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Talzenna in combination with Enzalutamide for the treatment of adult patients with metastatic castration-resistant prostate cancer in whom chemotherapy is not clinically indicated. Approved in European Union

The European Commission ( EC ) has approved Talzenna ( Talazoparib ), an oral poly ADP-ribose polymerase ( PARP ) inhibitor, in combination with Enzalutamide ( Xtandi ), for the treatment of adult patients with metastatic castration-resistant prostate cancer ( mCRPC ) in whom chemotherapy is not clinically indicated.

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, have shown that treatment with Talazoparib plus Enzalutamide reduces 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 less than 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 Talazoparib plus Enzalutamide had not yet been reached versus 21.9 months for those treated with placebo plus Enzalutamide. 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, favoring 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 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 U.S., 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 Enzalutamide 160mg/day, or placebo plus Enzalutamide 160 mg/day.
The primary endpoint of the trial was radiographic progression-free survival, 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 (t hose with HRRm ). Secondary endpoints included overall survival, objective response rate ( ORR ), duration of response ( DoR ), and PSA response.

Talazoparib is an oral inhibitor of PARP, which plays a role in DNA damage repair. 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.

Metastatic castration-resistant prostate cancer is a cancer that has spread beyond the prostate gland and has progressed despite medical or surgical treatment to lower testosterone. There were approximately 1.4 million new cases of prostate cancer reported worldwide in 2020, of which approximately 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. ( Xagena )

Source: Pfizer, 2024