Talazoparib

(Talzenna®)

Talzenna®

Drug updated on 10/29/2024

Dosage FormCapsule (oral; 0.1 mg, 0.25 mg, 0.35 mg, 0.5 mg, 0.75 mg, 1 mg)
Drug ClassPoly (ADP-ribose) polymerase (PARP) inhibitors
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • Indicated as a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer
  • Indicated in combination with enzalutamide for the treatment of adult patients with HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

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Summary
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  • This summary is based on the review of 16 systematic review(s)/meta-analysis(es). [1-16]
  • Radiographic Progression-Free Survival (rPFS) and Overall Survival (OS): No significant difference in Event-Free Survival (EFS) or Overall Survival (OS) was observed between intermittent PEG-asparaginase (eight doses) and continuous PEG-asparaginase (15 doses) in non-high-risk acute lymphoblastic leukemia (ALL) patients, as well as between low-risk standard treatment with additional PEG-asparaginase (six doses) and standard treatment (two doses), with risk ratios (RR) close to 1. In metastatic castration-resistant prostate cancer (mCRPC), olaparib demonstrated a significant improvement in rPFS with a hazard ratio (HR) of 0.67 (95% CI: 0.46-0.96) when compared to niraparib and talazoparib, while no significant differences were observed in OS among these treatments. Talazoparib plus enzalutamide had a lower probability of being the most effective for rPFS (13%) and OS (19%) compared to a nonstandard dose of docetaxel.
  • Progression-Free Survival (PFS) and Overall Survival (OS) in BRCA-Mutated Metastatic Breast Cancer (MBC): Both olaparib and talazoparib significantly improved PFS with HRs of 0.64 and 0.54, respectively, compared to standard chemotherapy; however, there were no significant differences in OS.
  • Combination Therapies: PARP inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSI) combinations improved rPFS (HR: 0.62) and OS (HR: 0.84) compared to ARSI alone in mCRPC.
  • Objective Response Rate (ORR) in BRCA-Mutated HER2-Negative MBC: Both olaparib and talazoparib exhibited higher ORRs than standard chemotherapy, indicating greater efficacy in this population.
  • Hematological Toxicities: Talazoparib significantly increased the risk of all grades and ≥G3 anemia, neutropenia, and thrombocytopenia compared to non-PARP inhibitors. It also presented a higher risk of treatment interruption and dose reduction due to adverse events compared to other PARP inhibitors.
  • Adverse Events (AEs): Talazoparib had a higher incidence of grade ≥3 adverse events, with an odds ratio of 3.7 when compared to olaparib and niraparib. In contrast, olaparib and rucaparib did not significantly increase the incidence of grade ≥3 AEs.
  • Serious AEs (SAEs) and Discontinuation: There were no significant differences in the occurrence of serious adverse events or discontinuation related to adverse events among olaparib, rucaparib, niraparib, and talazoparib.
  • BRCA-Mutated Populations: There is significant efficacy of PARP inhibitors (PARPis), including talazoparib, in BRCA-positive patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic breast cancer (MBC), with additional evidence of efficacy for PARPi combined with ARSI in HRR-proficient mCRPC. Careful monitoring for increased hematological toxicities is recommended for patients using talazoparib, especially in those with mCRPC.

Product Monograph / Prescribing Information

Document TitleYearSource
Talzenna (talazoparib) Prescribing Information.2024Pfizer Inc., New York, NY

Systematic Reviews / Meta-Analyses

Document TitleYearSource
Efficacy and safety of PARP inhibitors in the treatment of prostatic cancer: a systematic review and network meta-analysis2024Chinese Clinical Oncology
Predicting Treatment Effects from Surrogate Endpoints in Historical Trials in First-Line Metastatic Castration-Resistant Prostate Cancer2024Clinical Genitourinary Cancer
Feasibility of Indirect Treatment Comparisons Between Niraparib Plus Abiraterone Acetate and Other First-Line Poly ADP-Ribose Polymerase Inhibitor Treatment Regimens for Patients with BRCA1/2 Mutation-Positive Metastatic Castration-Resistant Prostate Cancer2024Advances in Therapy
Hematological Toxicity of PARP Inhibitors in Metastatic Prostate Cancer Patients with Mutations of BRCA or HRR Genes: A Systematic Review and Safety Meta-analysis2024Targeted Oncology
Poly (ADP-ribose) Polymerase Inhibitors Have Comparable Efficacy with Platinum Chemotherapy in Patients with BRCA-positive Metastatic Castration-resistant Prostate Cancer. A Systematic Review and Meta-analysis2024European Urology Oncology
Combining PARP Inhibitors and Androgen Receptor Signalling Inhibitors in Metastatic Prostate Cancer: A Quantitative Synthesis and Meta-analysis2024European Urology Oncology
Hematological Toxicities with PARP Inhibitors in Prostate Cancer: A Systematic Review and Meta-Analysis of Phase II/III Randomized Controlled Trials2023Cancers
PARP Inhibitors for the Treatment of BRCA1/2-Mutated Metastatic Breast Cancer: A Systematic Review and Meta-analysis2023Hematology/Oncology and Stem Cell Therapy
PARP-inhibitors for BRCA1/2-related advanced HER2-negative breast cancer: A meta-analysis and GRADE recommendations by the Italian Association of Medical Oncology2022Breast
Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer2022Cancer Treatment Reviews
Effect and Safety of Therapeutic Regimens for Patients With Germline BRCA Mutation-Associated Breast Cancer: A Network Meta-Analysis2021Frontiers in Oncology
Comparative safety and tolerability of approved PARP inhibitors in cancer: A systematic review and network meta-analysis2021Pharmacological Research
Endocrine Treatment and Targeted Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: ASCO Guideline Update2021Journal of Clinical Oncology
Poly (ADP-ribose) polymerase inhibitors in solid tumours: Systematic review and meta-analysis2021European Journal of Cancer
Comparative efficacy, safety, and acceptability of single-agent poly (ADP-ribose) polymerase (PARP) inhibitors in BRCA-mutated HER2-negative metastatic or advanced breast cancer: a network meta-analysis2020Aging
PARP inhibitors as a new therapeutic option in metastatic prostate cancer: a systematic review2020Prostate Cancer and Prostatic Diseases

Clinical Practice Guidelines