Treatment with the PI3K inhibitor inavolisib in combination with palbociclib and fulvestrant produced substantial clinical benefits in Asian patients with PIK3CA-mutated, hormone receptor–positive (HR-positive), HER2-negative, endocrine-resistant advanced breast cancer, according to a subgroup analysis of the phase III INAVO120 trial. The research was highlighted in a media briefing ahead of the 2026 ASCO Breakthrough Meeting, taking place June 25 to June 27 in Singapore.
The regimen demonstrated improvements across multiple efficacy endpoints, including progression-free survival, overall response rate, and overall survival, while maintaining a manageable safety profile consistent with that observed in the overall study population.
Study Details
The subgroup analysis focused on patients enrolled in Asia as part of the global phase III INAVO120 study. The trial enrolled 325 patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer that had become resistant to endocrine therapy. Among them, 120 patients were treated at centers in Asia.
Participants were randomly assigned to receive either inavolisib or placebo, each in combination with the CDK4/6 inhibitor palbociclib and the estrogen receptor antagonist fulvestrant. Of the Asian cohort, 58 patients received the inavolisib-containing regimen and 62 received placebo plus standard therapy. Treatment continued until disease progression, unacceptable toxicity, or death.
According to lead investigator Yoon Sim Yap, MBBS, FRACP, PhD, of the National Cancer Centre Singapore, the analysis addresses an important unmet need for effective targeted therapies in Asian patients with endocrine-resistant disease, a population that often experiences rapid disease progression.
Key Results
Results in the Asian subgroup closely mirrored and in some cases numerically exceeded those observed in the overall INAVO120 population. The objective response rate was 60.3% among patients receiving inavolisib compared with 27.4% in the placebo group. Responses were also more durable, with a median duration of response of 18.8 months vs 10.7 months, respectively.
The median progression-free survival was 14.8 months with the addition of inavolisib compared with 6.8 months for patients receiving placebo. Investigators also evaluated time to chemotherapy or death, a clinically meaningful measure of disease control. Patients treated with inavolisib remained free from chemotherapy longer, with a median time to chemotherapy or death of 19.2 months compared with 10.6 months in the control arm.
Median overall survival reached 32.7 months in the inavolisib group vs 27.0 months among patients who received placebo. Safety findings were consistent with those reported in the broader INAVO120 study, with no new adverse events identified in Asian patients. The most common serious adverse events associated with inavolisib were fever and febrile neutropenia. Notably, treatment discontinuations due to adverse effects were infrequent and appeared lower than those reported in the overall trial population.
Breast cancer remains the most commonly diagnosed cancer worldwide, and approximately 70% of patients have HR-positive, HER2-negative disease. About 40% of these tumors harbor PIK3CA mutations, making PI3K inhibition an important therapeutic strategy. The current findings provide additional evidence that the benefits of inavolisib extend across diverse patient populations and support its role as a standard treatment option for patients with endocrine-resistant, PIK3CA-mutated advanced breast cancer.
DISCLOSURE: For full disclosures of the study authors, visit coi.asco.org.
