Abstract 1421P
Background
The PEACE-1 trial demonstrated improved overall survival (OS) in de novo mCSPC patients treated with a combination of androgen deprivation therapy, docetaxel, and abiraterone (AA) plus prednisone. Prostate cancers with neuroendocrine differentiation (NEPC) are rare. Most trials exclude de novo NEPC, thus their standard of care remains uncertain. As NEPC was allowed in PEACE-1, we aimed to assess the effect of AA in NEPC and those with very high-risk factors (Gleason >8, liver metastases).
Methods
We reviewed local pathological reports (biopsy site, WHO pathological classification, chromogranin A (CgA), and synaptophysin immunohistochemical [NE IHC] staining) from patients randomized in PEACE-1. Baseline characteristics were compared between patients with and without NEPC. Prognostic value of NEPC and high-risk factors on radiographic progression-free survival (rPFS) and OS was studied by Cox models. Predictive value of these factors was assessed by adding an interaction between AA and each factor.
Results
Pathological reports were available for 1087 out of 1172 patients (97%). NE IHC was only locally performed in 18% of patients and NEPC diagnosed in 2.4%. Among reports with NE IHC, 13.2% (n =26) of patients had an adenocarcinoma with NE differentiation and 0.5% had pure NEPC. PSA at baseline was significantly lower in NEPC than in adenocarcinoma without NEPC (p=0.003). Baseline disease burden, visceral metastasis, and Gleason scores were similar in both group. NE features predicted for both rPFS (median 1.6 vs 2.9 years; HR 2.2, 95%CI [1.4-3.5], p=0.0004) and OS (median 2.4 vs 5.1 years; HR 2.7, 95%CI [1.7-4.4], p<0.0001). The effect of AA could not be reliably assessed due to an insufficient number of NEPC. The Gleason score (6-7 vs 8 vs 9-10) had no impact on the effect of AA on OS (p=0.73). Among patients with liver metastases (n=36), AA improved rPFS (HR 0.3, 99.9%CI [0.08-1.00], p=0.06) and tended to improve OS (HR 0.5, 95.1%CI [0.23-1.10], p=0.22).
Conclusions
Only a very small minority of men with mCSPC are diagnosed with NEPC by their local pathologist, questioning the need for more systemic IHC in these men. AA significantly improves rPFS in patients with liver metastases.
Clinical trial identification
GETUG-AFU 21, UC-0160/1105, EudraCT 2012-000142-35.
Editorial acknowledgement
Legal entity responsible for the study
Unicancer.
Funding
Janssen Pharmaceutical NV, Ipsen, Sanofi, French Academic Institution Financial support (PHRC).
Disclosure
A. Bernard-Tessier: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Other: Orion, Bayer; Non-Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Advisory Board: Novartis. M. Cancel: Financial Interests, Personal, Invited Speaker: Janssen, Sanofi, BMS; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Invited Speaker: Janssen. B. Tombal: Financial Interests, Personal, Advisory Board: Astellas, Bayer, Amgen, Janssen, Sanofi, Myovant, Novartis (AAA), Pfizer, MSD, AstraZeneca; Financial Interests, Personal, Invited Speaker: Astellas, Amgen, Ferring; Financial Interests, Personal, Expert Testimony: Astellas; Non-Financial Interests, Invited Speaker, Past President: European Organisation of Research and Treatment of Cancer (EORTC); Non-Financial Interests, Invited Speaker, Education in the field of Oncology: ISSECAM. G. Roubaud: Financial Interests, Other: Astellas, Ipsen, Sanofi, Janssen. J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas Pharma, AstraZeneca, Bayer, Johnson & Johnson, MSD Oncology, Novartis (AAA), Roche, Sanofi; Financial Interests, Institutional, Invited Speaker: Janssen-Cilag International NV, Lilly, S.A, MedImmune, Novartis Farmacéutica, S.A, Sanofi-Aventis, S.A. A. Flechon: Financial Interests, Personal, Expert Testimony: Sanofi, Astra Zeneca, Astellas, Janssen, AAA, Bayer; Financial Interests, Personal, Invited Speaker: Novartis. R.S. McDermott: Financial Interests, Personal, Advisory Board: Pfizer, Amgen, BMS, Bayer, Janssen, Clovis; Financial Interests, Personal, Invited Speaker: MSD, Ipsen, Astellas; Financial Interests, Institutional, Invited Speaker: MSD, Clovis, BMS, Regeneron, Bayer, Astellas. S. Supiot: Financial Interests, Other: Bayer, Janssen, Astellas, Ipsen, Sanofi; Financial Interests, Principal Investigator: AstraZeneca, Janssen, Astellas. D.R. Berthold: Financial Interests, Institutional, Invited Speaker: Astellas, Janssen; Financial Interests, Institutional, Advisory Board: MSD, Ipsen, Bayer, BMS, Roche. G. Kacso: Financial Interests, Invited Speaker: Astellas, AstraZeneca, J&J, Novartis, Sanofi, Merck; Financial Interests, Institutional, Invited Speaker: Amethyst; Financial Interests, Personal and Institutional, Project Lead: AstraZeneca; Non-Financial Interests, Principal Investigator: Nanobiotix, Unicancer, Astella, AZ, Janssen, MSD. G. Gravis Mescam: Financial Interests, Institutional, Advisory Board: AAA, Alliance Merck-Pfizer, Astellas, BMS, Janssen, Pfizer, ipsen, alliance Merck Pfizer; Financial Interests, Institutional, Invited Speaker: AAA, Amgen, Astellas, BMS, Janssen, MSD, Pfizer, Sanofi, Ipsen, AstraZeneca, BMS; Financial Interests, Institutional, Funding: Janssen; Non-Financial Interests, Principal Investigator: Ipsen, BMS, Merck. F. Calabrò: Financial Interests, Advisory Board: BMS, MSD, AstraZeneca, Ipsen, Merck, Pfizer; Financial Interests, Principal Investigator: Parexel, AstraZeneca, BMS, Syneos, MSD, PRA, J&J, Janssen, Icon, Roche, Eisai, Bayer. J.F. Berdah: Financial Interests, Personal, Invited Speaker: Astellas, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Janssen Cilag. C. Hennequin: Financial Interests, Other: Astellas, Janssen, Ipsen, Bouchara, Bayer. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion. All other authors have declared no conflicts of interest.