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.