Inavolisib: The first FDA-approved treatment for use in a triplet combination for metastatic breast cancer

Inavolisib, in combination with palbociclib and fulvestrant, met its primary endpoint of progression-free survival (PFS) in patients with PIK3CA-mutated, HR-positive/HER2-negative metastatic breast cancer (mBC) in the INAVO120 trial. The FDA has determined that the benefit-risk assessment is favourable for using this triplet combination in this specific patient population.

The phase 3 INAVO120 trial (NCT04191499) enrolled patients with PIK3CA-mutated, HR-positive/HER2-negative mBC with endocrine resistance, a population associated with poor prognosis [1,2]. Dr Suparna Wedam (CDER, U.S. Food and Drug Administration, MD, USA) discussed the positive outcome of this trial that led to the FDA approval of inavolisib in this patient group [3]. The participants were randomised in a 1:1 ratio to receive either inavolisib, a PI3Kα inhibitor (n=161), or placebo (n=164), in combination with palbociclib and fulvestrant.

The trial achieved its primary endpoint of significantly longer PFS in the inavolisib group compared to the placebo group, with a median PFS of 15 months versus 7.3 months (HR 0.43; 95% CI 0.32–0.59; P<0.001). PFS results evaluated by blinded independent committee review supported the primary endpoint. The interim OS results were immature, but the final OS results will be submitted in due course. Increased adverse event rates were observed in the inavolisib group, particularly for hyperglycaemia, diarrhoea, and stomatitis. These clinically observed adverse events were supported by the patient-reported outcomes. “The increased toxicity seen with this triplet combination really does present an opportunity for future dose optimisation,” Dr Wedam commented.

Dr Wedam concluded that “inavolisib is the first FDA-approved treatment to be used in a triplet combination specifically for the first-line treatment of patients with PIK3CA-mutated locally advanced or metastatic HR-positive/HER2-negative breast cancer considered to be endocrine resistant.” The results were positively received, with one of the panel members adding that they would prescribe this treatment in the patient who recurs during or shortly after adjuvant endocrine therapy with a PIK3CA mutation, high disease volume, and visceral metastases.

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   1. Turner NC, et al. N Engl J Med. 2024;391(17):1584-1596.
   2. Mosele F, et al. Ann Oncol. 2020;31(3):377-386.
   3. Wedam SB, et al. New Drug Approvals for Breast Cancer. Inavolisib. FDA Special Session, SABCS 2024, 10–13 December, San Antonio, TX, USA.

Medical writing support was provided by Kulsoom Abdul
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Posted on 16 December 202416 December 2024