Adding inavolisib to palbociclib and fulvestrant significantly improved overall survival (OS) for patients with PIK3CA-mutated HR+, HER2- endocrine-resistant advanced breast cancer, according to the final analysis of the INAVO120 trial, presented at the 2025 ASCO Annual Meeting. 

“The INAVO120 study was designed to address a need for more potent and tolerable therapies for PIK3CA-mutated, HR+, HER2- 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.”  

- Nicholas C. Turner, MD, PhD, of the Royal Marsden Hospital in London, lead study author, stated in a press release. 

Researchers evaluated 325 patients with PIK3CA-mutated, HR+, HER2- advanced or metastatic breast cancer who received once-daily inavolisib or placebo, plus 125 mg of palbociclib for the first 21 days of a cycle and 500 mg of fulvestrant on day 1 and day 15 of the cycle and every 4 weeks. The patients were followed for a median of 34.2 months, with the researchers analyzing OS, objective response rate, progression-free survival, and safety.  

Patients receiving inavolisib had a significantly higher OS compared with the placebo group, with the inavolisib group having a median OS of 34 months compared with 27 months in the placebo group. Patients receiving inavolisib had a higher probability of survival compared with the placebo group at 6 months, 12 months, 18 months, 24 months, and 30 months.  

There was also a significantly higher objective response rate in the inavolisib group compared with the placebo group. Patients had a longer median time to chemotherapy in the inavolisib group compared with the placebo group. After the final analysis, the median progression-free survival was 17.2 months for the inavolisib group and 7.3 months for the placebo group. 

The researchers found that grade 3-4 adverse events occurred in 90.7% of patients in the inavolisib group and 84.7% of patients in the placebo group but noted no additional grade 5 adverse events in the final analysis. 

“The INAVO120 trial has identified a targeted treatment regimen that meaningfully improves survival in patients with untreated PIK3CA-mutated HR+ metastatic breast cancer — a big step forward for these patients. This study illustrates the importance of genomic testing at the time of diagnosis of HR+ metastatic breast cancer, so that patients with PIK3CA mutations who qualify for this approach can be readily identified.” 

- Jane Lowe Meisel, MD, of the Winship Cancer Institute of Emory University, who was not involved with the study, said in a press release. 

-- 

References: 

https://meetings.asco.org/abstracts-presentations/244382  

https://clinicaltrials.gov/study/NCT04191499  

https://www.asco.org/about-asco/press-center/news-releases/treatment-combination-inavolisib-extends-survival-delays-chemotherapy-some-patients-advanced-breast-cancer  

Disclosures: Authors declared financial ties to drugmakers. See full study for details. This study was supported by F. Hoffmann-La Roche and the Memorial Sloan Kettering Cancer Center. 

Photo Credit: Getty Images 

By Jeff Craven