The US Food and Drug Administration (FDA) has approved Roche’s Itovebi (inavolisib) in combination with Pfizer’s Ibrance (palbociclib) and AstraZeneca’s Faslodex (fulvestrant) as the first-line treatment for certain breast cancer patients.
The combination therapy is approved for patients with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy.
Itovebi’s main competitor for this patient group is Novartis’s Piqray (alpelisib), which was approved by the FDA in 2019. Despite Piqray’s early-to-market advantage, GlobalData estimates that Itovebi’s sales will eclipse Piqray in coming years, with the former raking in over $1bn in 2030 compared to estimated sales of $480m for Piqray during the same time.
GlobalData is the parent company of Pharmaceutical Technology.
The FDA approval is based on positive data from the placebo-controlled Phase III INAVO120 trial (NCT04191499). The study evaluated the combination therapy in 325 breast cancer patients. In December 2023, Roche reported that the Itovebi combination therapy had a mean progression-free survival (PFS) of 15 months, compared to the mean PFS of 7.3 months in patients who received the placebo, Ibrance and Faslodex combination.
The company noted that whilst the overall survival data was still immature during the primary analysis, it showed a “clear positive trend” in favour of the Itovebi combination arm. Improvements in other secondary endpoints included increases in objective response rate (ORR), duration of response (DoR) and clinical benefit rate were also noted by Roche, however, the company did not provide further details.
The most common Grade 3/4 adverse effects with the Itovebi combination were haematological abnormalities, such as neutropenia, thrombocytopenia and anaemia, hyperglycaemia, and stomatitis (inflammation of the mouth and lips). The study also reported discontinuation rates of 6.8% in the Itovebi group compared to 0.6% in the placebo group.
Roche is also looking to expand the Itovebi label in breast cancer and is evaluating it as a combination treatment in other breast cancer indications. A Phase III INAVO121 trial (NCT05646862) is comparing Itovebi with Piqray when used in combination with Faslodex in HR-positive/HER2-negative breast cancer patients who have previously received post cyclin-dependent kinase 4/6 inhibitor and endocrine combination therapy.
A second Phase III INAVO122 study (NCT05894239) is evaluating Itovebi in combination with Roche’s other FDA-approved breast cancer therapy Phesgo (pertuzumab, trastuzumab, and rHuPH20) as maintenance therapy after induction therapy in patients with previously untreated HER2-positive advanced breast cancer. The trial is estimated to enrol 230 participants and compares the combination therapy with Phesgo monotherapy.
