Shutterstock.com
A phase III trial of a new drug for the treatment of advanced breast cancer has shown that adding it to hormone therapy can lengthen time to disease progression and increase the chance of a tumour shrinking.
Researchers at The Royal Marsden NHS Foundation Trust and the Institute of Cancer Research (ICR) enrolled 708 people in a randomised controlled trial of capivasertib — an inhibitor of the cancer-driving protein AKT, developed by AstraZeneca and the ICR in London — in combination with hormone treatment.
Participants had oestrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer, which was locally advanced or metastatic, despite previous treatment with standard hormone treatment.
Most participants (69%) had also been treated previously with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. In clinical practice, people in this situation usually continue to receive the hormone treatment fulvestrant, although this is often not effective. The only other option is chemotherapy.
As part of the trial, researchers randomly assigned participants to one of two groups, with one group receiving fulvestrant and capivasertib, and another receiving fulvestrant and a placebo.
Capivasertib, in combination with fulvestrant hormone therapy, was found to increase progression-free survival from 3.6 months to 7.2 months, compared with hormone therapy alone. For 23% of patients who received combination therapy, tumours shrank, compared with 12% taking hormone therapy alone.
The results were similar for people with and without AKT pathway-altered tumours, assessed by gene sequencing, the researchers found.
However, 13% of participants stopped taking capivasertib because of adverse events; the most common being diarrhoea, rash and nausea. Researchers described the safety profile as “generally manageable and consistent with prior data”.
“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,” said Nick Turner, professor of molecular oncology at the ICR in London and consultant medical oncologist at The Royal Marsden NHS Foundation Trust.
“We’re delighted that this potential first-in-class drug combined with hormone therapy can slow the progression of these advanced cancers.”
Turner said he hoped it would now become a new treatment option for the two thirds of people with advanced breast cancer who have ER+/HER2- disease.
Dharmisha Chauhan, specialist oncology pharmacist at the Royal Marsden NHS Foundation Trust, said the positive findings were “another step” in precision therapy.
“This study highlights the importance of understanding how tumours in breast cancer signalling pathways allow cancer cells to grow again or lead to treatment resistance after first- or second-line treatment approaches,” she said.
“Understanding how cancer cells can circumnavigate pathways leading to treatment resistance is incredibly important to understand how patients’ outcomes can be significantly improved.
“The study indicates the importance of tumour sequencing across a cancer signalling pathway to find the right drug for the right patient.”
Chauhan added that the targeted treatment approach would be “practice changing” once the required approvals were obtained.
The study was presented on 8 December 2022 at the San Antonio Breast Cancer Symposium. It was funded by AstraZeneca.
