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Brief Research Report ARTICLE

Front. Med. | doi: 10.3389/fmed.2019.00257

Sequential treatment with targeted and immune checkpoint therapy in patients with BRAF positive metastatic melanoma: the importance of timing? Provisionally accepted The final, formatted version of the article will be published soon. Notify me

  • 1Universität zu Lübeck, Germany

Background: Immune checkpoint- and targeted therapy has dramatically improved the therapeutic landscape in the management of BRAF mutation positive metastatic melanoma. However, pending the results of clinical trials, not only is it currently unclear whether immune checkpoint- or targeted therapy should be commenced up front, but the optimal time for changing treatment, specifically to prevent resistance whilst maintaining disease control, is unknown.
Methods: We retrospectively identified eleven patients with BRAF V600 mutated metastatic melanoma who commenced targeted therapy between 11/2012 and 12/2017 in our centre. In 5 cases the decision was made to “electively” switch to immune checkpoint therapy (elective group) following the development of a complete or partial response. In the remaining 6 cases the initial “reactive” switch was necessitated by disease progression or the development of intolerable side-effects (reactive group).
Results: Overall, the elective cohort had a more favourable course in terms of overall survival (1003 vs 827 days), and 80% of the patients remain alive, in contrast to 17 % of the patients in the reactive group. However, it should be borne in mind that multiple switches due to disease progression were undertaken and this undoubtedly also impacted upon overall survival.
Conclusion: Elective switching from targeted to immune checkpoint therapy was associated with a better outcome in terms of survival, at least in everyday clinical practice. It remains unclear whether the choice of initial therapy confers a long–term survival and disease-control advantage and this should be addressed in prospective studies.

Keywords: Melanoma, Targetted therapies, sequential treatment, Immunothearpy, Immune check inhibitor (ICI)

Received: 23 Jul 2019; Accepted: 25 Oct 2019.

Copyright: © 2019 Graetz, Zillikens, Langan and Terheyden. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Ewan A. Langan, Universität zu Lübeck, Lübeck, 23562, Schleswig-Holstein, Germany, ewan.langan@uksh.de