Reinhard Dummer, Prof. Dr. med. Stv. Klinikdirektor Universitätsspital Zürich, Dermatologische Klinik Zürich

Targeted Combination Immunotherapy Improved Survival in Stage III Melanoma Interview with:

Reinhard Dummer, Prof. Dr. med. Stv. Klinikdirektor Universitätsspital Zürich, Dermatologische Klinik Zürich

Prof. Dummer

Reinhard Dummer, Prof. Dr. med.
Stv. Klinikdirektor
Universitätsspital Zürich, Dermatologische Klinik
Zürich What is the background for this study?

Response: Based on molecular biology analysis, a substantial proportion of melanomas are driven by mutations of BRAF resulting in an ongoing growth activating signal. Based on the key role of BRAF several multiple kinase molecules have been developed in order to target this crucial pathway. These medications have shown to improve progression free survival and overall survival in advanced metastatic melanoma.

Because there is a tendency for improved outcome in patients with low tumor burden, combined targeted therapy using Dabrafenib and Trametinib have been investigated in the adjuvant (after complete surgical resection) setting in stage III melanoma. And the 5 year data are now available in the New England Journal of Medicine. What are the main findings?

Response: The main findings are a clinical meaningful improvement of progression free survival and a very stable long-term effect on overall survival without long-term toxicities. What should readers take away from your report?

Response: Targeted therapy is considered to be very efficient for a limited time and therefore long-term benefit was considered to be limited. However in this clinical trial we document that there is a consistent long-term improvement of a overall survival despite treatment discontinuation after 1 year. This suggest that a low tumor burden might be associated with an improved long-term outcome if targeted therapy is used for BRAF mutated melanoma. What recommendations do you have for future research as a result of this work?

Response: There is a urgent need for biomarkers that identify the early progresses during adjuvant therapy. Potentially these patients would profit from immunotherapy alone or from combination using targeted therapy and immunotherapy. The treatment duration of this adjuvant therapy was 12 month, however we do not know whether this is the optimal treatment duration. Early biomarker results suggest that in a subgroup longer treatment durations might be necessary.

In other patients a shorter treatment could be sufficient. Is there anything else you would like to add?

Response: The disclosures are attached to the article.

I would like to thank the patient who have participated, the steering committee of this clinical trial, all the recruiting centers and the sponsor Novartis for the support.


New England Journal of Medicine

Source Reference: Dummer R, et al “Five-year analysis of adjuvant dabrafenib plus trametinib in stage III melanoma” N Engl J Med 2020; DOI: 10.1056/NEJMoa2005493.

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Last Updated on September 3, 2020 by Marie Benz MD FAAD