Since 2015, docetaxel chemotherapy, combined with ADT, is considered the standard of care in fit men with metastatic hormone-naive prostate cancer (mHNPC), based on data from three phase III trials (GETUG-AFU 15, CHAARTED, and STAMPEDE). No data are currently available regarding activity of treatments used beyond progression after upfront ADT and docetaxel.
We retrospectively collected data from patients (pts) participating in the GETUG-AFU 15 phase III trial concerning treatments received beyond progression for castration-resistant disease (CRPC) in both arms (ADT and ADT + docetaxel) including treatment efficacy (measured by a PSA decline, physician assessment of clinical benefit, and time to events), and toxicity (NCI-CTC grading).
245 pts received at least one anticancer treatment at CRPC progression. The treatments most frequently used and their efficacy are detailed in the Table. Toxicity was mild, with only rare grade 3-4 events (17%). Median overall survival measured after the onset of CRPC was respectively 2.29 years (IC95% [1.84-2.59]) and 1.97 years (IC95% [1.64-2.73]) in the ADT and ADT + D arms.
Efficacy of treatments used for CRPC
|Treatment used for CRPC (N = 245 pts)||PSA response (ADT vs ADT + D)||Symptomatic response (ADT vs ADT + D)||Median PFS Months (95%CI) (ADT vs ADT + D)|
|First treatment for CRPC||Docetaxel based chemotherapy (N = 104)||23/68 (34%) vs 3/18 (17%)||16/55 (29%) vs 5/17 (29%)||7.0 (4.3-9.2) vs 4.1 (1.3-5.0)|
|Bicalutamide (N = 61)||12/28 (43%) vs 4/24 (17%)||0/12 (0%) vs 3/21 (14%)||5.1 (3.2-11.7 ) vs 3.2 (2.1-6.9 )|
|Abiraterone or Enzalutamide (N = 13)||1/2 vs 6/9||1/2 vs 1/4|
|Second treatment for CRPC||Docetaxel based chemotherapy (N = 49)||12/17 (71%) vs 0/9 (0%)||5/17 (29%) vs 5/12 (42%)||6.0 (4.2-8.5) vs 2.5 (0.9-6.2)|
|Abiraterone or Enzalutamide (N = 34)||5/7 (71%) vs 4/7 (57%)||4/8 vs 2/11||6.0 (1.0-9.1 ) vs 5.6 (1.0- )|
|Mitoxantrone (N = 17)||0/8 vs 0/4||1/6 vs 2/7|
|Platin based chemotherapy (N = 15)||0/6 vs 1/2||4/10 vs 0/1|
In this retrospective analysis, anticancer activity was suggested with androgen receptor axis-targeted agents even in patients with metastatic prostate cancer treated upfront with ADT + docetaxel. We observed that docetaxel rechallenge had rather limited activity in this setting.
Clinical trial identification
NCT00104715; release date: 2013 Februray (Lancet Oncol)
Legal entity responsible for the study
French Health Ministry and Institut National du Cancer (PHRC), Sanofi-Aventis, AstraZeneca, and Amgen
F. Joly: Roche, Pfizer, Novartis, Sanofi, Jansen, Astellas.
M. Soulié: Amgen, Astellas, Astra Zeneca, Ferring, Glaxo Smith K, Ipsen, Jansen, Keocyt, Novartis, Pierre Fabre, Sanofi, Takeda, Zambon.
B. Laguerre: Pfizer, Novartis, Jansen.
K. Fizazi: Participation to advisory boards and honorarium : Sanofi, Janssen, Astellas.
All other authors have declared no conflicts of interest.