TY - JOUR
T1 - Talazoparib, a Poly(ADP-ribose) Polymerase Inhibitor, for Metastatic Castration-resistant Prostate Cancer and DNA Damage Response Alterations
T2 - TALAPRO-1 Safety Analyses
AU - Mehra, Niven
AU - Fizazi, Karim
AU - De Bono, Johann S.
AU - Barthélémy, Philippe
AU - Dorff, Tanya
AU - Stirling, Adam
AU - Machiels, Jean Pascal
AU - Bimbatti, Davide
AU - Kilari, Deepak
AU - Dumez, Herlinde
AU - Buttigliero, Consuelo
AU - Van Oort, Inge M.
AU - Castro, Elena
AU - Chen, Hsiang Chun
AU - Di Santo, Nicola
AU - Deannuntis, Liza
AU - Healy, Cynthia G.
AU - Scagliotti, Giorgio V.
N1 - Publisher Copyright:
© 2022 The Author(s).
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Background: 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. Patients and Methods: 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. Results: 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]). Conclusion: 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.
AB - Background: 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. Patients and Methods: 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. Results: 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]). Conclusion: 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.
KW - BRCA
KW - PARP inhibitor
KW - castration-resistant prostatic cancer
KW - talazoparib
UR - http://www.scopus.com/inward/record.url?scp=85139536391&partnerID=8YFLogxK
U2 - 10.1093/oncolo/oyac172
DO - 10.1093/oncolo/oyac172
M3 - Article
C2 - 36124924
AN - SCOPUS:85139536391
SN - 1083-7159
VL - 27
SP - E783-E795
JO - Oncologist
JF - Oncologist
IS - 10
ER -