New Prescribing Options in Metastatic Melanoma | Page 5
Published Online: October 11, 2013
John A. Thompson, MD
For patients whose melanoma expresses mutation of BRAF by a Clinical Laboratory Improvement Amendments– approved laboratory assay, vemurafenib is added to the choices listed above, though the questions of ideal timing and sequencing have yet to be answered. Within the population with BRAF-mutant tumors, it might sometimes be appropriate to initiate systemic therapy with an immunotherapeutic agent (eg, ipilimumab, IL- 2) to potentially induce a long-term antitumor response. If progression of disease is documented and the timing of progression suggests that a delayed response to immunotherapy is unlikely (eg, continued progression of disease at 16 weeks after initiation of ipilimumab), immunotherapy can be discontinued and vemurafenib therapy started. In patients who present initially with symptomatic metastatic melanoma, who have a high bulk of metastatic disease and/or a rapid tempo of progression, there may not be enough time for induction of an effective immune response. In this situation, use of an agent specifically targeted at mutant BRAF (for example, vemurafenib) is clearly indicated because of the rapid onset of antitumor effect and the high response rate associated with BRAF inhibitors.
Although great progress has been made, most patients still experience disease progression despite therapy with the aforementioned newer agents, indicating a continued need for additional options. Clinical trials in melanoma include studies of cellular therapy with adoptive transfer of autologous, antigen-specific T cells; novel immune “check-point inhibitors” such as anti-PD-1 or anti-PDL1; lymphokines such as IL-15 or IL-21; antiangiogenic agents such as bevacizumab or anti-integrins; molecularly targeted agents such as inhibitors of MEK, RAS, or PI3 kinase; or combinations of the above. With new therapies
and new combinations being explored, the future is promising for treatment of patients with advanced or metastatic melanoma.
Author Affiliation: From Seattle Cancer Care Alliance, Seattle, WA.
Funding Source: The author wishes to acknowledge StemScientific, funded by Bristol-Myers Squibb, for providing writing and editorial support.
Author Disclosure: The author reports no relationship or financial interest with any entity that would pose a confl ict of interest with the subject matter of this article.
Authorship Information: Analysis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content; and supervision.
Address correspondence to: John A. Thompson, MD, Seattle Cancer Care Alliance, 825 Eastlake Ave East, G4-830, Seattle, WA 98109-1024. E-mail: firstname.lastname@example.org.
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