Inavolisib plus palbociclib and endocrine therapy in ER+/HER2- advanced breast cancer

Inavolisib, a novel potent and selective small-molecule inhibitor of p110α that promotes the degradation of mutated p110α, has a manageable safety profile, good tolerability and a promising preliminar antitumor activity in PIK3CA-mutated, ER+/HER2- locally advanced/metastatic breast cancer patients when added to palbociclib and endocrine therapy, as shown by a study recently published on The Journal of Clinical Oncology.

A phase I/Ib trial involved 55 patients to investigate safety, tolerability, pharmacokinetics and preliminary antitumor activity of inavolisib in association with palbociclib and letrozole or palbociclib and fulvestrant. Data showed that grade 3 or more treatment-related adverse events were present in more than 85% of patients, with discontinuation due to adverse effects ranging from 6.1% (letrozole treated group) to 10% (fulvestrant treated group); no drug–drug interactions were reported. Confirmed objective response rates were 52.0% and 40.0% in patients with measurable disease, and median progression-free survival was 23.3 and 35.0 months in the Inavo + Palbo + Letro and Inavo + Palbo + Fulv arms, respectively; data also confirmed an effect of the combination on pathophysiologic markers of response too. As authors say, «These data demonstrate the synergistic effect of targeting the estrogen receptor, CDK4/6, and PI3K pathways in PIK3CA-mutated, HR+/HER2–  locally advanced/metastatic breast cancers, thus supporting the further evaluation of inavolisib and palbociclib plus fulvestrant in the phase III INAVO120 study, an ongoing phase III trial that evaluates the combination of inavolisib, palbociclib, and fulvestrant in patients with PIK3CA-mutated, HR+/HER2–, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received previous systemic therapy for metastatic disease. INAVO120 demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, and manageable safety profile and tolerability».