Talazoparib plus enzalutamide approved in EU for mCRPC

The European Commission (EC) has approved the combination of talazoparib (Talzenna) and enzalutamide (Xtandi) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) in whom chemotherapy is not clinically indicated.¹

In the United States, talazoparib plus enzalutamide is approved by the FDA for the treatment of patients with homologous recombination repair gene-mutated mCRPC.

The EC based its approval on findings from thephase 3 TALAPRO-2 trial (NCT033951970), which showed that treatment with talazoparib plus enzalutamide reduced the risk of disease progression or death by 37% versus placebo plus enzalutamide in this patient population (HR, 0.63; 95% CI, 0.51-0.78; P < .0001).² The median rPFS that was not reached (NR; 95% CI, 27.5-NR) in the combination arm (n = 402) compared with 21.9 months (95% CI, 16.6-25.1) for patients in the placebo arm (n = 403). The median follow-up for rPFS was 24.9 months and 24.6 months in the combination and placebo groups, respectively.

“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,” Robert Jones, MBChB, PhD, professor of Clinical Cancer Research, University of Glasgow, stated in a press release.¹ “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.”

In TALAPRO-2, patients were randomly assigned 1:1 to receive talazoparib at 0.5 mg/day plus enzalutamide at 160 mg/day or placebo plus enzalutamide at 160 mg/day.²

Patient characteristics were well balanced between the 2 treatment arms. The median age in both arms was 71 years, and the median prostate-specific antigen (PSA) was 18.2 ng/mL and 16.2 ng/mLin the talazoparib and placebo arms, respectively. Metastatic disease sites included bone (86.8% and 84.9% in the talazoparib and placebo arms, respectively), lymph node (36.6% and 41.4%), visceral lung (11.2% and 15.1%), and visceral liver (3.0% and 4.0%).In the talazoparib and placebo arms, 64.4% and 67.2% of patients had an ECOG performance status of 0, respectively.

The median time to PSA progression was 26.7 months (95% CI, 21.2-30.4) in the talazoparib arm and 17.5 months (95% CI, 14.1-20.8) in the placebo arm (HR, 0.72; 95% CI, 0.58-0.89; P = .002). The median time to cytotoxic chemotherapy was NR (95% CI, 37.0-NR) and NR (95% CI, 32.3-NR) for the talazoparib and placebo groups, respectively (HR, 0.49; 95% CI, 0.38-0.65; P < .0001).

The median PFS2 for talazoparib plus enzalutamide was 36.4 months (95% CI, 33.5-NR) vs 35.3 months (95% CI, 28.6-NR) for placebo plus enzalutamide (HR, 0.77; 95% CI, 0.61-0.98; P = .04).

Evaluable patients treated with talazoparib plus enzalutamide (n = 120) experienced an objective response rate (ORR) of 61.7%, including a complete response (CR) rate of 37.5% and a partial response (PR) rate of 24.2%. The stable disease rate in these patients was 30.0% and the progressive disease rate was 5.8%. The ORR for evaluable patients treated with placebo plus enzalutamide (n = 132) was 43.9%, with a CR rate of 18.2% and a PR rate of 25.8%. The stable disease rate was 28.8% and the progressive disease rate was 22.7%.

Regarding safety, 98.5% and 94.5% of patients experienced any treatment-emergent adverse effect (TEAE) in the talazoparib and placebo arms, respectively. The rates of any treatment-related TEAEs were 89.7% and 69.6%, respectively. Serious AEs were reported in 39.4% of patients in the talazoparib arm, including 19.6% who had serious treatment-related AEs (TRAEs). In the placebo arm, serious AEs and serious TRAEs occurred in 26.7% and 3.0% of patients, respectively.

The most common grade 3/4 TEAE in the combination arm was anemia, which occurred in 46% of patients. For most of these patients, the anemia improved after dose reduction, with only 8% (n = 33) discontinuing talazoparib due to anemia. There were no treatment-related deaths in the combination arm and 2 treatment-related deaths in the control arm.

Although this combination is approved in the EU for patients with mCRPC, regardless of gene mutation status, in the United States, talazoparib plus enzalutamide is approved by the FDA for the treatment of patients with homologous recombination repair gene-mutated mCRPC.³

References

1. European Commission Approves Pfizer’s TALZENNA® in Combination with XTANDI® for Adult Patients with Metastatic Castration-Resistant Prostate Cancer. Accessed January 9, 2024. https://www.businesswire.com/news/home/20231221936013/en/European-Commission-Approves-Pfizer%E2%80%99s-TALZENNA%C2%AE-in-Combination-with-XTANDI%C2%AE-for-Adult-Patients-with-Metastatic-Castration-Resistant-Prostate-Cancer

2. Agarwal N, Azad A, Carles J, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023;402:291-303. doi: 10.1016/S0140-6736(23)01055-3

3. Pfizer’s TALZENNA® in Combination with XTANDI® Receives U.S. FDA Approval. Accessed June 21, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-talzennar-combination-xtandir-receives-us-fda