1. The benefit of combining docetaxel to androgen deprivation therapy in localized and metastatic castration-sensitive prostate cancer as predicted by ERG status: An analysis of two GETUG phase III trials
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Philippe Vielh, Remy Delva, Frederic Rolland, Frank Priou, Loic Mourey, Anne Chauchereau, Stéphane Culine, Ivan Krakowski, Stéphanie Foulon, Gwenaelle Gravis, Nadine Houede, François Lesaunier, Jean-Marc Ferrero, Karim Fizazi, Muriel Habibian, Alexandra Carmel, Christine Theodore, Laura Faivre, Zahira Merabet, and Shanna Rajpar
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Oncology ,Cancer Research ,medicine.medical_specialty ,Phase iii trials ,genetic structures ,business.industry ,030232 urology & nephrology ,medicine.disease ,Castration-sensitive prostate cancer ,Androgen deprivation therapy ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Docetaxel ,Internal medicine ,medicine ,030211 gastroenterology & hepatology ,business ,Erg ,medicine.drug - Abstract
5012 Background: Combining docetaxel to androgen deprivation therapy (ADT) improves survival in metastatic castration-sensitive prostate cancer (CSPC) (Vale C, Lancet Oncol 2016; 17: 243-56) and it also improves relapse-free survival (RFS) in high-risk localized CSPC (Fizazi K, Lancet Oncol 2015; 16: 787-94). However it is unlikely that all patients (pts) derive a benefit from docetaxel treatment and identifying predictive biomarkers remains a major unmet need. A subset of prostate cancers contains TMPRSS2-ERG gene fusions leading to ERG overexpression. Methods: Pre-treatment prostate core biopsies were collected from 255/413 pts and 79/385 pts enrolled respectively in the GETUG 12 and GETUG 15 (Gravis G, Eur Urol 2016; 70: 256-62) phase 3 trials testing early docetaxel in high-risk localized and metastatic CSPC. ERG, PTEN, Ki67 and Rb expression was assessed using immunohistochemistry. RFS curves were compared using the Logrank test. Results: The median age was 63 years (46-77) and 62 years (49-76) in GETUG 12 and GETUG 15. ERG staining was positive in 88/191 (46%) and 33/79 (42%) pts with available tissue, respectively. In GETUG 12, docetaxel-based chemotherapy was associated with improved RFS in pts with ERG+ expression (HR = 0.55 [0.29-1.03]; 6-year RFS : 80% ADT+docetaxel vs 68% ADT alone), but not in pts with ERG- (HR = 1.10 [0.66-1.85]; 6-year RFS 55% ADT+docetaxel vs 60% ADT alone), interaction test: p = 0.02. Similar findings were observed in GETUG 15, which was used as a validation set: the median RFS was 10.7 (6.5-14.3) and 18.8 (9.8-41) months in pts with ERG+ cancers receiving ADT alone and ADT+docetaxel, and 10.6 (4.8-25.3) and 13.2 (9.4-24) months in pts with ERG- cancers. In contrast, no difference in patient outcome by docetaxel treatment was observed by PTEN, Ki67 and Rb expression. Conclusions: Docetaxel-related benefit in men with CSPC is predicted by ERG expression. This biomarker may help better select pts for docetaxel treatment.
- Published
- 2017
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