ICR supports NICE's approval of capivasertib for advanced breast cancer

The Institute of Cancer Research in London has expressed strong support for the recent approval of a targeted breast cancer treatment, combining capivasertib with fulvestrant, by the National Institute for Health and Care Excellence (NICE). This new therapeutic option is set to benefit approximately 1,100 patients annually in England and Wales who have the most prevalent type of advanced breast cancer, characterized by hormone receptor (HR) positive and human epidermal growth factor receptor 2 (HER-2) negative profiles. These are cases where the cancer has either progressed or spread following previous treatment.

Capivasertib specifically targets tumors with alterations in the PIK3CA, AKT1, or PTEN genes, mutations present in about half of the patients with this breast cancer subtype. This treatment, developed through a collaboration between AstraZeneca and Astex Pharmaceuticals, with contributions from The Institute of Cancer Research and Cancer Research Technology Limited, has the potential to benefit up to 3,000 patients annually. It was approved by the Medicines & Healthcare products Regulatory Agency (MHRA) in July 2024.

Known by the trade name Truqap, capivasertib is a pioneering drug that inhibits the activity of AKT, a protein molecule that promotes cancer growth. The drug’s development was a significant focus of the Breast Cancer Now Toby Robins Research Centre, where Professor Nicholas Turner of the Institute of Cancer Research and The Royal Marsden NHS Foundation Trust led the international phase III CAPItello-291 trial. Sponsored and funded by AstraZeneca, the trial demonstrated that capivasertib, when combined with hormone therapy, more than doubled the period before cancer progression from 3.1 months to 7.3 months, compared to hormone therapy alone.

Traditionally, patients with this advanced stage of HR-positive HER-2 negative breast cancer in the UK had limited treatment options. They could continue with fulvestrant hormone therapy, which is often ineffective when used in isolation, or undergo chemotherapy, which is associated with severe side effects. The introduction of capivasertib offers a promising alternative, as it has shown significant efficacy in extending the time before cancer progression while minimizing side effects.

The journey to capivasertib’s development was rooted in fundamental research conducted at The Institute of Cancer Research, focused on understanding AKT protein regulation. Recognizing AKT as a crucial target for anti-cancer treatment due to its role in cancer cell growth and survival, researchers published the 3D structure of the protein in 2002. Collaborative efforts with Astex Pharmaceuticals, supported by Cancer Research UK, led to the design of small-molecule inhibitors targeting AKT.

Following the promising early-phase trials led by The Institute of Cancer Research and The Royal Marsden, phase II studies were conducted in the UK through collaboration with the UK Cancer Research Network. These trials utilized biomarkers developed at The Institute of Cancer Research to validate the effectiveness of capivasertib in inhibiting the AKT protein.

The drug has received praise from patients like Elen from Anglesey, an NHS nurse diagnosed with lobular breast cancer in 2008. After conventional treatments and a period of remission, her cancer returned, affecting her bones, stomach, and bowel. Since starting capivasertib in February, Elen reports significant improvements, with no side effects and a dramatic reduction in cancer markers. She describes the treatment as groundbreaking and a game-changer, providing her with renewed hope for the future.

Professor Nicholas Turner emphasizes the importance of testing breast cancer patients for specific biomarkers to identify those who could benefit from the capivasertib combination. Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, hails the approval as a major victory that enhances treatment options for patients with advanced breast cancer, marking a significant milestone for British scientific innovation and collaboration.