Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

Complete response in a melanoma patient treated with imatinib.

BACKGROUND: Imatinib therapy has been successful in gastrointestinal stromal tumours containing mutation of the KIT gene. However, there are few reported cases of successful imatinib therapy in patients with melanoma containing KIT gene mutation or c-kit protein expression. METHODS AND RESULTS: A 52-year-old man developed metastatic melanoma from a primary melanoma in the left side of the nasopharynx. The tumour was positive for c-kit protein, and there was a KIT mutation in exon 11. He was treated with imatinib. A follow-up scan one year later showed a complete response. Treatment targeting the biological characteristics of melanoma proved successful in this patient.

Head and neck cancer.

Head and neck cancer is traditionally thought of as being a disease associated with alcohol and tobacco abuse and deprivation. It was the fourth most common cancer in males in Scotland in 2000 and just over 1,000 cases were diagnosed in 2007. As smoking becomes less prevalent, a fall in the incidence of head and neck cancer could be anticipated; however, increasing evidence of other aetiological factors contributing to the diagnosis of head and neck cancer, particularly oropharyngeal cancer in non-smoking, little-drinking populations, is impacting on that perception. This review will aim to look at current aetiological factors for head and neck cancer, along with current therapeutic modalities in treatment of this disease.

Biological therapy of salivary duct carcinoma.

BACKGROUND: The incidence of human epidermal growth factor receptor 2 positivity in salivary duct carcinoma ranges from 25 to 100 per cent and is associated with a poor outcome. Salivary duct carcinoma has significant pathological similarities to ductal carcinoma of the breast. METHODS AND RESULTS: A 49-year-old man developed lung and liver metastasis a few months after surgery and adjuvant radiotherapy for salivary duct carcinoma of the parotid gland. There was no response to palliative chemotherapy with doxorubicin. We followed the biological model of breast cancer, whereby two-thirds of human epidermal growth factor receptor 2 positive patients respond to a combination of docetaxel and human epidermal growth factor receptor 2 blocker (trastuzumab). A durable, complete response was achieved with this combination. A rationalised treatment approach targeting the biological characteristics of salivary duct carcinoma had proven successful.