Treatment beyond progression

BRAF targets in melanoma. Biological mechanisms, resistance, and drug discovery. Cancer drug discovery and development. Volume 82. Ed. Ryan J. Sullivan. Springer (2015)


Selected patients develop progression at isolated disease sites while being treated with BRAF inhibitors which can be managed with local therapies (surgery, stereotactic radiosurgery). A retrospective analysis suggests that continuation of BRAF inhibitor therapy following local treatment for a solitary site of progression may be beneficial in this group of patients [46]. Patients in the initial phase I trial who continued vemurafenib following local therapy had a further progression-free interval of 3.6 months with a median OS which had not been reached at 6 month follow up. By contrast, patients who discontinued vemurafenib had a median overall survival of only 1.4 months. This finding may be a surrogate for the pace of disease progression (e.g. BRAF inhibitors are discontinued when there is obvious, rapid progression) or may be a genuine effect of continuing therapy.

Additionally, there have been case reports of objective responses occurring with re-treatment following a treatment-free interval. Two patients who developed disease progression (on vemurafenib and dabrafenib, respectively) had a treatmentfree interval of 8 and 4 months [47]. Upon BRAF inhibitor rechallenge, both patients experienced dramatic regression in their melanoma (qualifying as mixed response and partial response by RECIST criteria). This strategy can be considered in selected patients.

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