Abstract 1407P
Background
Novel hormonal agents (NHAs), eg, abiraterone and enzalutamide, are standard treatment (tx) for mCRPC, but many pts develop drug resistance (some due to AR mutations) and have poor prognosis. This retrospective study evaluated real-world detection rates of AR T878 and/or H875 mutations and compared outcomes in pts whose tumors harbored these mutations (AR 878/875+) and those whose did not (AR 878/875-).
Methods
Pts (aged ≥18 y) in the US with mCRPC (Mar 11, 2014–Jun 30, 2021) were identified in the GuardantINFORM database, which combines genomic information from Guardant360 tests with real-world administrative claims data. Matched (1:2) cohorts of AR 878/875+ and AR 878/875- pts were created based on age (±5 y), Elixhauser comorbidity index weighted score (±1 SD), NHA prior to first-line (1L) mCRPC, and earliest year of metastatic diagnosis (±1 y). Outcomes were compared in unmatched AR 878/875+ vs AR 878/875- cohorts and in matched AR 878/875+ pts who had the mutation detected prior to 1L mCRPC tx vs AR 878/875- pts.
Results
In all, 7056 pts with mCRPC who received ≥1 Guardant360 test were identified; 774 (11%) were AR 878/875+ and 6282 (89%) were AR 878/875-. In unmatched cohorts of AR 878/875+ vs AR 878/875- pts, median (95% CI) real-world overall survival (rwOS) from mCRPC diagnosis was 46.6 mo (43.0–51.2) vs 51.6 mo (50.1–54.2; P=0.1953). Matched cohorts included 409 AR 878/875+ pts (91 had mutation detected prior to 1L mCRPC tx) and 818 AR 878/875- pts. In matched cohorts of AR 878/875+ vs AR 878/875- pts, median (95% CI) rwOS from 1L initiation was 16.1 mo (11.4–26.8) vs 50.7 mo (45.4–59.8; P<0.0001); time to next tx (TTNT) was 5.0 mo (4.1–7.2) vs 11.7 mo (9.7–14.4; P=0.0183). In subgroups of matched AR 878/875+ and AR 878/875- pts who received NHA-containing 1L tx (n=20 vs 309), median (95% CI) rwOS from 1L initiation was 16.4 mo (6.9–not reached [NR]) vs 59.9 mo (43.5–NR; P=0.0007); TTNT was 4.5 mo (1.8–13.1) vs 13.9 (9.1–20.9; P=0.0274).
Conclusions
In this real-world study, 11% of pts with mCRPC were AR 878/875+ by circulating tumor DNA testing. By matched comparative analysis, rwOS and TTNT were significantly shorter in AR 878/875+ vs AR 878/875- pts, indicating an unmet need for this population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Arvinas Androgen Receptor, Inc.
Funding
Arvinas Androgen Receptor, Inc.
Disclosure
T.F. Stewart: Financial Interests, Personal, Advisory Board: Seattle Genetics/Astellas; Financial Interests, Personal, Funding: GRAIL. R. Gedrich, D. Chirnomas, M. Edwards: Financial Interests, Personal, Full or part-time Employment: Arvinas, Inc.; Financial Interests, Personal, Stocks/Shares: Arvinas, Inc. J. Saha: Financial Interests, Personal, Full or part-time Employment: Guardant Health; Financial Interests, Personal, Stocks/Shares: Guardant Health. J. Lang: Financial Interests, Personal, Advisory Board: Pfizer, Janssen, Gilead, 4D Pharma, Arvinas, Inc., Astellas, Myovant, AstraZeneca, Seagen; Non-Financial Interests, Institutional, Principal Investigator: Gilead, Pfizer, Arvinas, Inc., Seagen.