Abiraterone acetate (AA) followed by randomization to dasatinib (D) or sunitinib malate (S) in metastatic castrate resistant prostate cancer (mCRPC)

Date

09 Oct 2016

Session

Genitourinary tumours, prostate

Presenters

Eleni Efstathiou

Citation

Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372

Authors

E. Efstathiou1, A. Tsikkinis2, S. Wen1, E. Li Ning Tapia1, A. Hoang1, A. Aparicio1, S. Tu1, G. Rangel1, P. Troncoso1, P. Corn1, J. Araujo1, C. Logothetis1

Author affiliations

  • 1 Genitourinary Medical Oncology, MD Anderson Cancer Center, 77030-3721 - Houston/US
  • 2 Genitourinary Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
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Background

Src and Vegf, targeted by D and S respectively, have been implicated in CRPC progression. Moreover the unmet need for predictive markers has become pressing. We conducted a study to determine if the addition of either agents could prolong time to progression (TTP) on AA and to test a prespecified molecular signature.

Methods

This is a phase II study of AA in bone mCRPC patients randomized upon progression to combination with D or S, comparing the two treatment strategy. Endpoints include PFS, safety, survival, assessment of aprespecified signaling signature in pts with benefit vs primary resistance to AA (progression ≤ 4 months). Pts had pretreatment bone biopsy. Tumor Markers included, Androgen Receptor-N terminal (AR-N), AR-C terminal (AR-C), CYP17, Ki67, GR, ERG, Ki67 (%), pSrc, vegf, DNA repair genes by IHC and steroids by LCMS.

Results

Study (03/2011-02/2015) accrued 179 bone mCRPC pts and median follow up 27ms (9-57). Medians: Age, 68 ys (range 45-87), PS ECOG 1 (range 0-1) baseline PSA 20.6 (range 0.5-1655). 27 (16%) pts have visceral mets, 40 (22%) prior chemo. Diagnostic Gleason Score was ≥8 in 71%. Upon progression 128/179 pts were randomized: 64 to D (AD) and 64 to S (AS). Of these 61 crossed over and 30 are still on treatment. Fifty Five pts had primary resistance to AA. Thirteen pts discontinued due to adverse events (2 AA, 6AD and 5 AS) Median (CI 95%) TTP and Overall Survival (OS) for the cohort are 12.85 (11.08, 14.98 ) and 26.26 ( 23.21, 31.93 ) ms respectively. There is no difference for drug sequence. On multivariate analysis, primary resistance to AA (p

Conclusions

D or S do not improve AA efficacy or overcome primary resistance. Validation of prespecified androgen signaling signature predictive of AA response is planned in a multi-institutional study.

Clinical trial identification

NCT01254864

Legal entity responsible for the study

MD Anderson Cancer Center

Funding

Janssen

Disclosure

E. Efstathiou: research support, ad board honoraria; Janssen, Astellas, Sanofi, Medivation, Takeda.

C. Logothetis: Research: BMS, Medivation, Sanofi, Astellas, Janssen. Advisory boards: Astellas, AstraZeneca, Janssen, Sanofi, Bayer, Medivation, Clovis, Oncology, Churchill Pharmaceuticals.

All other authors have declared no conflicts of interest.

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