Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy

Abstract

Background: Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC. Patients and methods: Immunotherapy-naïve patients with confirmed PD-L1-high tumour cell expression (defined as patients with 25% of tumour cells expressing PD-L1 [TC 25%] using the VENTANA PD-L1 [SP263] Assay) received durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months. The primary end-point was objective response rate; secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: Among evaluable patients (n Z 111), objective response rate was 16.2% (95% confidence interval [CI], 9.9e24.4); 29.4% (95% CI, 15.1e47.5) for human papillomavirus (HPV)-positive patients and 10.9% (95% CI, 4.5e21.3) for HPV-negative patients. Median PFS and OS for treated patients (n Z 112) was 2.1 months (95% CI, 1.9e3.7) and 7.1 months (95% CI, 4.9e9.9); PFS and OS at 12 months were 14.6% (95% CI, 8.5e22.1) and 33.6% (95% CI, 24.8e42.7). Treatment-related adverse events were 57.1% (any grade) and 8.0% (grade 3); none led to death. At data cut-off, 24.1% of patients remained on treatment or in follow-up. Conclusion: Durvalumab demonstrated antitumour activity with acceptable safety in PD-L1high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in firstand second-line settings. In an ad hoc analysis, HPV-positive patients had a numerically higher response rate and survival than HPV-negative patients.

Impact of PD‐L1 expression and human papillomavirus status in anti‐PD1/PDL1 immunotherapy for head and neck squamous cell carcinoma—Systematic review and meta‐analysis

“…With respect to inhibiting the PD‐1 pathway, this difference remains controversial as our study did not identify any statistically significant difference in ORR, SD, PD, or OS when patients were stratified according to HPV status. Previous studies have identified a response benefit for HPV positive patients, while conflicting results were observed in other studies . Our analysis has demonstrated that the difference in ORR is approaching statistical significance ( P = .06), thus, it remains an interesting front for future investigators to explore if HPV‐positive patients do indeed receive enhanced treatment benefits with PD1 inhibitors.…”

“…Clinical trials of R/M HNSCC patients receiving monotherapy PD‐1/L1 blockade have demonstrated variable outcomes among patients stratified by PD‐L1 expression and HPV status . However, these trials have utilized a variety of methodologies for determining PD‐L1 and HPV expression, and further reported various cutoff points for determining PD‐L1 “positivity.” These inconsistencies are largely owing to the absence of a standardized method for quantifying PD‐L1 expression and determining an appropriate cutoff level to dichotomize patients.…”

Review of emerging biomarkers in head and neck squamous cell carcinoma in the era of immunotherapy and targeted therapy

“…In addition to PD‐L1 expression, microsatellite instability (MSI) predicted response to PD‐L1 inhibitors in HNSCC . HPV status was predictive of improved response to durvalumab . Furthermore, a higher number of some subtypes of tumor‐infiltrating lymphocytes (TILs), such as PD‐1 + TIM‐3 + CD8 + TILs and PD‐1 + LAG‐3 + CD8 + TILs, and higher tumor mutation burden (TMB) and CD8 + TILs, all predicted improved response to anti‐PD‐1 or anti‐PD‐L1 therapies …”

Immune checkpoint inhibitors for head and neck squamous cell carcinoma: Current landscape and future directions

“…Durvalumab and atezolizumab are two anti‐PD‐L1 monoclonal antibodies (Table ). In phase I/II studies, both antibodies demonstrated results comparable with studies of nivolumab and pembrolizumab.…”