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The final draft guidance from NICE recommends talazoparib for the treatment of adults with BRCA 1 or 2 mutated HER2-negative locally advanced or metastatic breast cancer after prior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The draft guidance states: ‘When considering the condition’s severity and its effect on quality and length of life, the most likely cost-effectiveness estimates for talazoparib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.

PARP inhibitor talazoparib combined with enzalutamide approved in EU for prostate cancer

9th January 2024

The oral poly ADP-ribose polymerase (PARP) inhibitor talazoparib (brand name Talzenna) has been approved by the European Commission (EC) in combination with the androgen receptor blocker enzalutamide (brand name Xtandi) in eligible patients with prostate cancer, its manufacturer Pfizer has announced.

Indicated for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated. It is now the first and only PARP inhibitor licensed in the European Union for use with enzalutamide for patients with mCRPC, with or without gene mutations.

Preclinical studies have demonstrated that talazoparib blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death.

Robert Jones, professor of clinical cancer research at the University of Glasgow, Scotland, said: ‘New treatment options are needed to increase the proportion of patients with metastatic castration-resistant prostate cancer who can benefit from current anticancer medicines that keep the disease under control for longer.

‘The European Commission’s approval of talazoparib in combination with enzalutamide offers a meaningful advancement for the treatment of patients with metastatic castration-resistant prostate cancer, the most advanced and aggressive stage of the disease.’

Erik Briers, vice chairman of Europa UOMO – a European advocacy movement for people with prostate cancer – added: ‘After years of fighting prostate cancer, it can be devastating for a patient to learn that their cancer has stopped responding to testosterone-lowering treatments. At this stage of the disease, the prognosis is generally poor.

‘Patients urgently need new treatment options and Talzenna in combination with Xtandi can bring new hope to these patients.’

Significant improvement with talazoparib plus enzalutamide

The EC approval is based on data from the Phase 3 TALAPRO-2 trial, a multicentre, randomised, double-blind, placebo-controlled study, which compared the efficacy and safety of talazoparib plus enzalutamide versus enzalutamide alone in patients with asymptomatic or mildly symptomatic mCRPC receiving ongoing androgen deprivation therapy.

Patients were prospectively assessed for homologous recombination repair (HRR) gene alterations in tumour tissue and randomly assigned (1:1) to talazoparib 0.5 mg or placebo, plus enzalutamide 160 mg, administered orally once daily.

Randomisation was stratified by HRR gene alteration status (deficient vs non-deficient or unknown) and previous treatment with life-prolonging therapy (docetaxel or abiraterone, or both: yes vs no) in the castration-sensitive setting.

The results from TALAPRO-2 Cohort 1, published in The Lancet, showed that treatment with talazoparib plus enzalutamide reduced the risk of disease progression or death by 37% versus placebo plus enzalutamide (Hazard Ratio [HR]: 0.63; 95% Confidence Interval [CI], 0.51–0.78; P< 0.0001), meeting the study’s primary endpoint of improving radiographic progression-free survival (rPFS).

A trend in overall survival (OS), a key secondary endpoint, favouring talazoparib plus enzalutamide was also observed, though these data are immature.

The safety of talazoparib plus enzalutamide in the TALAPRO-2 trial was generally consistent with the known safety profile of each medicine.

The researchers concluded that talazoparib plus enzalutamide resulted in clinically meaningful and statistically significant improvement in rPFS versus standard of care enzalutamide as first-line treatment for patients with mCRPC.

Talazoparib is also approved in over 70 countries, including in the EU, as a once-daily monotherapy for the treatment of adult patients with deleterious or suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated (gBRCAm) human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer.

Existing drug could offer new hope for secondary breast cancer that has spread to the brain

13th October 2021

A study funded by the charity Breast Cancer Now will explore if talazoparib (Talzenna) could be used to treat people with incurable metastatic breast cancer that has spread to the brain.

There are limited treatment options for people with breast cancer that has spread to the brain and a lot of drugs are unable to reach these tumours because of the brain’s natural protection, meaning new treatment discoveries are urgently needed.

Talazoparib is an existing PARP inhibitor drug which works by preventing cancer cells with altered BRCA genes from repairing their DNA, forcing them to die. Although the drug is licensed for use in certain patients with BRCA mutated, HER2 negative locally advanced or secondary (metastatic) breast cancer, it hasn’t been assessed for use on the NHS

Now, a team led by Professor Leonie Young and Dr Damir Vareslija from RCSI University of Medicine and Health Sciences will investigate if the drug could be used to treat secondary breast cancer in the brain.

Through previous research, which analysed tumour samples donated by people whose breast cancer has spread to the brain, the team established that almost half of the tumours had changes in the way they repair their DNA and this could make these tumours vulnerable to PARP inhibitors like talazoparib.

Using tumours and breast cancer cells donated by patients, researchers will now test in the lab if talazoparib is effective in treating secondary breast cancer in the brain. Through further tests using mice and sophisticated laboratory models mimicking the brain’s protective system, the researchers will see if the drug can also reach tumours in the brain. The researchers aim to identify key features of a tumour that responds to this type of treatment to establish who could benefit most.

The study is being funded by the Breast Cancer Now Catalyst Programme, which aims to accelerate progress in world-class breast cancer research through innovation and collaboration. As part of the Programme, Pfizer have provided Breast Cancer Now with funding through an independent medical research grant and given the charity’s researchers access to several Pfizer medicines.

Professor Leonie Young, Professor in the Department of Surgery at RCSI University of Medicine and Health Sciences said: “Our previous research has shown that, in many cases, secondary breast cancer tumours in the brain have changes in the way they repair their DNA and we believe this could make them vulnerable to PARP inhibitor drugs like talazoparib.

“People are always at the heart of the research we do and we are always trying to answer questions that are important to our patients. The support of Breast Cancer Now will enable us to learn more about the effectiveness of these powerful drugs to hopefully treat people with secondary breast cancer which has spread to the brain in the future.”

Dr Simon Vincent, Director of Research, Support and Influencing at Breast Cancer Now, said: “An estimated 35,000 people in the UK are living with incurable secondary breast cancer, and the fear and uncertainty around when this devastating disease will cut their lives short. We desperately need to discover new ways to treat this incurable disease, including for those whose breast cancer has spread to the brain and who have very limited treatment options.

“That’s why we’re delighted, this Secondary Breast Cancer Awareness Day, to announce that we’re funding Professor Young’s project through The Breast Cancer Now Catalyst Programme. We hope this study will be successful and lead to effective new treatments for those who badly need them.”