PracticeUpdate: Dermatology & Rheumatology

2016 TOP STORIES IN DERMATOLOGY 4

Dr Jane Grant-Kels onmelanoma

Jane Grant-Kels MD is Professor and founding Chair of the Department of Dermatology at the University of Connecticut Health Center and Medical School, and an Advisory Board Member of PracticeUpdate Dermatology. She specialises in cutaneous oncology and pigmented lesions of the skin.

T here continues to be incredible excitement in the melanoma field due to a constant flow of advances and discoveries. I have chosen three to share with you. In the area of therapy, last year’s approval of ipilimumab as adjuvant therapy for stage  III melanoma opened the door to a new era in melanoma treatment. This approval was based on the pivotal study by Eggermont et al ( Lancet Oncol 2015;16:522-530). For a long time, there has been an unmet need for an approved adjuvant therapy for stage III melanoma patients besides interferon, which is only marginally helpful and very toxic. This multicentre and international group performed a double-blind phase 3 trial with 951 patients with stage III cutaneous melanoma who had not received previous therapy except surgery. Patients were randomised to receive intravenous ipilimumab (10 mg/kg) or saline every 3 weeks for four doses and then every 3 months for 3 years. The group who received the adjuvant ipilimumab had significantly improved recurrence-free survival (median survival was 26.1 months, and 3-year survival was 46.5%) versus the placebo group (median survival was 17.1 months, and 3-year survival was 34.8%). Adverse events were immune-related and resulted in discontinuation of therapy by 52% of the patients receiving active therapy and 5 deaths. Despite the toxicity of ipilimumab, the adjuvant therapy clearly improved recurrence-free survival. The dosage used of 10 mg/kg is higher than the approved dose of 3 mg/kg that is used in patients with stage IV disease. Further investigation on dosing is ongoing in the ECOG 1609 (NCT 01274338) study that is comparing 1 year of ipilimumab at 10 mg/kg versus 3 mg/ kg versus high-dose interferon. So, stay tuned. More information to come to help our stage III melanoma patients!

Another major development in treating melanoma is our new understanding of the regulatory pathways and immune checkpoints in the adaptive immune response to melanoma. A wonderful review from the Moffitt Cancer Center (United States) details how inhibitors of these checkpoints can be utilised to treat melanoma ( Semin Oncol 2015;42:363-377). Blockades by an antibody to CTLA-4 or an antibody to PD-1 have now been shown to be successful strategies either alone or in combination in melanoma patients. Other emerging checkpoint proteins (BTLA, VISTA, CD 160, LAG3, TIM3, CD244, and others) are also being investigated as potential targets for inhibition. Finally, a recent paper by Kaisaki et al presents data that may transform the way we diagnose and follow our melanoma patients ( PLoS One 2016;11:e0162809). Imagine if we could draw the blood of our melanoma patients to see how they have responded to therapy. This study suggests that might not be too far in the future. This group studied circulating tumour DNA of melanoma patients and lung cancer patients. Solid tumours often release DNA into the circulation and therefore the blood could be a source for a “liquid” biopsy. The 21 known melanoma patients were studied retrospectively to confirmwhether themutations in the primary melanoma would also be detectable in the circulating tumour DNA. Blood samples were drawn within 1 year of biopsy or before treatment. Circulating DNA showed good concordance with the primary melanoma mutations. Of note was that circulating DNA sequenced after targeted melanoma therapy demonstrated that in 9 out of 10 patients, the mutations were no longer found. This suggests that circulating DNA could be a way to follow therapeutic responses in our melanoma patients!

A recent paper by Kaisaki et al

presents data that may transform the way we diagnose and follow our melanoma

patients. Imagine if we could draw the blood of our

melanoma patients to see how they have responded to therapy. This study suggests that might not be too far in the future.

PRACTICEUPDATE RHEUMATOLOGY & DERMATOLOGY