On behalf of TALAPRO-1 investigators, Prof. Johann de Bono presented on 13 February at 2020 Genitourinary Cancers Symposium held in San Francisco, US, the results of first interim analysis of the phase II trial with PARP inhibitor talazoparib performed among patients with DNA damage repair (DDR) mutations and docetaxel pretreated metastatic castration-resistant prostate cancer (mCRPC). The study team found that monotherapy with talazoparib demonstrated encouraging antitumour activity in this population, especially in patients with BRCA1/2 mutations. The treatment was well tolerated.
The authors wrote in the study background that phase II and III studies with PARP inhibitors have demonstrated antitumour activity in patients with mCRPC with DDR mutations and who were previously treated with novel hormonal therapy. Talazoparib is a potent inhibitor and trapper of PARP.
TALAPRO-1 (NCT03148795) is planned to enroll approximately 100 patients with measurable soft tissue disease, progressive mCRPC, and DDR mutations likely to sensitize to PARP inhibitors, including ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, RAD51C.
Enrollment was planned for patients who received 1–2 chemotherapy regimens from which at least one being taxane-based and who progressed on at least one novel hormonal therapy, in particular enzalutamide or abiraterone acetate.
In the study, patients receive oral talazoparib 1 mg per day and in case of moderate renal impairment the dose was adjusted to 0.75 mg per day. Patients are treated until radiographic progression, unacceptable toxicity, or consent withdrawal.
The study primary endpoint is objective response rate (ORR) according blinded independent review. Secondary endpoints are time to OR, duration of response, prostate-specific antigen (PSA) decrease ≥50%, circulating tumour cell (CTC) count conversion to 0 and <5 per 7.5 mL of blood, time to PSA progression, radiographic progression-free survival (rPFS), overall survival, safety, patient reported outcomes, and pharmacokinetics.
A planned interim analysis of safety and efficacy was performed after 20 patients with BRCA1/2 mutations were on treatment for ≥8 weeks.
As of 5th June 2019, in total 81 patients received talazoparib and 43 patients enrolled by 12th February 2019 were evaluable for the primary endpoint, of those 20 with BRCA1/2, 2 with PALB2, 14 with ATM, and 7 with other mutations.
All included patients received prior docetaxel treatment and 49% prior cabazitaxel.
The ORR was 25.6% (95% confidence interval [CI] 13.5–41.2). The ORR in patients with BRCA1/2 mutations was 50.0% (27.2–72.8), and ORR in patients with ATM was 7.1% (0.2–33.9).
Overall median rPFS was 5.6 months (95% CI 3.5–8.2), while rPFS in patients with BRCA1/2 mutations was 8.2 months (5.6–NE), and 3.5 months (1.7–8.1) in patients with ATM mutations.
Most common treatment-emergent adverse events (≥20%) were anaemia, nausea, asthenia, decreased appetite, constipation, and decreased platelet count.
The authors concluded that treatment with talazoparib shows encouraging antitumour activity in patients with docetaxel-pretreated mCRPC, especially in those with BRCA1/2 mutations.
The study was sponsored by Pfizer Inc.
De Bono JS, Mehra N, Higano CS, et al. TALAPRO-1: A phase II study of talazoparib (TALA) in men with DNA damage repair mutations (DDRmut) and metastatic castration-resistant prostate cancer (mCRPC)—First interim analysis (IA). J Clin Oncol 2020; 38:(suppl 6; abstr 119).