Differential responses to taxanes and PARP inhibitors (PARPi) in ATM- versus BRCA2-mutated metastatic castrate-resistant prostate cancer (mCRPC) patients (pts)

Autor: A. Oliver Sartor, Nabil Adra, Ajjai Alva, Mary-Ellen Taplin, Heather H. Cheng, Christopher Su, Marcin Cieslik, Rahul Aggarwal, Heather McClure, Emily Nizialek, Alexandra O. Sokolova, Cora N. Sternberg, Pedro C. Barata, Panagiotis J. Vlachostergios, Ryan Ashkar, Jacob E. Berchuck, Emmanuel S. Antonarakis, Nellie Nafissi, Alan H. Bryce
Rok vydání: 2021
Předmět:
Zdroj: Journal of Clinical Oncology. 39:5040-5040
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2021.39.15_suppl.5040
Popis: 5040 Background: PARPi have shown promise in mCRPC pts with mutations in DNA repair, but ATM- and BRCA2-altered pts may respond differently to PARPi. We hypothesized that differences may also exist for taxane therapy, aiding in treatment sequencing decisions. Methods: mCRPC pts (N = 137) with deleterious ATM or BRCA2 mutations who received taxanes, PARPi, or both were identified from 8 US academic centers. Demographic, treatment, and survival data were collected. Kaplan-Meier analyses were performed for time-to-treatment-discontinuation (TTD), as well as overall survival (OS), from time of first taxane or PARPi therapy. Cox hazard ratio (HR) regression analyses were performed, adjusting for Gleason sum (≤7 vs. 8-10). For OS, receipt of subsequent therapies following first taxane or PARPi was also included as a covariate. Results: 50 ATM- and 87 BRCA2-mutated pts were identified. 40/50 (80%) of ATM-mutated pts received taxane only or taxane prior to PARPi, while 10/50 (20%) received PARPi only or PARPi prior to taxane. ATM-mutated pts showed a trend towards longer TTD when taxane was given first vs PARPi given first (P = 0.08, adjusted HR for taxane treatment 0.50 [95% CI: 0.24–1.08]). Considering all pts who received taxane first, ATM-mutated pts had longer TTD than BRCA2-mutated pts who received taxane first ( P= 0.04, adjusted HR for ATM 0.61 [CI: 0.37–0.99]). Among ATM-mutated pts, OS was longer in those receiving taxane first ( P= 0.06, adjusted HR for taxane treatment 0.33 [CI: 0.10–1.05]). Among BRCA2-mutated pts, 43/87 (49%) received taxane first and 44/87 (51%) received PARPi first. BRCA2-mutated pts had longer TTD when PARPi was given first vs taxane given first ( P< 0.0001, adjusted HR for PARPi treatment 0.32 [CI: 0.19–0.56]). Considering all pts who received PARPi first, BRCA2-mutated pts also had longer TTD than ATM-mutated pts who received PARPi first ( P= 0.0031, adjusted HR for BRCA2 0.29 [CI: 0.12–0.66]). There was no significant OS difference in BRCA2-mutated pts regarding which treatment was given first ( P= 0.63, adjusted HR for PARPi treatment 1.18 [CI: 0.59–2.35]). Conclusions: Our data in ATM- and BRCA2-mutated mCRPC pts suggests a trend towards improved clinical outcomes when taxanes are used prior to PARPi in ATM-mutated pts, while the reverse sequence appears to be better for BRCA2-mutated pts.[Table: see text]
Databáze: OpenAIRE
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