Optimal sequencing of new androgen-receptor targeted agents (ART) abiraterone and enzalutamide with docetaxel (D) and cabazitaxel (C) is unknown. In this large retrospective cohort of mCRPC patients, we evaluated the impact of 3 different sequences: D -> C-> ART (group 1), or D -> ART -> C (group 2), or ART -> D -> C (group 3)
Records of 560 consecutive mCRPC patients were retrospectively collected in 31 centres in 7 European countries from Jan 2011 to Jan 2016. Disease history and clinical characteristics at initiation of each therapy were collected. PSA response ≥ 50%, radiological or clinical progression-free survival (PFS) and overall survival (OS) with each treatment sequence were evaluated.
At sequence initiation, patient characteristics were similar between the 3 sequences: median age was 67 years, 95% were ECOG 0-1, 59% had high disease volume, 42.6% had pain and 8% had visceral metastases. Median number of D cycles was 6 in the 3 groups. Median numbers of C cycles were 7, 6 and 5 in groups 1, 2 and 3 respectively. Median duration of follow-up was 33.7, 31.1, and 23.7 months in groups 1, 2 and 3. Main results are provided in the table.
|Sequence||PSA response ≥50% / Radiological or clinical PFS*||OS from Treatment 1*|
|Treatment 1||Treatment 2||Treatment 3|
|D- > C- > ART (n = 129)||61% / 11.5||61% / 11.0||37% / 12.4||37.3 [32.4; 45.2]|
|D- > ART- > C (n = 390)||63% / 11.9||39% / 9.0||38% / 11.3||36.0 [33.4; 39.7]|
|ART- > D- > C (n = 41)||60% / 7.4||42% / 6.9||31% / 8.9||30.1 [24.3; 52.7]|
|p value||0.92 / |
PSA responses were generally similar for each treatment line in the 3 groups. No significant difference in OS was observed between the 3 sequences in this retrospective cohort. D showed a longer radiological or clinical PFS when given in first line. The activity of C was not influenced by ART. Sequencing should be based on individual disease characteristics and patients' status and preference.
Clinical trial identification
Legal entity responsible for the study
Sanofi and Janssen
A. Angelergues: Consulting fee Sanofi Travel for meeting Astellas and Janssen.
O. Caffo: Speakers bureaus: Astellas, Janssen, Sanofi, Bayer.
S. Le Moulec: Nonremunerative positions of influence (eg, officer, board member, trustee, or public spokesperson): Sanofi, Roche, BMS, Merck.
A. Guillot: Board Pfizer.
D. Spaeth: Consulting fees (or other payment): Sanofi and Janssen.
P. Beuzeboc: Consulting fees (or pther payment): Sanofi, Astellas, Janssen, Bayer, Amgen.
J-C. Eymard: Consulting fees : Sanofi, Novartis, Pfizer, Janssen Astellas.
A. Flechon: Consulting fees (or other payment): Sanofi, Astellas, Ipsen, Janssen, Ferring, Bayer.
J. Alexandre: Consulting fees (or other payment): Roche, Pharmamar, Novartis.
S. Oudard: Consulting fees (or other payment): Sanofi, Bayer, Astellas, Janssen.
All other authors have declared no conflicts of interest.