First-in-class capivasertib approved by MHRA and EC for advanced breast cancer

19th July 2024

The AKT inhibitor capivasertib (brand name Truqap) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) for treating eligible patients with advanced breast cancer.

Capivasertib is indicated in combination with the hormone therapy fulvestrant for treating advanced hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced breast cancer with specific biomarker alterations (PIK3CA, AKT1 or PTEN) following recurrence or progression on or after an endocrine-based regimen.

This follows the marketing authorisation of capivasertib by the European Commission (EC) in June 2024 for the same indication.

The first-in-class drug is taken orally at a starting dose of 400 mg twice a day for four days followed by three days of rest, then repeated.

Safety and efficacy of capivasertib

The MHRA and EC approvals were based on the results of the phase 3, randomised, double-blind CAPItello-291 trial, which included 708 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer. Of these, 289 patients (40.8%) had AKT pathway alterations.

Patients were randomised to receive either capivasertib or a placebo, both in combination with fulvestrant. The dual primary endpoint was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway–altered (PIK3CA, AKT1, or PTEN) tumours.

In the overall population, the median progression-free survival was 7.2 months in the capivasertib–fulvestrant group, as compared with 3.6 months in the placebo–fulvestrant group (HR 0.60; 95% CI, 0.51 to 0.71; P<0.001).

In the AKT pathway–altered population, the median progression-free survival was 7.3 months in the capivasertib–fulvestrant group, as compared with 3.1 months in the placebo–fulvestrant group (HR 0.50; 95% CI, 0.38 to 0.65; P<0.001).

Potential side effects of capivasertib included high blood sugar, diarrhoea, rash and other skin drug reactions, urinary tract infection, low level of haemoglobin in blood, loss of appetite, nausea, vomiting, mouth sores or ulcers with gum inflammation, itching, and tiredness.

The most frequent adverse events of grade 3 or higher in patients receiving capivasertib–fulvestrant were rash (12.1% vs in 0.3% of those receiving placebo–fulvestrant) and diarrhoea (9.3% vs 0.3%).

Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo.

‘Exciting new targeted treatment’

Professor Nicholas Turner, professor of molecular oncology at The Institute of Cancer Research, London, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, who led the CAPItello-291 trial, said the MHRA approval is ‘wonderful development in the treatment of the most common type of advanced breast cancer’.

He added: ‘Around half of patients with this kind of breast cancer have mutations in one or more of the genes PIK3CA, AKT1 or PTEN, and for these patients, capivasertib provides an exciting, new targeted treatment which can keep their cancer from progressing for longer.

‘We hope NICE will recommend the use of capivasertib in combination with fulvestrant for patients on the NHS.’

Speaking about the EC marketing authorisation of this AKT inhibitor, Dr Mafalda Oliveira, senior clinical investigator of the Vall d’Hebron Institute of Oncology’s Breast Cancer Group in Barcelona, Spain, said: ‘Patients with advanced [HR]-positive breast cancer typically experience tumour progression or resistance with widely used endocrine-based treatment regimens, and there is an urgent need to provide them more time with their disease under control.

‘[This] approval is welcome news for approximately half of [HR]-positive breast cancer patients in Europe who have tumours with these biomarkers, and it is important for clinicians to test and identify eligible patients who may be able to benefit from this combination.’

Talazoparib recommended by NICE for advanced breast cancer after initial rejection

23rd January 2024

The poly ADP-ribose polymerase (PARP) inhibitor talazoparib (brand name Talzenna) has been recommended by the National Institute for Health and Care Excellence (NICE) to treat a type of locally advanced or metastatic breast cancer.

The final draft guidance from NICE recommends talazoparib for the treatment of adults with BRCA 1 or 2 mutated HER2-negative locally advanced or metastatic breast cancer after prior chemotherapy.

Evidence from a clinical trial showed that talazoparib increases how long people live without their cancer getting worse compared with chemotherapy. The trial did not show any difference in how long people live.

NICE originally rejected talazoparib for breast cancer in July 2023, but reversed the decision after the manufacturer Pfizer offered an increased – and confidential – discount to the drug’s price.

The draft guidance states: ‘When considering the condition’s severity and its effect on quality and length of life, the most likely cost-effectiveness estimates for talazoparib are within the range that NICE considers an acceptable use of NHS resources. So talazoparib is recommended.’

The final guidance is expected to be published on 21 February 2024, and this will make talazoparib the first targeted treatment for this type of advanced breast cancer available in the NHS. This treatment would be instead of chemotherapy.

Current treatments include chemotherapy (mainly taxanes) and best supportive care, and alternative treatment options have been limited.

Helen Knight, director of medicines evaluation at NICE, said: ‘[This] announcement addresses a significant need by giving people with these types of cancer access to an additional treatment. And because talazoparib is taken as a once-daily tablet it means it’s much more convenient for people who would otherwise need to go into hospital for intravenous chemotherapy.

‘Although some uncertainty in the clinical evidence remains, when considering the impact of advanced breast cancer and its effect on quality and length of life, the improved discount from the company means we can now recommend talazoparib for use in the NHS.’

Earlier in January, talazoparib was approved by the European Commission in combination with the androgen receptor blocker enzalutamide in eligible patients with prostate cancer.

EMA recommends approval of olaparib for treatment of high-risk, early breast cancer

27th June 2022

The EMA has recommended approval of olaparib in high-risk, early-stage breast cancer with inherited faults in BRCA1 or BRCA2 genes

The Institute of Cancer Research, London, strongly welcomes the news that olaparib has been recommended by the European Medicines Agency (EMA) to treat people with high-risk, early-stage breast cancer who have inherited faults in their BRCA1 or BRCA2 genes.

The next step is for the European Commission to grant marketing authorisation, a process likely to take place in the next few months. Once this licensing step is completed, people in the EU with early breast cancer and BRCA mutations, who have already been treated with chemotherapy, either before or after surgery, will be a step closer to accessing olaparib, on its own or in combination with hormone therapy.

The recommendation follows the latest findings from the Phase III OlympiA trial, which showed that adding the targeted drug olaparib to standard treatment cuts the risk of women dying by 32 per cent – resulting in more women remaining cancer free and becoming breast cancer survivors.

Professor Andrew Tutt at The Institute of Cancer Research (ICR) and King’s College London is Chair of the Steering Committee for the OlympiA trial, which was coordinated by the Breast International Group (BIG). Professor Tutt was also involved in early laboratory research at the Breast Cancer Now Toby Robins Research Centre at the ICR on PARP inhibitors such as olaparib, and their subsequent clinical development.

Olaparib, which is taken orally, was recently approved in the US for the same group of people – those with high-risk, early-stage breast cancer who have inherited faults in their BRCA1 or BRCA2 genes.

Olaparib is also approved for use in the US, EU and UK for the treatment of patients with advanced breast cancer who have inherited faults in their BRCA1 or BRCA2 genes and were previously treated with chemotherapy.

OlympiA Steering Committee Chair Professor Andrew Tutt, Professor of Oncology at The Institute of Cancer Research, London, and King’s College London said:

“Olaparib is the first PARP inhibitor to increase the chances of curing people with early-stage breast cancer after initial treatment.

“Most breast cancers identified at an early stage are likely to be cured, but even with the best standard treatments, there is a high-risk group of women who are still likely to see their cancer return. Olaparib is a targeted treatment option that can keep these women with inherited high-risk breast cancer due to BRCA1/2 gene faults free of disease.

“Today’s recommendation brings olaparib a step closer to approval in Europe for people with high-risk, early-stage breast cancer. The next steps are for the MHRA to make a recommendation in the UK, and for NICE to carry out its appraisal, so that NHS patients in England can access olaparib without delay. We hope these processes can proceed as quickly as possible given the EMA recommendation.”

Professor Kristian Helin, Chief Executive of The Institute of Cancer Research, London, said:

“Science carried out at the ICR underpinned the development of PARP inhibitors like olaparib. Initially shown to benefit those with advanced breast, ovarian and prostate cancers, olaparib could now be used to reduce the risk of disease returning in early-stage breast cancer.

“It is tremendously exciting that the OlympiA trial shows olaparib could be successfully used to treat women with early-stage breast cancer and inherited BRCA mutations to improve their survival outcomes.

“BRCA1 and BRCA2 mutations are the most common cause of hereditary breast cancer – around 5 to 10 percent of breast cancers are the result of mutations in these genes.

This means that thousands of people with early breast cancer could benefit from being treated with olaparib, and I look forward to seeing BRCA1 and BRCA2 testing used more widely for those diagnosed with early-stage breast cancer, so that we can identify those likely to benefit from this game-changing targeted treatment.”