Abstract 1373P
Background
Intensification of androgen deprivation therapy (ADT) with docetaxel or androgen receptor axis-targeted therapy (ARAT: abiraterone, apalutamide, enzalutamide) is the current standard of care for pts with mCSPC. However, biomarkers to guide treatment selection are lacking. We previously showed that dn-mCSPC pts with mtSPOP had improved survival outcomes with ADT (PMID: 32624276). Here, we hypothesized that mtSPOP would be associated with improved outcomes with ARAT + ADT but not with docetaxel + ADT.
Methods
This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine Prostate Cancer clinico-genomic database (FH-FMI CGDB), with de-identified data originating from approximately 280 US cancer clinics (∼800 sites of care). Inclusion criteria: dn-mCSPC, tissue biopsy within 90 days of diagnosis, and initiation of ARAT or docetaxel + ADT within 120 days of diagnosis. Time to castration-resistance (TTCR) and overall survival (OS), indexed from metastatic diagnosis, were evaluated with Cox proportional hazards models adjusted for baseline prognostic factors such as PSA and ECOG. OS risk intervals were left truncated to date of comprehensive genomic profiling report to adjust for immortal time.
Results
Of 4089 pts in FH-FMI CGDB, 423 met inclusion criteria. 215 received ADT + ARAT and 208 ADT + docetaxel. 37 pts (8.7%) were mtSPOP(+). Results are summarized in the table. Pts with mtSPOP receiving ARAT had improved median TTCR and OS compared to wild-type SPOP (wtSPOP). Conversely, SPOP status was not associated with outcomes on docetaxel. Tests for treatment interaction were significant. Table: 1373P
| Outcome by treatment type | ARAT (adjusted HR, 95% CI, P) | Docetaxel (adjusted HR, 95% CI, P) |
| Median TTCR, in months; mtSPOP vs wtSPOP | NR vs. 17.7 (0.22; 0.07–0.69, p=0.01) | 18.8 vs 16 (0.83; 0.44–1.58, p=0.58) Pinteraction = 0.03 |
| Median OS, in months; mtSPOP vs wtSPOP | NR vs 27 (0.23, 0.06–0.93; p=0.04) | 26.9 vs 33 (1.44; 0.69–3.00; p=0.33) Pinteraction = 0.03 |
NR = Not Reached.
Conclusions
In this real-world analysis, mtSPOP was associated with improved outcomes with ADT+ARAT (but not ADT+docetaxel) in dn-mCSPC pts. Based on these results, SPOP status may represent a predictive biomarker guiding treatment selection in dn-mCSPC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
U. Swami: Financial Interests, Personal, Advisory Role: Astellas, Exelixis, Seattle Genetics; Financial Interests, Institutional, Funding: Janssen, Exelixis, Astellas/Seattle Genetics. R. P. Graf, V. Fisher, H. Tukachinsky, G.R. Oxnard: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine, Inc.; Financial Interests, Personal, Stocks/Shares: Roche. G. Li: Financial Interests, Personal, Full or part-time Employment: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche AG. E.S. Antonarakis: Financial Interests, Personal, Advisory Role: Janssen, Astellas, Sanofi, Dendreon, Bayer, BMS, Amgen, ESSA, Constellation, Blue Earth, Exact Sciences, Invitae, Curium, Pfizer, Merck, AstraZeneca, Clovis, Eli Lilly; Financial Interests, Personal, Research Grant: Janssen, J&J, Sanofi, BMS, Pfizer, AstraZeneca, Novartis, Curium, Constellation, ESSA, Celegne, Merck, Bayer, Clovis; Financial Interests, Personal, Other, Co-inventor of AR-V7 technology licensed to Qiagen: Qiagen. N. Agarwal: Financial Interests, Personal, Advisory Role: Astellas, AstraZeneca, Aveo, Bayer, Bristol Myers Squibb, Calithera, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Foundation Medicine, Genentech, Gilead, Janssen, Merck, MEI Pharma, Nektar, Novartis, Pfizer, Pharmacyclics, Seattle Genetics; Financial Interests, Institutional, Funding: Astellas, AstraZeneca, Bavarian Nordic, Bayer, Bristol Myers Squibb, Calithera, Celldex, Clovis, Eisai, Eli Lilly, EMD Serono, Exelixis, Genentech, Gilead, Glaxo Smith Kline, Immunomedics, Janssen, Medivation, Merck, Nektar, New Link Genetics, Novartis. All other authors have declared no conflicts of interest.