Phase II clinical trial of neoadjuvant and adjuvant pembrolizumab in resectable local-regionally advanced head and neck squamous cell carcinoma
Abstract
Purpose: Patients with resected, local-regionally advanced, head and neck squamous cell carcinoma (HNSCC) have a 1-year, disease-free survival (DFS) of 65-69% despite adjuvant (chemo)radiotherapy. Neoadjuvant PD-1 immune checkpoint blockade (ICB) has demonstrated clinical activity, but biomarkers of response and effect on survival remain unclear. Experimental Design: Eligible patients had resectable squamous cell carcinoma of the oral cavity, larynx, hypopharynx or oropharynx (p16-negative) and clinical stage T3-T4 and/or two or more nodal metastases or clinical extracapsular nodal extension (ENE). Patients received neoadjuvant pembrolizumab 200mg 1-3 weeks prior to surgery, were stratified by absence (intermediate-risk) or presence (high-risk) of positive margins and/or ENE, and received adjuvant radiotherapy (60-66Gy) and concurrent pembrolizumab (q3 wks x 6 doses). Patients with high-risk HNSCC also received weekly, concurrent cisplatin (40mg/m2). Primary outcome was 1-year DFS. Secondary endpoints were 1-year OS and pathological response (PR). Safety was evaluated with CTCAE v5.0. Results: From February 2016 to October 2020, 92 patients enrolled. Median age was 59 years (range, 27 – 80), 30% were female, 86% had stage T3-T4 and 69% had ≥N2. At a median follow-up of 28 months, 1-year DFS was 97% (95% CI 71-90%) in the intermediate-risk group and 66% (95% CI 55-84%) in the high-risk group. Patients with a PR had significantly improved 1-year DFS relative to patients…
Read the paper
Related studies
- Challenges and opportunities with drug repurposing: finding strategies to find alternative uses of therapeutics
- Challenges in Chagas Disease Drug Development
- T Cell Specificity: A Great Challenge in Chagas Disease
- Benznidazole treatment leads to DNA damage in Trypanosoma cruzi and the persistence of rare widely dispersed non-replicative amastigotes in mice
- Rapid Molecular Detection of Terbinafine-resistant Dermatophytes
- Identifying novel drugs with new modes of action for neglected tropical fungal skin diseases (fungal skinNTDs) using an Open Source Drug discovery approach
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.