A Randomized Phase 2 Study of Cabazitaxel (CAB) vs (ABI) Abiraterone or (ENZ) Enzalutamide in Poor Prognosis Metastatic Castration-Resistant Prosta...

Date 19 October 2018
Event ESMO 2018 Congress
Session Proffered paper session - Genitourinary tumours, prostate
Topics Anticancer Agents
Prostate Cancer
Presenter Kim Chi
Citation Annals of Oncology (2018) 29 (suppl_8): viii271-viii302. 10.1093/annonc/mdy284
Authors K.N. Chi1, S. Taavitsainen2, N. Iqbal3, C. Ferrario4, M. Ong5, D. Wadhwa6, S.J. Hotte7, G. Lo8, B. Tran9, A. Azad10, L. Wood11, J.R. Gingerich12, S. North13, C.V. Pezaro14, D. Ruether15, S.S. Sridhar16, M. Annala17, J. Bacon2, A.W. Wyatt2
  • 1Medical Oncology, BC Cancer - Vancouver Centre, V5Z 4E6 - Vancouver/CA
  • 2Urologic Sciences, University of British Columbia, V5Z1M9 - Vancouver/CA
  • 3Oncology, Saskatoon Cancer Centre University of Saskatchewan, S7N 4H4 - Saskatoon/CA
  • 4Medical Oncology, Jewish General Hospital McGill University, H3T 1E2 - Montreal/CA
  • 5Medical Oncology, Ottawa Hospital Cancer Centre, Ottawa/CA
  • 6Medical Oncology, BC Cancer - Kelowna Centre, Kelowna/CA
  • 7Medical Oncology, Juravinski Cancer Centre, L8V 5C2 - Hamilton/CA
  • 8Medical Oncology, Durham Regional Cancer Centre, Oshawa/CA
  • 9Medical Oncology, Peter MacCallum Cancer Centre, Melbourne/AU
  • 10Medical Oncology, Monash Health, Melbourne/AU
  • 11Medical Oncology, QEII Health Sciences Centre, Halifax/CA
  • 12Medical Oncology, CancerCare Manitoba, Winnipeg/CA
  • 13Medical Oncology, University of Alberta Cross Cancer Institute, T6G 1Z2 - Edmonton/CA
  • 14Oncology, Eastern Health, 3128 - Box Hill/AU
  • 15Medical Oncology, Tom Baker Cancer Centre, T2N 4N2 - Calgary/CA
  • 16Medical Oncology, Princess Margaret Hospital, M5G 2M9 - Toronto/CA
  • 17Department Of Urologic Sciences, Vancouver Prostate Centre-Vancouver General Hospital, V6H 3Z6 - Vancouver/CA

Abstract

Background

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.

Methods

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).

Results

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
CBR (%)82860.16
PSA50 (%)56600.68
OR (%)1112>0.90
SD > 12 weeks (%)62460.15
Median TTPP (m)7.44.80.73 (0.42-1.29)0.28
Median TTP (m)5.34.10.86 (.53-1.40)0.56
Median OS (m)NR15.50.56 (0.25-1.22)0.14

Conclusions

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

NCT02254785.

Legal entity responsible for the study

Kim N. Chi and BC Cancer.

Funding

Sanofi Genzyme, Prostate Cancer Canada Movember Disxcovery Grant, Canadian Institutes of Health Research Project Grant, Terry Fox Research Institute Program Project Grant.

Editorial Acknowledgement

Disclosure

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.