A phase 1a/b trial (NCT02443324) reports that ramucirumab in conjunction with pembrolizumab is effective in patients with previously treated advanced non-small cell lung cancer (NSCLC), gastroesophageal cancer, or urothelial carcinomas.
Ramucirumab, a monoclonal antibody, blocks vascular endothelial growth factor receptor 2 (VEGFR2), which allows cancer cells to grow and metastasize. Pembrolizumab is also a monoclonal antibody, but it works by blocking programmed cell death protein-1 (PD-1), in turn preventing the binding and activation of programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2), thereby allowing T cells to fight cancer.
For this study, published in The Lancet Oncology, researchers enrolled 92 patients with histologically confirmed gastric or gastroesophageal junction adenocarcinoma, NSCLC, or urothelial carcinoma. Patients were eligible for the trial if their disease had progressed after receiving one or two lines of therapy for gastric or gastroesophageal cancer or one to three lines of therapy for NSCLC or urothelial cancer. For all tumor types, disease progression on therapy that included platinum, fluoropyrimidine, or both (for those with gastric or gastroesophageal cancer) also was required for eligibility. Patients were given 200 mg pembrolizumab and 8 mg/kg ramucirumab, administered intravenously on days 1 and 8 in the first 21-day treatment cycle as a dose-limiting toxicity observation period, followed by an expansion phase.
After a median follow-up period of 32.8 months, objective response was achieved in 7% of patients with gastric or gastroesophageal cancer, 30% of patients with NSCLC, and 13% of patients with urothelial carcinoma.
Seventy-five of 92 patients experienced side effects, including fatigue of grade 1/2 severity in 36% of patients; hypertension (7%) and colitis (5%) were the most common grade 3/4 treatment-related events that occurred. For patients with gastric or gastroesophageal cancer, abdominal pain was the most common side effect of treatment, occurring in 7% of patients. Asthenia and myocardial infarction (7%) were the most common in patients with NSCLC. Urothelial carcinoma patients most commonly experienced colitis (8%). One treatment-related death occurred from pulmonary sepsis.
"Ramucirumab in combination with pembrolizumab showed a manageable safety profile with favorable antitumor activity in patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma, non-small cell lung cancer, and urothelial carcinoma," conclude the study authors, led by lead author Roy S Herbst MD, PhD, Ensign Professor of Medicine at Yale Cancer Center. "Our results contribute to the growing evidence that supports dual inhibition of the VEGF-VEGFR2 and PD-1–PD-L1 pathways. This combination could be further explored with or without chemotherapy, especially for patients with tumors for which single-agent checkpoint inhibitors have shown no additional benefit over chemotherapy."
For More Information
Clinicaltrials.gov (2019). A study of ramucirumab plus pembrolizumab in participants with gastric or GEJ adenocarcinoma, NSCLC, transitional cell carcinoma of the urothelium, or biliary tract cancer. NLM Identifier: NCT02443324.
Herbst RS, Arkenau HT, Santana-Davila R, et al (2019). Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a/b trial. Lancet Oncol. [Epub ahead of print] DOI:10.1016/S1470-2045(19)30458-9
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