The optimal treatment for poor prognosis mCRPC is undefined and includes either taxane chemotherapy or androgen receptor (AR) targeted therapy, emphasizing the need for predictive biomarkers.
Patients (pts) with poor prognosis (liver metastases, early CRPC (<12 months from ADT start), and/or >3 of 6 poor prognostic criteria (Chi et al, Annals of Oncol, 2016)) were randomized to receive CAB (Arm A) or AR targeted therapy (Arm B, ABI or ENZ by investigator choice) with cross over at progression. No prior ABI or ENZ was permitted, but prior docetaxel allowed. Primary objective was to determine the clinical benefit rate (CBR) (PSA decline ≥50% (PSA50), objective response (OR), or stable disease (SD) ≥ 12 weeks). Other endpoints included time to PSA progression (TTPP), time to progression (TTP), and overall survival (OS). Serial plasma was sampled for circulating tumour DNA (ctDNA).
95 pts were randomized (Arm A: 45, Arm B: 50). Poor prognosis was based on liver mets in 18%, early CRPC in 88%, and 30% by prognostic criteria. Other baseline factors: median age 68 years, elevated LDH in 41%, elevated ALK PHOS in 52%, ECOG PS 0-1 in 94%, 52% had prior docetaxel (half for castration sensitive disease). Median duration of therapy was 5.8 months (m) for Arm A and 4.5 m for Arm B. Treatment discontinuation reasons included disease progression (A vs B: 40% vs 46%) and toxicity (11% vs 4%). Outcomes are summarized in table. In 58 pts with available results, baseline ctDNA fraction >2% correlated with TTP (median 3.4 m vs 10.8 m, p = 0.011) and OS (median 15.5 m vs not reached (NR), p = 0.002). Genomic alterations in AR, RB1, TP53, PI3K pathway, and DNA repair were present in 69%, 36%, 51%, 40%, and 15%.Table: 792O
|Arm A (CAB)||Arm B (ABI/ENZ)||HR (95% CI)||P|
|SD > 12 weeks (%)||62||46||0.15|
|Median TTPP (m)||7.4||4.8||0.73 (0.42-1.29)||0.28|
|Median TTP (m)||5.3||4.1||0.86 (.53-1.40)||0.56|
|Median OS (m)||NR||15.5||0.56 (0.25-1.22)||0.14|
Treatment with CAB vs ABI/ENZA resulted in similar outcomes. There was a trend in favour of CAB for survival. Genomic correlations will be presented.
Clinical trial identification
Legal entity responsible for the study
Kim N. Chi and BC Cancer.
Sanofi Genzyme, Prostate Cancer Canada Movember Disxcovery Grant, Canadian Institutes of Health Research Project Grant, Terry Fox Research Institute Program Project Grant.
K.N. Chi: Honorarium, grant support: Sanofi Genzyme. N. Iqbal: Honorarium: Janssen, Astellas. M. Ong: Honorarium: Sanofi Genzyme, Janssen, Astellas. S.J. Hotte: Honorarium, advisory board, grant support: Janssen, Astellas. B. Tran: Consulting, honorarium, research grant support: Sanofi Genzyme, Janssen, Astellas. A. Azad: Honorarium: Sanofi, Janssen, Astellas; Grant: Astellas. S. North: Honorarium: Sanofi Genzyme, Janssen, Astellas. C.V. Pezaro: Honoraria, education support: Janssen, Astellas. S.S. Sridhar: Honorarium, grant support: Sanofi Genzyme, Janssen, Astellas. All other authors have declared no conflicts of interest.