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BackgroundBevacizumab 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 methodsPatients 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.ResultsPatients (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).ConclusionsAdjuvant 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 InformationISRCTN 81261306; EudraCT Number: 2006-005505-64

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.

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Aim: This study aims to determine the incidence of all immune-mediated adverse events (IMAEs) with a focus on hypophysitis in patients with metastatic melanoma receiving immune checkpoint inhibitors (ICI). Methods: 51 patients with metastatic melanoma who received immune checkpoint inhibitors (ipilimumab, pembrolizumab and nivolumab) in Ninewells Hospital, Dundee between 2014 and 2018 were identified. Patient demographic data and outcomes were recorded retrospectively. Results: A total of 6 patients (11.7%) developed hypophysitis, while 15 patients (29.4%) developed IMAEs. A significant improvement in overall survival (p = 0.03) and progression-free survival (p = 0.041) was seen in patients who developed IMAEs compared with those who did not. Conclusion: This study demonstrates a high rate of hypophysitis in melanoma patients receiving ipilimumab. Careful monitoring of symptoms is crucial to detect and appropriately manage IMAEs.