(UroToday.com) The 2022 European Society of Medical Oncology (ESMO) annual meeting featured a prostate cancer session, including a presentation by Dr. Alice Bernard-Tessier discussing the results of the PEACE-1 trial, specifically the effect of abiraterone-prednisone in metastatic castration-sensitive prostate cancer (mCSPC) with neuroendocrine and very high-risk features.
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 plus prednisone.1 Prostate cancers with neuroendocrine differentiation are rare. Most trials exclude de novo neuroendocrine differentiated prostate cancer, thus their standard of care remains uncertain. As neuroendocrine differentiated prostate cancer was allowed in PEACE-1, Dr. Bernard-Tessier and colleagues aimed to assess the effect of abiraterone in neuroendocrine differentiated prostate cancer and those with very high-risk factors (Gleason >8, liver metastases).
This study reviewed local pathological reports (biopsy site, WHO pathological classification, chromogranin A, and synaptophysin immunohistochemical staining) from patients randomized in PEACE-1. Baseline characteristics were compared between patients with and without neuroendocrine differentiated prostate cancer. Prognostic value of neuroendocrine differentiated prostate cancer 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 abiraterone and each factor.
Pathological reports were available for 1,087 out of 1,172 patients (93%). Synaptophysin immunohistochemical staining was only locally performed in 18% of patients and neuroendocrine differentiated prostate cancer diagnosed in 2.4%. Among reports with synaptophysin immunohistochemical staining, 14% of patients had an adenocarcinoma with neuroendocrine differentiation and 0.5% had pure neuroendocrine differentiated prostate cancer. PSA at baseline was significantly lower in neuroendocrine differentiated prostate cancer than in adenocarcinoma without neuroendocrine differentiated prostate cancer (4 ng/mL, IQR 2-13 vs 13 ng/mL IQR 3-62; p = 0.003). Baseline disease burden, visceral metastasis, and Gleason scores were similar in both group. Neuroendocrine 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 abiraterone could not be reliably assessed due to an insufficient number of neuroendocrine differentiated prostate cancer. The Gleason score (6-7 vs 8 vs 9-10) had no impact on the effect of abiraterone on OS (p = 0.73). Among patients with liver metastases (n=36), abiraterone 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).
Dr. Bernard-Tessier concluded her presentation discussing the results of the PEACE-1 trial, specifically the effect of abiraterone-prednisone in mCSPC with neuroendocrine and very high-risk features with the following take-home messages:
- Only a very small minority of men with mCSPC are diagnosed with neuroendocrine differentiated prostate cancer by their local pathologist, questioning the need for more systemic immunohistochemistry in these men
- Abiraterone significantly improves rPFS in patients with liver metastases.
Presented by: Alice Bernard-Tessier, MD, Oncology Dept., Institut Gustave Roussy, Villejuif, France
Co-Authors: M. Cancel2, B. Tombal3, G. Roubaud4, J. Carles Galceran5, A. Flechon6, R.S. McDermott7, S. Supiot8, D.R. Berthold9, R. Philippe10, G. Kacso11, G. Gravis Mescam12, F. Calabro'13, J.F. Berdah14, A. Hasbini15, F. Ricci16, C. Hennequin17, H. Ribault18, S. Foulon19, K. Fizazi20
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during 2022 European Society of Medical Oncology (ESMO) Annual Hybrid Meeting, Paris, FR, Fri, Sept 9 – Tues, Sept 13, 2022.
- Fizazi K, Foulon S, Carles J, Roubaud G, et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): A multicentre, open-label, randomized, phase 3 study with a 2 x 2 factorial design. Lancet. 2022 Apr 30;399(10336):1695-1707.
Related Content: Overall Survival Results of PEACE-1 a Phase 3 Trial in Men With De Novo Metastatic Castration-Sensitive Prostate Cancer (mCSPC) – Karim Fizazi