Key clinical point: For patients with epidermal growth factor receptor–mutated non–small cell lung cancer (NSCLC), adding the vascular endothelial growth factor receptor 2 inhibitor ramucirumab to standard erlotinib therapy may extend progression-free survival.
Major finding: Patients treated with ramucirumab plus erlotinib had a longer progression-free survival than patients treated with erlotinib alone (19.4 vs. 12.4 months).
Study details: A randomized, double-blind, placebo-controlled, phase 3 trial involving 449 patients with epidermal growth factor receptor–mutated non–small cell lung cancer.
Disclosures: The RELAY trial was funded by Eli Lilly. The investigators reported additional relationships with AstraZeneca, Bristol-Myers Squibb, Novartis, and others.
Nakagawa K et al. Lancet Oncol. 2019 Oct 4. doi: 10.1016/S1470-2045(19)30634-5.
The study by Nakagawa et al. suggests that epidermal growth factor receptor tyrosine kinase inhibitors may feasibly be combined with other drugs, but concerns remain about the infrequency of complete responses, which were uncommon in this trial, at 1%, and only slightly higher, at 7%, in a previous, similar trial that involved the addition of bevacizumab to erlotinib (Lancet Oncol. 2019 Apr 8. doi: 10.1016/S1470-2045(19)30035-X). A lack of complete responses may be caused by vascular endothelial growth factor inhibition, which reduces tumor burden, but also may increase risks of tumor invasion, metastases, hypoxia, and other malignant processes.
Hypothetically, multitargeted receptor tyrosine kinases, such as cabozantinib or foretinib, could counteract the above drawbacks, but this remains to be seen. In the meantime, investigators should aim to design trials based on preclinical data instead of empirical reasoning. Despite the complexity of the molecular pathophysiology involved, research is bringing us closer to a clear understanding of the network of relationships between pathways, which could ultimately enable effective use of available combinations.
Rafael Rosell, MD, PhD, and Carlos Pedraz-Valdunciel are with Germans Trias i Pujol Research Institute and Hospital and the Universitat Autónoma de Barcelona. Both authors declared no competing interests. Their remarks are adapted from an accompanying editorial (Lancet Oncol. 2019 Oct 4. doi: 10.1016/S1470-2045(19)30636-9).