Moving the goal posts in prostate cancer trials

Abstract

In The Lancet Oncology, Fred Saad and colleagues 1 Saad F Fizazi K Jinga V et al. for the ELM-PC 4 investigatorsOrteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial. Lancet Oncol. 2015; (published online Feb 18.)http://dx.doi.org/10.1016/S1470-2045(15)70027-6 PubMed Google Scholar present final data from ELM-PC 4, a phase 3 trial of orteronel plus prednisone versus placebo plus prednisone in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer. Orteronel was developed to inhibit CYP17-mediated secondary androgen production via selective blocking of 17,20-lyase. Although abiraterone acetate has similar biological effects and is already approved for metastatic castration-resistant prostate cancer, orteronel represented another candidate androgen biosynthesis inhibitor. This study 1 Saad F Fizazi K Jinga V et al. for the ELM-PC 4 investigatorsOrteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial. Lancet Oncol. 2015; (published online Feb 18.)http://dx.doi.org/10.1016/S1470-2045(15)70027-6 PubMed Google Scholar enrolled 1560 patients, randomly assigning 781 patients to receive orteronel plus prednisone and 779 to receive placebo plus prednisone. The co-primary endpoints were radiographic progression-free survival and overall survival. Despite a benefit in radiographic progression-free survival (median 13·8 months with orteronel plus prednisone vs 8·7 months with placebo plus prednisone; hazard ratio [HR] 0·71; 95% CI 0·63–0·80; p<0·0001) as well as improvements in PSA response and circulating tumour cells, orteronel plus prednisone did not improve overall survival (median 31·4 months with orteronel plus prednisone vs 29·5 months with placebo plus prednisone; HR 0·92; 95% CI 0·79–1·08; p=0·31). Of note, EML-PC 5, a study in docetaxel-treated metastatic castration-resistant prostate cancer, also failed to show an overall survival advantage for oteronel and prednisone versus placebo and prednisone, despite a benefit in radiographic progression-free survival. 2 Fizazi K Jones R Oudard S et al. Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5. J Clin Oncol. 2015; (published online Jan 26.)https://doi.org/10.1200/JCO.2014.56.5119 Crossref Scopus (108) Google Scholar Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trialIn chemotherapy-naive patients with metastatic castration-resistant prostate cancer, radiographic progression-free survival was prolonged with orteronel plus prednisone versus placebo plus prednisone. However, no improvement was noted in the other primary endpoint, overall survival. Orteronel plus prednisone was associated with increased toxic effects compared with placebo plus prednisone. On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer. Full-Text PDF