Combination Therapy With Demcizumab in Nonsquamous Lung Cancer
Adding demcizumab to first-line carboplatin and pemetrexed treatment did not seem to improve outcomes in patients with metastatic nonsquamous non–small cell lung cancer (NSCLC). These results from the DENALI trial were presented by Brett Hughes, BSc (Med), MBBS (Hon), FRACP, a medical oncologist at the Royal Brisbane & Woman’s Hospital and the University of Queensland, Brisbane, Australia, at the 2017 American Association for Cancer Research–National Cancer Institute–European Organisation for Research and Treatment of Cancer (AACR-NCI-EORTC) International Conference on Molecular Targets and Cancer Therapeutics (Abstract A084) in Philadelphia.
Demcizumab is a humanized anti–Delta-like ligand 4 antibody. This ligand activates the Notch pathway, which has been found to be key in the survival of cancer stem cells.
A total of 82 patients with NSCLC were randomized to one of three treatment groups. One group was given carboplatin, pemetrexed, and placebo (CPP). The other two groups received carboplatin, premetrexed, and either one or two 70-day truncated courses of demcizumab (CPD).
A total of 52% of the CPP group and 28% of the pooled CPD groups responded to treatment, with a clinical benefit rate of 92% versus 79%, respectively. The median progression-free survival for the placebo group was 8.7 months compared with 5.5 months in the pooled demcizumab arms. As for overall survival, the interim median for the CPP group had not been reached compared with 15.5 months for the pooled CPD groups. The most common reported side effects with demcizumab were nausea, fatigue, constipation, anemia, and hypertension.