Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial.

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours.

Genetic Susceptibility in Head and Neck Squamous Cell Carcinoma in a Spanish Population.

Despite classical environmental risk factors like tobacco, alcohol or viral infection, not all individuals develop head and neck cancer. Therefore, identification of the genetic susceptibility produced by single nucleotide polymorphisms (SNPs) is an important task. A total of 296 human papillomavirus negative head and neck cancer (HNC) patients (126 laryngeal, 100 pharyngeal and 70 oral cavity) were included in the study, involving 29 candidate SNPs in genes within important carcinogenic pathways (oncogenesis and tumour suppression, DNA repair, inflammation, oxidation and apoptosis). Genotyping was performed using TaqMan probes or restriction fragment length assays in peripheral blood DNA. In addition, 259 paired controls were also evaluated with the same risk factors for each specific location. Nine SNPs in DNA repair (ERCC1 rs11615, ERCC2 rs13181), inflammatory (IL2 rs2069762, IL6 rs1800795), oxidative (NFE2L2 rs13035806 and rs2706110) and apoptotic genes (TP53 rs1042522, MDM2 rs2279744, BCL2 rs2279115) were differently associated with HNSCC susceptibility by location. Some of these SNPs were not described before in this tumour type. In conclusion, we describe several SNPs associated with HNC in a Spanish population.

Phase II study of panitumumab and paclitaxel as first-line treatment in recurrent or metastatic head and neck cancer. TTCC-2009-03/VECTITAX study.

OBJECTIVE: To evaluate the activity and safety profile of panitumumab in combination with paclitaxel in patients with recurrent or metastatic SCCHN. MATERIALS AND METHODS: The VECTITAX phase II, open-label, multicenter study included patients with confirmed metastatic and/or recurrent SCCHN deemed to be untreatable by surgery or radiotherapy and ECOG PS=0-1. All patients received paclitaxel (80mg/m2/week) and panitumumab (6mg/kg/2weeks) until disease progression or unacceptable toxicity. EQ-5D-3L andvisual analogic scale (VAS) were used to evaluate impact on quality of life (QoL). RESULTS: The study included 40 patients (ITT population): (median age: 61 years; 87% male). Previous treatment: 29 patients (73%) had undergone surgery, 34 (85%) had received prior radiotherapy and 23 (58%) prior systemic treatment for locally advanced disease. Confirmed response was observed in 19 patients (48%) which was a complete response in 15% of patients. Stable disease was observed in 11 patients (28%). Disease control rate was 75%. Median progression-free survival was 7.5 months (95%CI: 4.9-8.3) and median overall survival 9.9 months (95%CI: 7.9-16.3). Most frequent grade 3-4 adverse events were skin rash (25%); asthenia (17%); neurotoxicity (15%); hypomagnesemia (10%); neutropenia (10%). Permanent discontinuation of panitumumab or paclitaxel due to adverse events was required in 10 (25%) and 13 patients (33%), respectively. There was one toxic death due to febrile neutropenia. Patient-reported QoL was preserved with no decline of median VAS scores. CONCLUSION: Panitumumab and paclitaxel is an active combination, providing promising outcomes with preservation of the QoL and a favorable safety profile. (EudraCT: 2010-018898-37; NCT01264328).