Talazoparib active, safe among subset of men with metastatic prostate cancer - Healio

Talazoparib monotherapy induced promising antitumor activity in men with metastatic castration-resistant prostate cancer who previously received docetaxel, according to the first interim analysis of the single-arm, phase 2 TALAPRO-1 study presented at Genitourinary Cancers Symposium.

The poly(ADP-ribose) polymerase (PARP) inhibitor appeared well-tolerated overall and particularly effective for men with BRCA1 or BRCA2 mutations, Johann S. De Bono, MD, PhD, MB, FRCP, head of the division of clinical studies and professor of experimental cancer medicine at The Institute of Cancer Research in the United Kingdom, and colleagues noted.

Previous studies have demonstrated the efficacy of PARP inhibitors among men with metastatic castration-resistant prostate cancer and DNA damage repair (DDR) mutations who received prior hormonal therapy. Talazoparib (Talzenna, Pfizer Oncology) differs from other PARP inhibitors in that it traps PARP on DNA, inhibiting replication of cancer cells.

Researchers of TALAPRO-1 seek to enroll 100 men with metastatic castration-resistant prostate cancer and DDR mutations likely to be sensitive to PARP inhibition. Trial requirements include receipt of one or two prior chemotherapy regimens and progression on one or more novel hormonal therapies, such as enzalutamide (Xtandi; Pfizer, Astellas) or abiraterone acetate (Zytiga, Janssen).

As of June 5, 81 men in the trial received treatment with oral talazoparib at a dose of 1 mg daily until radiographic progression, unacceptable toxicity or withdrawal of consent. All the men had received docetaxel previously, and about half (49%) also had been treated with cabazitaxel.

Objective response rate per blinded independent review served as the study’s primary endpoint. Time to objective response, duration of response, PSA decrease of 50% or more, circulating tumor cell count conversion to zero and less than five per 7.5 mL of blood, time to PSA progression, radiographic PFS, OS, safety, patient-reported outcomes and pharmacokinetics all served as secondary endpoints.

Results among 43 men evaluable for the primary endpoint showed ORRs of 25.6% (95% CI, 13.5-41.2) overall, 50% (95% CI, 27.2-72.8) for men with BRCA1 or BRCA2 mutations (n = 20), and 7.1% (95% CI, 0.2-33.9) for men with ATM mutations (n = 14).

Median radiographic PFS was 5.6 months (95% CI, 3.5-8.2) overall, 8.2 months (95% CI, 5.6-not estimated) for men with BRCA1 or BRCA2 mutations, and 3.5 months (95% CI, 1.7-8.1) for men with ATM mutations.

Common adverse events related to treatment included anemia, nausea, asthenia, decreased appetite, constipation and a decreased platelet count. – by John DeRosier

Reference:

De Bono JS, et al. Abstract 119. Presented at: Genitourinary Cancers Symposium; Feb. 13-15, 2020; San Francisco.

Disclosures: Pfizer funded this study. De Bono reports honoraria from, consultant/advisory roles with, research funding from and/or travel expenses from Astellas Pharma, AstraZeneca, Bayer, BioXCel Therapeutics, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eisai, Genentech/Roche, Genmab, GlaxoSmithKline, Janssen Oncology, MedImmune, Medivation, Menarini Silicon Biosystems, Merck Serono, Merck Sharp & Dohme, Orion Pharma GmbH, Pfizer, Qiagen, Sanofi, Sierra Oncology and Taiho Pharmaceutical and Vertex. Please see the abstract for all other authors’ relevant financial disclosures.