Targeted breast cancer drug extends lives of patients in Phase III trial

Patient using a mammography machine

A new type of targeted medicine has shown ‘remarkable’ benefits for patients with advanced breast cancer in a major Phase III clinical trial. 

The drug capivasertib combined with hormone therapy doubled the time it took for cancer to progress in people with advanced forms of the most common type of breast cancer. 

The findings establish capivasertib as a potential new treatment for people with oestrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer. 

Capivasertib is a potential first-in-class drug that blocks activity of the cancer-driving protein molecule AKT. It was discovered by pharmaceutical company AstraZeneca following a programme of drug discovery research at The Institute of Cancer Research, London.  

The drug was found to be effective across all patients treated in the trial, including a group who had tumours with mutations in the AKT signalling pathway. 

Professor Kristian Helin, Chief Executive at The Institute of Cancer Research, London, said: “This is a landmark moment for the treatment of advanced forms of the most common type of breast cancer. It’s incredibly exciting to see a drug that was discovered following research conducted at the ICR now show remarkable benefits for patients in a phase III trial. Capivasertib could offer a completely new treatment option for these patients. 

“This is a major success story for UK science – the discovery and development of capivasertib showcases the benefits of collaboration between academia, charities and industry to bring game-changing new treatments to people with cancer as quickly as possible.” 

The CAPItello-291 trial

The CAPItello-291 trial enrolled 708 women and men with an advanced form of ER-positive, HER-2 low or negative locally advanced or metastatic breast cancer. 

Participants on the trial had seen their cancer recur or progress on standard hormone treatments, and the majority had also previously been treated with CDK4/6 inhibitors – drugs that block cancer cells from multiplying. 

In the trial, adding capivasertib to fulvestrant hormone therapy doubled the median time to disease progression, from 3.6 months to 7.2 months. The treatment shrank tumours in 22% of patients, compared with 12% who received fulvestrant hormone treatment plus a placebo. 

Genetic alterations of the AKT pathway

The targeted drug was more effective for patients whose cancers had alterations to the AKT signaling pathway. Genetic alterations to the AKT pathway can drive both cancer’s development and treatment resistance. 

Genetic alterations of the AKT pathway were present for 41% of patients on the trial. In this group treated with capivasertib and hormone therapy, it took an average of 7.3 months for the cancer to worsen compared with 3.1 months for those who received hormone therapy alone. Some 29% of patients with AKT pathway alterations who received capivasertib with hormone therapy saw their tumours shrink following treatment, compared with only 9.7% who received a placebo and hormone therapy. 

Trial leader Professor Nick Turner, Professor of Molecular Oncology at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said: “This is a fantastic finding for patients with breast cancer. Even with the best current treatments, people with this type of advanced breast cancer will eventually see their cancer stop responding to treatment, and it will progress. We’re delighted that this potential first-in-class drug combined with hormone therapy can slow the progression of these advanced cancers, and in almost a third of cases can shrink tumours. 

“We are hopeful that capivasertib combined with hormone therapy will now become a new treatment option for patients whose cancer has progressed on hormone therapy plus a CDK4/6 inhibitor. We believe this new treatment could allow more women and men to live well and live longer with breast cancer.” 



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