Early Results With Dual Inhibition of VEGFR2 and PD-1 in Advanced Lung Cancer
Posted: Thursday, August 8, 2019
In a multicenter, multicohort, nonrandomized, open-label, phase Ia/b trial, Roy S Herbst, MD, PhD, of Yale Cancer Center, and colleagues set out to assess the safety and preliminary antitumor activity of the VEGFR2 antagonist ramucirumab combined with the PD-1 antagonist pembrolizumab in patients previously treated for lung, gastroesophageal, or urothelial cancers. According to the investigators, this dual therapy showed no unexpected safety findings and favorable antitumor activity. Their results were reported in The Lancet-Oncology.
A total of 92 patients with histologically confirmed and previously treated advanced non–small cell lung cancer (n = 27), gastric or gastroesophageal junction adenocarcinoma (n = 41), or urothelial carcinoma (n = 24) whose disease had progressed on previous therapy were enrolled and treated. Adverse events occurred in 75 patients (82%), with 33 patients (36%) experiencing grade 1 or 2 fatigue. Most serious treatment-related adverse events were of grade 3 or lower severity, and few patients discontinued treatment due to treatment-related adverse events.
At data cutoff, in the combined cohorts, 76 patients (83%) had disease progression, 66 (72%) of whom had died. A total of 51 evaluable patients (61%) had a decrease in target lesion size. Confirmed objective responses were reported in 14 patients (15%): One patient had a complete response and 13 had a partial response. Although patients who tested positive for PD-L1 in the gastrointestinal and urothelial cohorts appeared to have higher antitumor activity, those in the lung cancer cohort responded to treatment regardless of PD-L1 status.
“Efficacy endpoints in our study showed favorable outcomes compared with immune checkpoint inhibitor monotherapy in other studies,” the authors stated. “The combination of ramucirumab with pembrolizumab could be explored in future trials either with or without chemotherapy, especially in tumors for which single-agent checkpoint inhibitors have failed to show benefit over chemotherapy.”
Disclosure: The study authors’ disclosure information may be found at thelancet.com.