In a single-center phase I/II trial reported in The Lancet Oncology, Douglas Adkins, MD, and colleagues found that the recommended phase II dose of ramucirumab combined with pembrolizumab was active in the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Douglas Adkins, MD
Study Details
Forty patients (n = 3 in phase I, 37 in phase II) were enrolled in the trial at Washington University School of Medicine in St. Louis between June 2019 and February 2021. In phase I, patients received ramucirumab at a starting dose of 10 mg/kg and pembrolizumab at 200 mg on day 1 of each 21-day cycle. The primary outcome measure of phase II was objective response in the per protocol population; it was hypothesized that the objective response rate would be ≥ 32% (with a null hypothesis of < 13%).
Objective Responses
No ramucirumab dose-limiting toxicities were observed in phase I. The recommended phase II dose of ramucirumab was 10 mg/kg used in combination with pembrolizumab at 200 mg on day 1 of each 21-day cycle, with treatment continued until disease progression or unacceptable toxicity.
Median follow-up for patients in phase II was 14.8 months (interquartile range [IQR] = 4.9–31.0 months). Among 33 evaluable patients (those with at least one response assessment), objective response was observed in 18 (55%, 95% confidence interval [CI] = 38%–70%), including confirmed complete response in 11 (33%). Stable disease was observed in an additional eight patients (24%). Median duration of response was 14.0 months (IQR = 7.8–28.7 months).
Among all 37 patients in phase II who received at least one dose of study treatment, median progression-free survival was 5.5 months (95% CI = 3.2–13.3 months), and median overall survival was 14.6 months (95% CI = 7.5–29.6 months).
KEY POINTS
- Ramucirumab plus pembrolizumab produced objective response in 55% of patients.
- Median response duration was 14.0 months (interquartile range = 7.8–28.7 months).
Adverse Events
Grade 3 adverse events occurred in 31 (84%), grade 4 adverse events occurred in 10 (27%), and grade 5 adverse events occurred in 5 (14%) patients in phase II; the most common grade ≥ 3 adverse events were dysphagia (38%), lung infection (30%), decreased lymphocyte count (27%), hypophosphatemia (24%), and hypertension (22%). Drug-related serious adverse events included infusion reactions, myocardial infarction, hypertension, and dehydration. A total of 12 patients (32%) required a dose hold or discontinuation of either ramucirumab (n = 11) or pembrolizumab (n = 1). No treatment-related deaths were reported.
The investigators concluded, “Ramucirumab and pembrolizumab were safe to administer to patients with recurrent or metastatic HNSCC, and the objective response rate with this combination as first-line treatment for recurrent or metastatic HNSCC was favorable. Further studies of ramucirumab and pembrolizumab in patients with recurrent or metastatic HNSCC are warranted.”
Dr. Adkins, of the Division of Medical Oncology, Washington University School of Medicine, St. Louis, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Joseph Sanchez Foundation and Lilly. For full disclosures of the study authors, visit thelancet.com.
