A study of sustained androgen signaling dependence in metastatic castrate resistant prostate cancer (mCRPC)

ABSTRACT

Background: Advanced androgen signaling inhibition, a prevailing therapy approach in advanced prostate cancer, incurs variable response. Therapy selection guided by predictors is an unmet need. Methods: We reviewed MDACC GU department and Hellenic Sister Institute records for Abiraterone Acetate (AA) treated mCRPC patients (pts) with extraordinary response (absence of radiographic/clinical progression for ≥3 years). We compared to reported findings for COU-AA-302 and real world experience to identify candidate predictors of outcome. We applied a previously proposed COU-AA-302 response prognostic model. Archived diagnostic and subsequent tumor specimens were retrieved for molecular characterization. Results: Forty four of 430 reviewed mCRPC pts had extraordinary response. Table depicts features. Median time to AA discontinuation was 5.8 yr (range 3-12.5+) and 20 pts are on treatment. Safety profile is acceptable with no overt increase in fractures or cardiovascular, metabolic morbidity. All pts experienced >50% PSA decline with nadir ≤0.1 in 80%, occurring within 5mo (median) (range <1-57). Median time to PSA progression 5.9 yr (95% CI 4.4-7.5), median rPFS 11.5 yr. Median OS 9.4 yr (95% CI 8.1-10.7). Pretreatment features differed significantly from other datasets for Longer time from cancer diagnosis (median 8.5 yr), longer time to CRPC (median 3.1 yr), bone metastatic burden (63% ≤3 lesions), and PSA (median 5.5 yr). We applied the model to the cohort and it predicted only 7/44 (16%). Tissue analyses to be reported at meeting due to COVID19 research shutdown. [Formula presented] Conclusions: Extraordinary response to enhanced androgen signaling inhibition in mCRPC appears linked to androgen signaling ‘addiction’ and limited disease volume. Available prognostic models are not sensitive enough to guide selection. Routine biopsy derived predictors will help guide therapeutic strategies and improve curative fraction in advanced prostate cancer. Ref https//doi.org/10.1016/j.clgc.2017.07.014. Clinical trial identification MDACC PA16-0736. Legal entity responsible for the study The authors. Funding: Has not received any funding. Disclosure S.K. Subudhi Advisory/Consultancy Valeant;Honoraria (self), Advisory/Consultancy Dendreon;Honoraria (self), Advisory/Consultancy, and Ownership interest Apricity Health;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution) Janssen;Honoraria (self), Advisory/Consultancy Polaris;Advisory/Consultancy Amgen;Advisory/Consultancy Bayer;Advisory/Consultancy Exelixis;Research grant/Funding (institution) Bristol-Myers-Squibb;Research grant/Funding (institution) AstraZeneca;Honoraria (self) Compugen;Honoraria (self) Parker Institute of Cancer Immunotherapy;Honoraria (self) Society for Immunotherapy od Cancer. C. Logothetis Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution) Janssen;Research grant/Funding (institution) Bristol-Myers-Squibb;Advisory/Consultancy, Research grant/Funding (institution) Pfizer. E. Efstathiou Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses Sanofi;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses Janssen;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses Astellas;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses Tolmar;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses Bayer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses Merck;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses AstraZeneca;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses Pfizer;Honoraria (self), Advisory/Consultancy, Research g ant/Fun ing (institution), Travel/Accommodation/Expenses Oric. All other authors have declared no conflicts of interest.