Inavolisib in PIK3CA-Mutated Advanced Breast Cancer

For patients with ER+/HER2− metastatic breast cancer, standard first line therapy is usually an endocrine agent plus an aromatase inhibitor. The subset of patients with tumors harboring a PIK3CA mutation, particularly patients with rapid progression following adjuvant therapy, have a shorter progression-free interval than those with PIK3CA wild-type tumors.

In the industry-funded, phase 3 INAVO120 trial, researchers enrolled 325 adults with locally advanced or metastatic PIK3CA-mutated, hormone receptor–positive, HER2-negative, endocrine-resistant breast cancer who had disease recurrence or progression after completing adjuvant endocrine therapy. Patients were randomized to receive either the selective PI3Kα inhibitor inavolisib (9 mg orally once daily) or placebo; all participants received palbociclib and fulvestrant.

The inavolisib group had a median overall survival of 34 months, compared with 27 months in the placebo group. Progression-free survival (PFS), which was previously reported, continued to favor the inavolisib group (median, 17 vs. 7 months for placebo). In addition, the inavolisib group had a significantly greater objective response rate than the placebo group (63% vs. 28%).

Inavolisib recipients had higher incidences of hyperglycemia, stomatitis or mucosal inflammation, diarrhea, and ocular toxicities. They were also more likely to experience serious adverse events (27% vs. 14% of placebo recipients).