Median progression-free survival of 15.0 months against 7.3 months on placebo: that gap in the INAVO120 trial is what carried Genentech’s inavolisib to US approval. The FDA announced the decision on October 10, 2024. The drug will be sold as Itovebi.
It is cleared for adults with locally advanced or metastatic breast cancer that is hormone receptor (HR)-positive, HER2-negative, PIK3CA-mutated and resistant to endocrine therapy. Doctors can start it after a recurrence, whether the relapse came during adjuvant endocrine therapy or after it ended. It is given together with palbociclib and fulvestrant.
What the trial showed
INAVO120 was a Phase 3 study, randomized, double-blind and placebo-controlled, run at multiple centers. It enrolled 325 patients whose disease progressed during or within 12 months of finishing adjuvant therapy. None had received earlier systemic therapy for the advanced cancer.
One group took inavolisib 9 mg by mouth daily. The other took a placebo on the same schedule. Everyone also received palbociclib 125 mg daily for three weeks followed by a week off, plus fulvestrant 500 mg on days 1 and 15 of the first cycle and then every 28 days. Treatment stopped on disease progression or unacceptable toxicity.
Progression-free survival was the main measure. The inavolisib arm reached a median of 15.0 months (95% CI, 11.3-20.5), while the placebo arm managed 7.3 months (95% CI, 5.6-9.3). The hazard ratio was 0.43 (95% CI, 0.32-0.59).
The objective response rate was 58% (95% CI, 50%-66%) with inavolisib and 25% (95% CI, 19%-32%) with placebo. Responses also lasted longer: a median of 18.4 months (95% CI, 10.4-22.2) for the inavolisib group, versus 9.6 months (95% CI, 7.4-16.6) for the comparison arm.
Side effects
At least 20% of patients reported each of a long list of adverse reactions. Lab findings included decreased neutrophils, increased fasting glucose, decreased hemoglobin, decreased lymphocytes and decreased platelets. Patients also reported diarrhea, fatigue, stomatitis, nausea, rash, decreased appetite, headache and COVID-19 infection.
Regulatory path and company view
The FDA had given the drug Priority Review and Breakthrough Therapy Designation in May 2024. Inavolisib is still being studied in other Phase 3 trials in PIK3CA-mutated locally advanced or metastatic breast cancer.
Levi Garraway, MD, PhD, Genentech’s chief medical officer and head of Global Product Development, put the company’s case in a press release. “Despite the high prevalence of PIK3CA mutations in this setting, treatment options have thus far remained limited, which makes today’s approval all the more significant,” he said. He described the regimen as “an important new first-line option” for people with HR-positive breast cancer carrying the mutation.
