What is the efficacy of Itovebi (inavolisib)-u200c inaliside?

Itovebi (inavolisib) is indicated for the combined treatment of PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Inavolisib is a highly potent and selective inhibitor of the alpha isoform of the p110 catalytic subunit of the phosphatidylinositol 3-kinase complex (encoded by PIK3CA), which also promotes the degradation of mutated p110α. Inavolisib plus palbociclib and fulvestrant has shown synergistic activity in preclinical models and promising anti-tumor activity in early-stage trials.

In a phase 3, double-blind, randomized trial, first-line inavolisib (9 mg orally once daily) plus palbociclib-fulvestrant was compared with placebo plus palbociclib< /span>-Fulvestrant treatmentPatients with PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer who relapse during or within 12 months after completion of adjuvant endocrine therapy. The primary endpoint was investigator-assessed progression-free survival.

Clinical studies showed that a total of 161 patients were assigned to the Itovebi group and 164 to the placebo group; the median follow-up times were 21.3 months and 21.5 months respectively. The median progression-free survival in the combination group was 15.0 months (95% confidence interval [CI], 11.3-2 0.5) versus 7.3 months (95% CI, 5.6-9.3) in the placebo group (hazard ratio for disease progression or death, 0.43; 95% CI, 0.32-0.59; P<0.001). 58.4% of the patients in the combination group experienced objective response, and 25.0% of the patients in the placebo group experienced objective response.

The incidence of grade 3 or 4 neutropenia was 80.2% in the Itovebi group and 78.4% in the placebo group; grade 3 or 4 hyperglycemia, 5.6% and 0%, respectively; grade 3 or 4 stomatitis or mucosal inflammation, 5.6% and 0%; and grade 3 or 4 diarrhea, 3.7% and 0%, respectively. No grade 3 or 4 rash was observed. The incidence of discontinuation of any trial drug due to adverse events was 6.8% in the enalapril group and 0.6% in the placebo group.

The study results show that in patients with PIK3CA mutation, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer, Itovebi combined withPalbociclib-Fulvestrant resulted in significantly longer progression-free survival and a higher incidence of toxicity than placebo plus palbociclib-Fulvestrant. The proportion of patients who discontinued any trial drug because of adverse events was low.