A randomized, double-blind phase II study of pembrolizumab versus placebo in patients with head and neck cancers at high risk for recurrence or low-volume residual disease: The PATHWay Study.

Abstract

TPS6095 Background: Head and neck squamous cell carcinoma (HNSCC) is a major medical problem worldwide. While some patients may be cured with a combination of surgery, radiation, and systemic therapies, a significant percentage of patients will have recurrent and incurable disease. Despite our epidemiologic understanding of which patients are likely to recur, there are no consolidative therapies that have been shown to improve outcomes in this high-risk population. Pembrolizumab is a PD-1 inhibitor that has shown significant single agent activity in recurrent/metastatic HNSCC after treatment with other systemic therapies. While drug development of pembrolizumab is ongoing in Phase III studies in the 2nd and 1stline recurrent/metastatic disease settings, the ultimately the biggest potential impact based on patient volume and survival will potentially be in the curative intent setting. This randomized study is intended to explore the incorporation of pembrolizumab into the treatment of patients with locally advanced HNSCC at high risk for recurrence. Methods: Eligible patients must have HNSCC, completed therapy with definitive intent, and have an estimated risk of recurrence ≥40-50% (including tumors with extensive lymphadenopathy, extracervical lymphadenopathy, indeterminate residual local or distant mass after treatment, non-responders to induction chemotherapy, incomplete definitive therapy, receipt of salvage therapies, or oligometastatic disease treated definitively). Patients will be randomized to 1 year of either pembrolizumab 200 mg or placebo, administered intravenously day 1 of each 3-week cycle. The primary hypothesis of the study is that the addition of pembrolizumab will improve the 2-year progression-free survival (PFS) rate, compared to placebo. A sample size of 90 (45 patients per treatment arm, assuming 10% loss of follow up in N = 100 patient trial) will achieve 92.7% power at alpha = 0.10 (one-sided) to detect a difference between 50% and 72.5% PFS at 2 years. Approximately 51 events are required to detect such a difference. Patient screening and enrollment are expected to begin spring 2017.