Johann S. de Bono, MD, PhD
According to results from a phase II trial presented by Johann S. de Bono, MD, PhD, and colleagues at the 2020 Genitourinary (GU) Cancers Symposium (Abstract 119), treatment with the poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib showed antitumor activity in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. Talazoparib especially showed activity in patients with a BRCA mutation.
Talazoparib is unique in that it also traps PARP on DNA, interfering with cancer cell replication. This novel treatment targets cancer cells while selectively sparing normal cells.
TALAPRO-1
The phase II TALAPRO-1 trial is enrolling approximately 100 patients with measurable soft-tissue disease, progressive metastatic castration-resistant prostate cancer, and DNA damage repair mutations such as those in ATM, ATR, BRCA1, BRCA2, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, and RAD51C. Enrolled patients must have received one or two chemotherapy regimens previously and progressed on one or more novel hormonal therapy.
KEY POINTS
- The overall objective response rate was 25.6%.
- The objective response rate for patients with BRCA1/2 mutations was 50.0% and was 7.1% for those with ATM mutations.
Current Analysis
In the presented analysis, 81 patients with metastatic castration-resistant prostate cancer and DNA damage repair mutations received 1 mg/d of oral talazoparib as of June 5, 2019. Patients were assessed until radiographic progression, unacceptable toxicity, or consent withdrawal.
The primary endpoint was objective response rate (ORR; blinded independent review). A planned interim analysis of safety and efficacy was performed after 20 patients with BRCA1/2 mutations who received treatment for at least 8 weeks. Forty-three patients enrolled by February 12, 2019, were evaluable for the primary endpoint of objective response rate—20 had a BRCA1/2 mutation; 2, a PALB2 mutation; 14, an ATM mutation; and 7, another mutation.
The overall objective response rate was 25.6% (95% confidence interval = 13.5%–41.2%). The objective response rate for patients with BRCA1/2 mutations was 50.0% and was 7.1% for those with ATM mutations. The median progression-free survival based on radiographic findings was 5.6 months overall and 8.2 months for patients with BRCA1/2 mutations and 3.5 months for those with ATM mutations. The most common treatment-emergent adverse events were anemia, nausea, asthenia, decreased appetite, constipation, and decreased platelet count.
The study authors concluded, “Talazoparib monotherapy demonstrates encouraging antitumor activity in docetaxel-pretreated [patients with] metastatic-castration resistant prostate cancer, especially those with BRCA1/2-mutant [disease], and was generally well tolerated.”
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
