Poor Phase III Results Reported for Orteronel, Necitumumab Trials

Orteronel and necitumumab fail to improve survival outcomes in specific populations of prostate cancer and non-small-cell lung cancer patients

medwireNews: Poor phase III results for two trials published in The Lancet Oncology mark the end of the line for orteronel plus prednisone as a treatment for chemotherapy-naive men with castration-resistant, metastatic prostate cancer, and for necitumumab in non-squamous, non-small-cell lung cancer (NSCLC).

The double-blind ELM-PC 4 trial showed a significant improvement in radiographical progression-free survival for the 781 men randomly assigned to receive prednisone alongside orteronel versus the 779 men given prednisone plus placebo, at a median of 13.8 versus 8.7 months and a hazard ratio of 0.71.

However, the partially selective inhibitor of CYP 17,20-lyase did not significantly improve overall survival.

This “might have been due to both the tolerability and safety profile of orteronel as well as the availability of new alternative therapies”, report Fred Saad, from Centre Hospitalier de l’Université de Montréal in Quebec, Canada, and co-authors who say that orteronel will not undergo further development in this patient population.

Specifically, orteronel was associated with an increased rate of grade 3 or more severe adverse events including elevated lipase and amylase, fatigue, and pulmonary embolism, with 46% of orteronel-treated patients reporting serious adverse events compared with 38% of controls.

The open-label INSPIRE trial of patients who had not previously received chemotherapy for stage IV non-squamous NSCLC also failed to show a significant improvement in overall survival for the epidermal growth factor receptor (EGFR) monoclonal antibody, necitumumab.

Median overall survival was a comparable 11.3 months for the 315 patients given necitumumab plus pemetrexed and cisplatin and 11.5 months for the patients given pemetrexed and cisplatin only. Nor was there a significant benefit for necitumumab with regard to progression-free survival, objective response or disease control.

And compared with pemetrexed and cisplatin alone, the necitumumab regimen was associated with a higher rate of grade 3 or more severe adverse events (72 vs 59%) and serious adverse events (51 vs 41%).

Luis Paz-Ares, from Instituto de Biomedicina de Sevilla-IBIS in Spain, and team note that patients with a high immunohistochemistry H-score for tumour EGFR protein expression did not have significantly better overall or progression-free survival than those with low scores.

“Unless future studies identify potentially useful predictive biomarkers, necitumumab is unlikely to provide benefit in this patient population when combined with pemetrexed and cisplatin”, they conclude.


Saad F, Fizazi K, Jinga V, et al. Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial. Lancet Oncol 2015; Published online 17 February. DOI: dx.doi.org/10.1016/S1470-2045(15)70027-6

Paz-Ares L, Mezger J, Ciuleanu TE, et al. Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study. Lancet Oncol 2015; Published online 17 February. DOI: dx.doi.org/10.1016/S1470-2045(15)70046-X

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