707TiP Postoperative adjuvant radiochemotherapy (aRCH) with cisplatin versus aRCH with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma: The ADRISK trial

Abstract

PD-1 immune checkpoint inhibitors have been approved for treatment of head and neck squamous cell carcinoma (HNSCC) in recurrent/metastatic settings as they significantly improve patients’ overall survival (OS). The next step is to explore the efficacy of immune checkpoint inhibitors in the curative setting, especially in patients with locoregional, pathologically intermediate and high-risk HNSCC which recur frequently despite adjuvant cisplatin-based radiochemotherapy (aRCH). Based on this rationale, we have developed the ADRISK trial to investigate the addition of pembrolizumab to standard aRCH in the treatment of patients with locally advanced intermediate- and high-risk HNSCC. Given the unmet need for reducing high rates of relapse in this patient group by improved adjuvant treatment, we expect that ADRISK will provide new insights into treatment and might demonstrate the ability of pembrolizumab to improve survival. ADRISK is a prospective, multicenter, randomized controlled phase II trial within the German Interdisciplinary Study Group of German Cancer Society. Patients with primary resectable stage III and IV HNSCC of the oral cavity, oropharynx, hypopharynx and larynx with pathologic high (R1, extracapsular nodal extension) or intermediate risk (R0 <5 mm; N≥2) after surgery who are eligible for cisplatin-based aRCH after surgery will receive either standard aRCH with cisplatin versus the same treatment + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months). The objectives are to show that addition of pembrolizumab to postoperative adjuvant cisplatin-based RCH improves event-free survival and OS compared with aRCH alone in locally advanced intermediate and high-risk HNSCC. To our knowledge, this is the only multicenter, randomized trial analyzing the addition of pembrolizumab to aRCH in this patient group without prior neoadjuvant treatment. Recruitment started in August 2018 and is ongoing. Until April 2022, 163 patients were registered for the trial and 157 patients were randomized. The planned sample size is 240 patients, the recruitment is estimated to be completed by July 2024 at the latest. NCT03480672. University of Leipzig.