The UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved inavolisib (Itovebi, Roche Products Limited) for adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer.

The targeted therapy is authorised for use with palbociclib and fulvestrant in patients whose disease carries the phosphatidylinositol-3-kinase catalytic subunit alpha gene (PIK3CA) mutation and has relapsed or progressed after endocrine therapy. The MHRA said the decision gives clinicians a new first-line option for a biomarker-defined population with substantial unmet need.

Julian Beach, interim executive director of healthcare quality and access at the MHRA, noted that the drug “can help delay the progression of the disease, giving patients more time with effective treatment.”

How Inavolisib Works

Inavolisib is a highly potent and selective inhibitor of the alpha isoform of the p110 catalytic subunit of the phosphatidylinositol 3-kinase complex. It also promotes degradation of the mutated p110 alpha protein.

The medicine is supplied as a film-coated tablet taken orally.

Clinical Evidence

Approval is supported by data from the phase 3 INAVO120 trial, which compared first-line inavolisib (9 mg once daily) plus palbociclib and fulvestrant against placebo plus the same combination in patients with PIK3CA-mutated disease. 

The trial enrolled 325 patients with HR+/HER2- locally advanced or metastatic breast cancer that relapsed during or within 12 months after completion of adjuvant endocrine therapy.

Median progression-free survival reached 15.0 months in the inavolisib group compared with 7.3 months in the placebo group, representing a 57% reduction in disease progression or risk for death. The objective response rate was 58.4% with inavolisib compared with 25.0% with placebo.

Safety and Monitoring

Common adverse effects include hyperglycaemia, stomatitis, diarrhoea, fatigue, anaemia, nausea, decreased appetite, rash, headache, weight loss, vomiting, and urinary tract infections. 

Laboratory abnormalities include decreased white blood cell, red blood cell, and platelet counts, along with reduced blood levels of calcium, potassium, sodium, and magnesium. Elevated creatinine and alanine aminotransferase levels were also observed. COVID-19 occurred in some patients. Additionally, the treatment may affect fertility in males and in females who are able to become pregnant. 

Detailed prescribing information will be available in the Summary of Product Characteristics and Patient Information Leaflets, which will be published on the MHRA website within 7 days. 

The MHRA encouraged clinicians and patients to report any suspected adverse reactions through the Yellow Card scheme, noting that the medicine remains under additional safety monitoring.