Patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with high PD-L1 expression who have progressed on platinum-based chemotherapy mounted a strong response to the anti-PD-L1 immunotherapy durvalumab, according to findings presented during ESMO 2017, the Annual Congress of the European Society for Medical Oncology, in Madrid, Spain.
Reports that programmed cell death 1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC, among other tumour types, prompted Dan P. Zandberg, Hematology/Oncology, University of Maryland Greenebaum Comprehensive Cancer Center in Baltimore, Maryland, USA, to investigate durvalumab as monotherapy in patients with R/M HNSCC in the global, single-arm, phase II HAWK study (NCT02207530).
HAWK enrolled immunotherapy-naïve adult patients with high PD-L1 expression, defined as ≥25% staining of tumour cells using the VENTANA SP263 Assay, who had progression or recurrence during or after 1 platinum-based regimen for R/M HNSCC. Durvalumab at 10 mg/kg was administered intravenously to 112 patients for up to 12 months or until progression, the initiation of another anticancer therapy, consent withdrawal, or unacceptable toxicity occurred. The recruited patients, from 12 countries, had a median age of 60 years, 71.4% were male, 34.3% were human papillomavirus (HPV)-positive, and 61.6% of patients were either current or former smokers.
The primary endpoint of the study was objective response rate (ORR) by blinded independent central review according to RECIST v1.1. Progression-free survival (PFS) and overall survival (OS) were secondary endpoints.
Durvalumab shows promise in poor prognosis patients with recurrent/metastatic HNSCC and limited therapeutic options
At data cut-off (DCO) on 31 March 2017 the median duration of treatment was 3.45 months and median follow-up was 6.13 months. Among the 111 patients with evaluable data, the ORR was 16.2% (95% confidence interval [CI], 9.9–24.4). Of the 18 responding patients, 10 (55%) had an ongoing response at DCO.
The disease control rate at 24 weeks (patients with a complete response or partial response plus those with stable disease at 24 weeks) was 23.4%.
In the overall cohort, median PFS was 2.1 months (95% CI, 1.9–3.7) median OS was 7.1 months (95% CI, 4.9–9.9) and the 12-month survival rate was 33.6% (95% CI, 24.8–42.7).
Higher response rates were observed in HPV-positive patients with HNSCC
When the response was evaluated in an exploratory analysis according to HPV status, patients who were positive for HPV demonstrated an ORR of 29.4%, compared with ORR 10.8% in those who were negative for HPV.
Durvalumab demonstrated a manageable safety profile consistent with previous reports. The incidence of grade ≥3 treatment-related adverse events (AEs) was 8.0%. Only 1 patient discontinued durvalumab because of a treatment-related AE. There were no deaths due to a treatment-related AE.
The authors concluded that promising antitumour activity was demonstrated with durvalumab, together with an acceptable safety profile, in patients with R/M HNSCC and high PD-L1 expression. These data support the potential use of durvalumab in this patient population.
Phase III studies of durvalumab with or without tremelimumab (anti-CTLA-4) in recurrent or metastatic HNSCC are currently ongoing (EAGLE NCT02369874 and KESTREL NCT02551159).
The study was supported by AstraZeneca.
1042O – Zandberg D, et al. Durvalumab for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): preliminary results from a single-arm, phase 2 study.