Protocol 012 Investigators (2020). Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. The Lancet Respiratory Medicine.

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.

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This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. With an age standardised incidence rate of 0.63 per 100 000 population, hypopharynx cancers account for a small proportion of the head and neck cancer workload in the UK, and thus suffer from the lack of high level evidence. This paper discusses the evidence base pertaining to the management of hypopharyngeal cancer and provides recommendations on management for this group of patients receiving cancer care.Recommendations• Cross-sectional imaging with computed tomography of the head, neck and chest is necessary for all patients; magnetic resonance imaging of the primary site is useful particularly in advanced disease; and computed tomography and positron emission tomography to look for distant disease. (R)• Careful evaluation of the upper and lower extents of the disease is necessary, which may require contrast swallow or computed tomography and positron emission tomography imaging. (R)• Formal rigid endoscopic assessment under general anaesthetic should be performed. (R)• Nutritional status should be proactively managed. (R)• Full and unbiased discussion of treatment options should take place to allow informed patient choice. (G)• Early stage disease can be treated equally effectively with surgery or radiotherapy. (R)• Endoscopic resection can be considered for early well localised lesions. (R)• Bulky advanced tumours require circumferential or non-circumferential resection with wide margins to account for submucosal spread. (R)• Offer primary surgical treatment in the setting of a compromised larynx or significant dysphagia. (R)• Midline lesions require bilateral neck dissections. (R)• Consider management of silent nodal areas usually not addressed for other primary sites. (G)• Reconstruction needs to be individualised to the patients’ needs and based on the experience of the unit with different reconstructive techniques. (G)• Consider tumour bulk reduction with induction chemotherapy prior to definitive radiotherapy. (R)• Consider intensity modulated radiation therapy where possible to limit the consequences of wide field irradiation to a large volume. (R)• Use concomitant chemotherapy in patients who are fit enough and consider epidermal growth factor receptor blockers for those who are less fit. (R)

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