Drug Combination Increases Survival in Patients With Advanced Breast Cancer

Mutations in the PIK3CA gene are a key driver of breast cancer and are present in 35-40% of hormone receptor–positive breast cancers. A recently completed phase 3 clinical trial, conducted by researchers at Mass General Brigham and collaborators, shows that combining inavolisib with palbociclib and fulvestrant improves overall survival for patients with advanced PIK3CA-mutated breast cancer. Results of the study are published in The New England Journal of Medicine and presented at the American Society of Clinical Oncology (ASCO) annual meeting.

“These results support the efficacy of this precision oncology approach, particularly in patients with disease characteristics indicating a poor prognosis, for whom early and rapid disease control is crucial for attaining better long-term outcomes,” said co-senior author Dejan Juric, MD, director of the Termeer Center for Targeted Therapies and the Investigational Cancer Therapeutics Program at the Mass General Cancer Center, a member of the Mass General Brigham healthcare system. The three-drug treatment regimen was FDA approved last October, based on the progression-free survival results from the trial. “This report provides further evidence of the treatment’s long-term safety and effectiveness, and underscores the importance of PIK3CA mutation testing in patients with hormone receptor-positive advanced breast cancer."

The phase 3 double-blind, randomized trial involved 325 patients from 28 countries who were randomly assigned to receive either the standard treatment (palbociclib and fulvestrant) plus inavolisib, or the standard treatment plus a placebo. Patients who received inavolisib had a median overall survival of 34 months compared to 27 months for the placebo group. Inavolisib treatment was associated with longer periods without cancer progression (17.2 months vs 7.3 months in the placebo group) and higher rates of tumor shrinkage (62.7% vs 28.0%). Patients who received inavolisib treatment were also less likely to need chemotherapy or other supplementary cancer therapy.

However, inavolisib treatment was associated with higher rates of side effects, including high blood sugar, mouth sores, diarrhea and eye problems. Overall, serious adverse events were observed in 27.3% of patients who received inavolisib compared to 13.5% of patients in the placebo group. Adverse events led to the discontinuation of inavolisib in 6.8% of patients, compared to 0.6% for placebo.

The team plans to further analyze the treatment’s effectiveness and safety in underrepresented groups, including patients over the age of 65.

Reference: Jhaveri Komal L., Im Seock-Ah, Saura Cristina, et al. Overall survival with inavolisib in PIK3CA-mutated advanced breast cancer. NEJM. 2025. doi: 10.1056/NEJMoa2501796

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