INAVO 120 study

At the 2025 ASCO Annual Meeting, updated results from the phase 3 INAVO120 trial were presented by Prof Nicholas Turner, with expert insights from Prof François Duhoux and Dr Laure-Anne Teuwen. This randomised, double-blind, placebo-controlled study evaluated the addition of inavolisib to fulvestrant and palbociclib in patients with HR+, HER2-negative MBC with poor prognosis, defined as progression during or within 12 months after adjuvant endocrine therapy. With a median follow-up of nearly three years, inavolisib significantly improved PFS to 17.2 months versus 7.3 months in the placebo group, a nearly 10-month difference. This translated into a median OS increase from 27.0 to 34.0 months (HR 0.67). Time to chemotherapy was also notably prolonged by approximately two years in the inavolisib arm, an important quality-of-life benefit in this setting. 

Prof Duhoux and Dr Teuwen highlighted the durability of the PFS benefit and the clinical value of delaying chemotherapy in patients at high risk of rapid progression. While hyperglycemia was the most common adverse event with inavolisib (63.4% vs. 13.5%), discontinuation rates remained low at 6.8%, indicating acceptable tolerability. 

The experts noted that fulvestrant plus palbociclib is not the preferred first-line standard in current practice, where combinations with ribociclib or abemaciclib have demonstrated stronger OS data. However, palbociclib’s favorable safety profile made it a suitable partner for inavolisib in this study. Despite this limitation, the magnitude of benefit with inavolisib was considered clinically meaningful. They also discussed the lack of a crossover design and limited subsequent PI3K inhibitor use in the placebo group (10% in second line, 5% in third), reflecting restricted access in clinical practice. Given the aggressive nature of the disease, they emphasised that delaying the use of effective targeted agents is no longer appropriate for many patients.