Multinational phase 3 trial of inavolisib-based therapy for PIK3CA-mutated advanced breast cancer

Inavolisib is a selective inhibitor of the alpha isoform of the p110 catalytic subunit of the phosphatidylinositol 3-kinase complex. The multinational phase 3 INOVA120 trial evaluated inavolisib plus palbociclib-fulvestrant (inavolisib group) versus placebo plus palbociclib-fulvestrant (placebo group) for PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer (aBC). The median progression-free survival was 15.0 months in the inavolisib group versus 7.3 months in the placebogroup (HR 0.43; p<0.001); an objective response occurred in 58.4% versus 25.0%. The incidence of grade 3 or 4 neutropenia was 80.2% in the inavolisib group and 78.4% in the placebo group; the incidence of grade 3 or 4 hyperglycemia was 5.6% and 0%, respectively; the incidence of grade 3 or 4 stomatitis or mucosal inflammation was 5.6% and 0%; and the incidence of grade 3 or 4 diarrhea was 3.7% and 0%. Discontinuation of any trial agent because of adverse events occurred in 6.8% of the patients in the inavolisib group and 0.6% of those in the placebo group. The authors conclude that in patients with PIK3CA-mutated, HR-positive, HER2-negative aBC, inavolisib plus palbociclib-fulvestrant led to significantly longer progression-free survival than placebo plus palbociclib-fulvestrant, with a greater incidence of toxic effects. The percentage of patients discontinuing due to adverse events was low.