Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), presented today positive results from the Phase III INAVO120 study evaluating inavolisib in combination with palbociclib (Ibrance®) and fulvestrant as a first-line treatment for people with PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, endocrine-resistant, locally advanced or metastatic breast cancer.
The inavolisib combination reduced the risk of disease worsening or death (progression-free survival; PFS) by 57% compared to palbociclib and fulvestrant alone (15.0 months vs 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p<0.0001). The benefit was consistent across subgroups. Overall survival (OS) data were immature at this time, but a clear positive trend has been observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 (boundary of 0.0098)). Follow-up for OS will continue to the next analysis. Data available for other secondary endpoints at this analysis showed clinically meaningful increases in objective response rate, duration of response and clinical benefit rate.
“The importance of the PI3K pathway has long been recognized across many cancers, and inavolisib could transform the way breast cancer is treated in patients whose tumors harbor PIK3CA mutations,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “The clinically meaningful benefit observed with the inavolisib combination speaks to its potential to become a new standard of care in this patient population and builds on our commitment to improve outcomes across all types of breast cancer. We look forward to bringing inavolisib to patients as soon as possible.”
The inavolisib combination was well tolerated and adverse events were consistent with the known safety profiles of the individual study treatments, with no new safety signals observed. The most common Grade 3-4 adverse effects (≥ 5 percent) with the inavolisib combination compared to palbociclib and fulvestrant alone were neutropenia (80.2% vs 78.4%), thrombocytopenia (14.2% vs 4.3%), anemia (6.2% vs 1.9%), stomatitis (5.6% vs 0) and hyperglycemia (5.6% vs 0). The discontinuation rate in the inavolisib treatment group was 6.8% compared to 0.6% for palbociclib and fulvestrant alone.
Inavolisib, an investigational oral therapy, is currently being investigated in three Phase III clinical studies in people with PIK3CA-mutated locally advanced or metastatic breast cancer (INAVO120, INAVO121, INAVO122). PIK3CA mutations are found in approximately 40% of HR-positive breast cancers and can lead to mutated PI3Kα protein, which contributes to uncontrolled tumor growth, disease progression and resistance to endocrine-based treatment.
