TY - JOUR
T1 - Development of the PARP inhibitor talazoparib for the treatment of advanced BRCA1 and BRCA2 mutated breast cancer
AU - Hobbs, Evthokia A.
AU - Litton, Jennifer K.
AU - Yap, Timothy A.
N1 - Funding Information:
TA Yap is supported by MD Anderson Cancer Center Support grant (NIH/NCI P30 CA016672), the U.S. Department of Defense Ovarian Cancer Research Program (OC200482), and the V Foundation Clinical Scholar Program (VC2020-001).
Funding Information:
JK Litton has received grant or research support from: Novartis Medivation/Pfizer, Genentech, GlaxoSmithKline, EMD Serono, AstraZeneca, MedImmune, Zenith and Pfizer. She has also served on speaker’s bureaus for MedLearning, Physician’s Education Resource, Prime Oncology, Medscape, Clinical Care Options and Medpage and have received honoraria from UpToDate. JK Litton has also served on the advisory Committees of AstraZeneca, Ayala and Pfizer (uncompensated) and review panels of the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), the National Institutes of Health (NIH), the Physician Data Query (PDQ) and the Society for Immunotherapy of Cancer (SITC). TA Yap, meanwhile, has received research support (granted to his research institution) from Artios, AstraZeneca, Bayer, Clovis, Constellation, Cyteir, Eli Lilly and Company, EMD Serono, Forbius, F-Star, GlaxoSmithKline, Genentech, ImmuneSensor, Ipsen, Jounce, Karyopharm, Kyowa, Merck and Co, Novartis, Pfizer Inc, Ribon Therapeutics, Regeneron, Repare, Sanofi, Scholar Rock, Seattle Genetics, Tesaro, and Vertex Pharmaceuticals. He has also consulted for Almac, Aduro, AstraZeneca, Atrin, Axiom, Bayer, Bristol-Myers Squibb, Calithera, Clovis, Cybrexa, EMD Serono, F-Star, Guidepoint, Ignyta, I-Mab, Jansen Pharmaceuticals, Merck and Co, Pfizer, Repare, Roche, Rubius, Schrodinger, Seattle Genetics, Varian and Zai Labs. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2021
Y1 - 2021
N2 - Introduction: BRCA1 and BRCA2 (BRCA1/2) mutation breast cancers constitute an uncommon, but unique group of breast cancers that present at a younger age, and are underscored by genomic instability and accumulation of DNA damage. Talazoparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor that exploits impaired DNA damage response mechanisms in this population of patients and results in significant efficacy. Based on the results of the EMBRACA trial, talazoparib was approved for the treatment of patients with advanced germline BRCA1/2 mutant breast cancer. Areas covered: In this review, the authors highlight the relevant clinical trials of talazoparib, as well as, safety, tolerability, and quality of life considerations. They also examine putative response and resistance mechanisms, and rational combinatorial therapeutic strategies under development. Expert opinion: Talazoparib has been a major advance in the treatment of germline BRCA1/2 mutation breast cancer with both clinical efficacy and improvement in quality of life compared to standard cytotoxic chemotherapy. To date, the optimal sequencing of talazoparib administration in the metastatic setting has not yet been established. A deeper understanding of response and resistance mechanisms, and more broadly, the DNA repair pathway, will lead to additional opportunities in targeting this pathway and open up therapeutic indications to a broader patient population.
AB - Introduction: BRCA1 and BRCA2 (BRCA1/2) mutation breast cancers constitute an uncommon, but unique group of breast cancers that present at a younger age, and are underscored by genomic instability and accumulation of DNA damage. Talazoparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor that exploits impaired DNA damage response mechanisms in this population of patients and results in significant efficacy. Based on the results of the EMBRACA trial, talazoparib was approved for the treatment of patients with advanced germline BRCA1/2 mutant breast cancer. Areas covered: In this review, the authors highlight the relevant clinical trials of talazoparib, as well as, safety, tolerability, and quality of life considerations. They also examine putative response and resistance mechanisms, and rational combinatorial therapeutic strategies under development. Expert opinion: Talazoparib has been a major advance in the treatment of germline BRCA1/2 mutation breast cancer with both clinical efficacy and improvement in quality of life compared to standard cytotoxic chemotherapy. To date, the optimal sequencing of talazoparib administration in the metastatic setting has not yet been established. A deeper understanding of response and resistance mechanisms, and more broadly, the DNA repair pathway, will lead to additional opportunities in targeting this pathway and open up therapeutic indications to a broader patient population.
KW - Advanced breast cancer
KW - BRCA1/2 mutant
KW - PARP1/2 inhibitor
KW - talazoparib
UR - http://www.scopus.com/inward/record.url?scp=85111578702&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111578702&partnerID=8YFLogxK
U2 - 10.1080/14656566.2021.1952181
DO - 10.1080/14656566.2021.1952181
M3 - Article
C2 - 34309473
AN - SCOPUS:85111578702
SN - 1465-6566
VL - 22
SP - 1825
EP - 1837
JO - Expert opinion on pharmacotherapy
JF - Expert opinion on pharmacotherapy
IS - 14
ER -