Phase II Durvalumab Trial in Resistant Head and Neck Cancer
Posted: Tuesday, January 15, 2019
Among patients with PD-L1–high (≥ 25%) expression, those who had human papillomavirus (HPV)-positive disease seemed to respond better to durvalumab monotherapy in the setting of recurrent or metastatic head and neck squamous cell carcinoma. These results from a single-arm, phase II study, which were published in the European Journal of Cancer, support the ongoing evaluation of this agent in phase III trials in both first-line and second-line settings.
The study, also known as the HAWK trial, included 111 evaluable immunotherapy-naive patients from North American and European institutions. All of them had failed to respond to a platinum-based chemotherapeutic regimen in the recurrent or metastatic setting, according to Dan P. Zandberg, MD, of Hillman Cancer Center, University of Pittsburgh Medical Center, and colleagues. In fact, most of the study patients had failed to respond to cetuximab as well.
The anti–PD-L1 monoclonal antibody durvalumab was given at 10 mg/kg intravenously every 2 weeks for up to 12 months. “PD-1 and its ligand PD-L1 are frequently upregulated in head and neck squamous cell carcinoma,” noted the team.
The overall objective response rate was 16.2%. An ad hoc analysis showed that for patients with HPV-positive and -negative disease, the overall objective response rate was 29.4% and 10.9%, respectively. As for toxicity, were 57.1% of patients had any-grade treatment-related adverse events and 8.0% had grade ≥ 3 treatment-related events. Nearly one-quarter of patients remained on treatment or in follow-up at data cutoff.
The authors concluded that the antitumor activity and safety profile of this agent supports its ongoing study in phase III trials in first- and second-line settings. These studies are EAGLE (ClinicalTrials.gov identifier NCT02369874) and KESTREL (NCT02551159), which are evaluating the agent with or without the monoclonal antibody tremelimumab.
Disclosure: The study authors’ disclosure information may be found at ejcancer.com.