Positive results with inavosilib added to palbociclib and fulvestrant in advanced breast cancer

Inavosilib added to palbociclib and fulvestrant led to a significantly longer progression-free survival in patients with PIK3CA-mutated HR+/HER2- locally advanced or metastatic breast cancer, as shown by a new analysis of the INAVO120 trial recently published on The New England Journal of Medicine.

Inavolisib is a novel potent and selective small-molecule inhibitor of p110α that promotes the degradation of mutated p110α. In the phase 3, double-blind randomized INAVO 120 trial, first-line inavosilib (9 mg once daily, orally) plus palbociclib–fulvestrant was compared with placebo plus palbociclib–fulvestrant in a total of 325 patients with PIK3CA-mutated HR+/HER2- locally advanced or metastatic breast cancer. After a median follow-up of more than 21 months in both groups, the median progression-free survival was 15 months in the inavolisib group and 7.3 months in the placebo group, whereas an objective response occurred in 85.4% and 25% of patients, respectively. Inavosilib group showed also a greater incidence of toxic effects, but the percentage of patients who discontinued any trial agent because of adverse events was low. All the combination treatment were used at full doses and as authors say «The substantial clinical benefit observed in our trial can be attributed to the simultaneous blockade of the three critical signaling pathways that drive PIK3CA-mutated, HR+, HER2- locally advanced or metastatic breast cancer (the PI3K, estrogen receptor, and CDK4/6 pathways), which delayed and prevented the emergence of treatment resistance directed mainly by cross-talk among these pathways. Moreover, the clinical benefit of the inavolisib regimen occurred early after the start of treatment and was durable. Inavolisib plus palbociclib–fulvestrant may thus represent a new treatment option for these patients».

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