Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/18570
Título
Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations: TALAPRO-1 Safety Analyses.
Autor(es)
Mehra, Niven | Fizazi, Karim | de Bono, Johann S | Barthélémy, Philippe | Dorff, Tanya | Stirling, Adam | Machiels, Jean-Pascal | Bimbatti, Davide | Kilari, Deepak | Dumez, Herlinde | Buttigliero, Consuelo | van Oort, Inge M | Castro, Elena CNIO | Chen, Hsiang-Chun | Di Santo, Nicola | DeAnnuntis, Liza | Healy, Cynthia G | Scagliotti, Giorgio V
Fecha de publicación
2022
Idioma
Inglés
Tipo de documento
research article
Resumen
The phase II TALAPRO-1 study (NCT03148795) demonstrated durable antitumor activity in men with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). Here, we detail the safety profile of talazoparib. Men received talazoparib 1 mg/day (moderate renal impairment 0.75 mg/day) orally until radiographic progression, unacceptable toxicity, investigator decision, consent withdrawal, or death. Adverse events (AEs) were evaluated: incidence, severity, timing, duration, potential overlap of selected AEs, dose modifications/discontinuations due to AEs, and new clinically significant changes in laboratory values and vital signs. In the safety population (N = 127; median age 69.0 years), 95.3% (121/127) experienced all-cause treatment-emergent adverse events (TEAEs). Most common were anemia (48.8% [62/127]), nausea (33.1% [42/127]), decreased appetite (28.3% [36/127]), and asthenia (23.6% [30/127]). Nonhematologic TEAEs were generally grades 1 and 2. No grade 5 TEAEs or deaths were treatment-related. Hematologic TEAEs typically occurred during the first 4-5 months of treatment. The median duration of grade 3-4 anemia, neutropenia, and thrombocytopenia was limited to 7-12 days. No grade 4 events of anemia or neutropenia occurred. Neither BRCA status nor alteration origin significantly impacted the safety profile. The median (range) treatment duration was 6.1 (0.4-24.9) months; treatment duration did not impact the incidence of anemia. Only 3 of the 15 (11.8% [15/127]) permanent treatment discontinuations were due to hematologic TEAEs (thrombocytopenia 1.6% [2/127]; leukopenia 0.8% [1/127]). Common TEAEs associated with talazoparib could be managed through dose modifications/supportive care. Demonstrated efficacy and a manageable safety profile support continued evaluation of talazoparib in mCRPC. NCT03148795.
Palabras clave
MESH
Aged | Anemia | Antineoplastic Agents | DNA Damage | Humans | Male | Neutropenia | Phthalazines | Poly(ADP-ribose) Polymerase Inhibitors | Prostatic Neoplasms, Castration-Resistant
DOI
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