer prognosis, making the development of targeted therapies like inavolisib crucial.
Trial Design and Endpoints
The INAVO120 trial (NCT04191499) was a randomized, double-blind, placebo-controlled Phase III study. Patients with HR-positive, HER2-negative advanced breast cancer with PIK3CA mutations were enrolled. The primary endpoint was progression-free survival, while secondary endpoints included overall survival, objective response rate, and safety.
Roche's Expanding Breast Cancer Portfolio
In addition to the success of inavolisib, Roche, through its Genentech division, is actively expanding its breast cancer portfolio. Recently, Genentech announced a deal with Regor Pharmaceuticals to acquire next-generation CDK inhibitors, further demonstrating their commitment to developing novel breast cancer therapies.
