Pfizer Talzenna in combo with Xtandi gets European approval to treat patients with metastatic castration-resistant prostate cancer

Pfizer Inc. announced that the European Commission (EC) has approved Talzenna (talazoparib), an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with Xtandi (enzalutamide), for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated. With this approval, Talzenna is now the first and only PARP inhibitor licensed in the European Union for use with Xtandi for patients with mCRPC, with or without gene mutations.

“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,” said Robert Jones, MBChB, PhD, Professor of Clinical Cancer Research, University of Glasgow. “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.”

“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,” said Erik Briers, MS, PhD, vice chairman, Europa UOMO, a European advocacy movement for people with prostate cancer. “Patients urgently need new treatment options and Talzenna in combination with Xtandi can bring new hope to these patients.”

This approval by the European Commission of Talzenna in combination with Xtandi for the mCRPC indication is valid in all 27 EU member states plus Iceland, Liechtenstein, and Norway.

The approval is based on data from the phase 3 TALAPRO-2 trial, a multicenter, randomized, double-blind, placebo-controlled study, evaluating two mCRPC patient cohorts: Cohort 1 (all-comers [n=805]) and Cohort 2 (those with HRR gene mutations [HRRm; n=399]). The results from TALAPRO-2 Cohort 1, which were published in The Lancet, showed that treatment with Talzenna plus Xtandi reduced the risk of disease progression or death by 37% versus placebo plus Xtandi (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). At the time of the analysis, the median rPFS for those treated with Talzenna plus Xtandi had not yet been reached versus 21.9 months for those treated with placebo plus Xtandi. Median rPFS is defined as the timepoint in which 50% of patients in each treatment arms have progressed. A trend in overall survival (OS), a key secondary endpoint, favouring Talzenna plus Xtandi was also observed, though these data are immature. The safety of Talzenna plus Xtandi in the TALAPRO-2 trial was generally consistent with the known safety profile of each medicine.

“Today’s approval of Talzenna in combination with Xtandi represents an important advancement for men living with prostate cancer in Europe,” said Chris Boshoff, M.D., Ph.D., chief oncology officer, executive vice president, Pfizer. “The results from the pivotal TALAPRO-2 trial showed that this combination offers an effective treatment that addresses disease progression in patients with or without any specific gene mutation.”

Talzenna in combination with Xtandi was approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with HRR gene-mutated mCRPC in June 2023. Pfizer has also shared the TALAPRO-2 data with other regulatory agencies to support regulatory filings.

Metastatic castration-resistant prostate cancer (mCRPC) is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. There were ~1.4 million new cases of prostate cancer reported worldwide in 2020, of which ~470,000 new cases were in Europe. Approximately 10%–20% of prostate cancer patients develop mCRPC within 5-7 years of diagnosis. Between 1.2%–2.1% of all prostate cancer cases globally are mCRPC.

The phase 3 TALAPRO-2 trial is a two-part, two-cohort, multicenter, randomized, double-blind, placebo-controlled study that enrolled 1,106 patients with mCRPC (with no systemic treatments initiated after documentation of mCRPC) at sites in the US, Canada, Europe, South America, and the Asia-Pacific region. The study included two patient cohorts: all-comers (n=805) and those with and without gene mutations (HRRm; n=399). Patients on androgen deprivation therapy (ADT) or who had bilateral orchiectomy in the trial were randomized to receive Talzenna 0.5 mg/day plus Xtandi 160mg/day, or placebo plus Xtandi 160 mg/day.

The primary endpoint of the trial is radiographic progression-free survival (rPFS), defined as the time from the date of randomization to first objective evidence of radiographic progression by blinded independent review, or death, whichever occurs first, in both Cohort 1 (all-comers) and Cohort 2 (those with HRRm). Secondary endpoints include overall survival (OS), objective response rate, duration of response, and PSA response.

Talzenna (talazoparib) is an oral inhibitor of poly ADP-ribose polymerase (PARP), which plays a role in DNA damage repair. Preclinical studies have demonstrated that Talzenna blocks PARP enzyme activity and traps PARP at the site of DNA damage, leading to decreased cancer cell growth and cancer cell death.

Talzenna is approved in over 70 countries, including the US and 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. In the US, Talzenna is approved in combination with Xtandi (enzalutamide) for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). In the EU, Talzenna is now approved in combination with enzalutamide for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated.

As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for Talzenna.

In combination with enzalutamide for the treatment of adult patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

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