Sequencing of Docetaxel (D) and Abiraterone Acetate (Aa) for Metastatic Castration-Resistant Prostate Cancer (Mcrpc)

Abstract

Aim: D and AA are approved as front-line treatments for mCRPC. Their optimal sequencing is as yet undefined. We retrospectively evaluated whether sequencing of AA and D has an effect on survival in mCRPC.Methods: We retrospectively identified mCRPC patients (pts) who received both D and AA at the Royal Marsden Hospital. Pts were divided into two groups, the first having received D followed by AA (D- > AA) and the second AA followed by D(AA- > D). Pts who received D in the non-castrate setting or enzalutamide prior to D or AA were excluded. Hormonal treatments or phase I/II investigational agents were allowed between D and AA. Cabazitaxel(C) was allowed either before or after the second part of treatment. Overall survival (OS) was defined as time from initiation of first treatment, D or AA, to death or last follow-up (LFU). Log-Rank testing was used to compare OS between the two groups and two-sided Pearson's Chi-Square and Student's t-test to compare categorical and continuous variables respectively.Results:⇓ Between 10/2004 and 06/2012 161 and 37 mCRPC pts were identified who received D- > AA and AA- > D respectively. Baseline mean values of prognostic parameters were comparable in the two groups: Hg was 11.9g/dl and 12.7g/dl (p = 0.04), LDH 195.2u/l and 203.6u/l(p = 0.5), ALP 252.1u/l and 156u/l(p = 0.1), albumin 35.2g/l and 36.9g/l(p = 0.06), PSA 786.3ng/ml and 118.7ng/ml (p = 0.7) –median(m)PSA 131ng/ml and 72ng/ml- in D- > AA and AA- > D group respectively. Similar proportion of pts received C in the two groups: 36 pts (22.4%) in D- > AA and 4 (10.8%) in AA- > D (p = 0.1). After a mFU of 2.7 years 18 pts (11.2%) in the D- > AA group were alive and 2 (5.4%) in the AA- > D group; mOS was 31.4 months (95%CI: 28.3-34.4) in D- > AA and 38.6months (95% CI:30.3-46.9) in AA- > D (p = 0.6). The difference was not statistically significant.Conclusions: This retrospective analysis did not identify a statistically significant difference in mOS between pts treated with D- > AA or AA- > D. Prospective studies to evaluate optimal treatment sequencing for mCRPC are warranted.Disclosure: Z. Zafeiriou: Employee at the time of manuscript preparation of the Institute of Cancer Research, Sutton, Surrey, UK, that has commercial interest in abiraterone. Z.Z has received grants from Hellenic Society of Medical Oncology; R. Ferraldeschi, A. Altavilla, S. Sideris, P. Rescigno, D. Bianchini, A. Smith, R. Perez Lopez, N. Mehra, P. Ravi, E. Grist and N. Tunariu: Employee at the time of manuscript preparation of the Institute of Cancer research, Sutton, Surrey, UK, that has commercial interest in abiraterone; A. Omlin: Employee at the time of manuscript preparation of the Institute of Cancer research, Sutton, Surrey, UK, that has commercial interest in abiraterone. Advisory role: Janssen as COI; C. Pezaro and D. Mukherji: Employee at the time of manuscript preparation of the Institute of Cancer research, Sutton, Surrey, UK, that has commercial interest in abiraterone. Has has received honoraria from Sanofi-Aventis and Janssen-Cilag; D. Lorente: Employed at the Institute of Cancer Research, which has a commercial interest in the development of abiraterone; J. Mateo: Employed at the Institute of Cancer Research when the abstract was created, which has a commercial interest in the development of this agent; G. Attard: GA is listed in the ICR co-inventors reward scheme for abiraterone acetate; J.S. de Bono: JSB has a consultant role with Johnson & Johnson, and received honoraria from Johnson & Johnson. Consultant and Chief Investigator of the Abiraterone Trial.