Genentech's Itovebi™ (inavolisib)-based regimen has demonstrated a statistically significant and clinically meaningful benefit in patients with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. The Phase III INAVO120 study, published in the New England Journal of Medicine, revealed a 57% reduction in the risk of disease worsening or death compared to palbociclib and fulvestrant alone.
The U.S. Food and Drug Administration (FDA) recently approved Itovebi in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, following recurrence on or after completing adjuvant endocrine therapy. This approval marks a significant advancement in the treatment landscape for this patient population.
INAVO120 Study Results
The INAVO120 study (NCT04191499) included 325 patients and showed that the Itovebi-based regimen significantly improved progression-free survival (PFS). The median PFS was 15.0 months in the Itovebi arm compared to 7.3 months in the palbociclib and fulvestrant arm (HR=0.43, 95% CI: 0.32-0.59, p<0.0001). This PFS benefit was consistent across all pre-specified subgroups, including patients with disease spread to three or more locations.
"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," said Komal Jhaveri, M.D., section head for the endocrine therapy research portfolio and clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center and one of the principal investigators of the INAVO120 study. "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."
Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338). Follow-up for OS will continue to the next analysis.
The Significance of PIK3CA Mutations
The PIK3CA mutation is found in approximately 40% of HR-positive metastatic breast cancers and is associated with a poor prognosis. Early biomarker testing with an FDA-approved test, such as Foundation Medicine’s FoundationOne®Liquid CDx, before first-line treatment is crucial to help identify people who may benefit from targeted therapy, such as Itovebi.
Ongoing Research
Itovebi is currently being investigated in three company-sponsored Phase III clinical studies (INAVO120, INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations. These studies aim to further explore the potential of Itovebi in improving outcomes for patients with this specific type of breast cancer.
Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development, stated, "Publication of these Phase III results in the New England Journal of Medicine further highlights the transformative potential of the Itovebi-based regimen. This new treatment exemplifies our ambition to target specific disease pathways more effectively and improve outcomes in people with breast cancer, while also emphasizing the importance of comprehensive testing for mutations like PIK3CA at the time of diagnosis."
