Inavolisib Combination Doubles PFS in PIK3CA Mutated Advanced Breast Cancer

The Phase III INAVO120 trial showed that the new targeted therapy, inavolisib (Itovebi), provides significant survival benefits for PIK3CA-mutated HR-positive/HER2-negative advanced breast cancer. According to data released at the 2025 ASCO Annual Meeting, adding inavolisib to palbociclib and fulvestrant reduced the risk of death by over 30% and extended median survival from 27 to 34 months. Progression-free survival nearly doubled, and the time to chemotherapy was delayed by two years.

Genentech announced positive final results for inavolisib from the Phase III INAVO120 study at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The data, also published in NEJM, showed that inavolisib, in combination with palbociclib and fulvestrant, reduced the risk of death by more than 30%. This represents a statistically significant and clinically meaningful improvement in overall survival for PIK3CA-mutated, HR-positive, HER2-negative metastatic breast cancer.

The results mark the first time a PI3K pathway-targeted drug has demonstrated an improvement in overall survival for people with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer.

A Potential New Standard of Care

“The landmark data for the inavolisib-based regimen showed not only a doubling in progression-free survival, but importantly that it extended lives and gave people more time without chemotherapy,” said Dr Nicholas Turner, lead study author and professor of medical oncology at The Royal Marsden NHS FT, UK. “These results give us confidence that this regimen could become the new standard of care in the first-line setting, having demonstrated a substantial benefit on patient outcomes and quality of life.”

The PIK3CA gene mutation, present in roughly 40% of this breast cancer subtype, is linked to poorer outcomes and resistance to endocrine therapy. The new findings suggest that adding inavolisib to standard treatment can alter the trajectory for these patients.

Key Findings from the INAVO120 Study

The trial involved 325 patients whose disease had progressed during or shortly after endocrine therapy. Participants received either inavolisib plus palbociclib and fulvestrant or placebo plus palbociclib and fulvestrant.

• Median overall survival reached 34 months in the inavolisib group, compared with 27 months in the control group (hazard ratio 0.67; p=0.0190).
• Median progression-free survival nearly doubled, from 7.3 months with standard treatment to 17.2 months with inavolisib (hazard ratio 0.42).
• The combination also improved the objective response rate—the percentage of patients with significant tumor shrinkage—and delayed the time to chemotherapy by approximately two years.

Notably, these benefits came without new safety concerns. Treatment was generally well tolerated, with few discontinuations due to side effects. “For the first time, a PI3K pathway-targeted drug has shown it can help people with this breast cancer subtype live longer,” said Dr. Levi Garraway, Genentech’s CMO and head of Global Product Development. “Itovebi exemplifies our continued commitment to improve survival rates for people with this common PIK3CA mutation, for whom more effective treatment options are needed.”

What’s Next?

Inavolisib is already under investigation in three additional Phase III studies exploring its use in various settings of PIK3CA-mutated, advanced breast cancer, including comparisons with alpelisib, combinations with dual HER2 blockade, and first-line treatment regimens.