INAVO120: Inavolisib Delays Chemotherapy and Boosts OS in HR+/HER2– aBC

According to an abstract from the 2025 American Society of Clinical Oncology (ASCO), updated results from the final OS analysis of the phase 3 INAVO120 trial (NCT04191499) revealed that the addition of the phosphatidylinositol-3-kinase alpha (PI3Kα) inhibitor, inavolisib (INAVO), to the combination of palbociclib (PABLO) and fulvestrant (FULV) demonstrated a statistically significant improvement in overall survival (OS) when compared with the use of placebo (PBO) plus palbociclib and fulvestrant in patients with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative, endocrine-resistant advanced breast cancer.

In a press release, lead author, Dr. Nicholas Turner, Royal Marsden Hospital and Institute of Cancer, London, United Kingdom stated, “The INAVO120 study was designed to address a need for more potent and tolerable therapies for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the first-line setting.  The INAVO120 trial findings support an inavolisib-based regimen as an emerging new standard of care that helps people live longer, as well as substantially improving how long treatment works.”

The study consisted of 325 patients with PIK3CA-mutated, HR-positive, HER2-negative locally advanced, or metastatic breast cancer that progressed during or after hormone therapy. Participants were randomly assigned to receive either INAVO along with PABLO and FULV (161 patients) or a PBO combined with PABLO and FULV (164 patients).

Results revealed that at a median follow-up of 34.2 months, the median OS was reported as 34.0 months with the INAVO arm compared to 27.0 months with the PBO arm. The OS rates at 6, 12, 18, 24, and 30 months for the inavolisib arm were 96.8%, 87.0%, 74.3%, 65.8%, and 56.5%, respectively. In the placebo arm, the corresponding rates were 90.1%, 76.7%, 67.2%, 56.3%, and 46.3%.

The overall response rate (ORR) was 62.7% and 28.0% for INAVO and PBO, respectively, and the median time for chemotherapy (TTC) was 35.6 months in the INAVO arm versus 12.6 months in the PBO arm. The updated median investigator-assessed progression-free survival (INV-PFS) was 17.2 months in the INAVO arm and 7.3 months in the PBO arm, with landmark analyses supporting the durability of the benefit. Regarding adverse events (AEs), 90.7% of patients in the INAVO arm and 84.7% in the PBO arm experienced grade 3 or 4 AEs. There were no new grade 5 AEs; 63.4% and 13.5% experienced any grade hyperglycemia and AEs that resulted in discontinuation of INAVO and PBO in 6.8% and 0.6% of patients, respectively.

The researchers concluded that INAVO + PALBO + FULV demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit compared to PBO + PALBO + FULV, with sustained invasive progression-free survival (iPFS) benefits over extended follow-up and a substantial overall response rate (ORR) increase. Adding INAVO to PALBO + FULV notably delayed TTC ( by  ~2 years).  Moreover, with prolonged exposure, no new safety signals or changes in the safety profile were observed, reinforcing its good tolerability as demonstrated in the low rates of AE-related discontinuation.