As this issue of Clinical Cancer Research goes to press, Vical, Inc., a pharmaceutical company developing an intralesional gene therapy for melanoma, Allovectin-7, announced its decision to discontinue development following negative results in a phase III trial (1). This story highlights the sea change that has occurred in therapy for metastatic melanoma. The phase III pivotal trial, which launched in 2006 (NCT00395070), compared Allovectin-7 to standard therapy—dacarbazine or temozolomide (2). The pivotal trial followed a phase II study in which an 11.8% response rate was observed, with durability for responding patients, yet a median time to progression of 1.6 months (3). These results, which were at that time sufficient to launch a pivotal trial in an era defined by negative phase III trials, contrast sharply with the 48% response rate for vemurafenib and 52% for dabrafenib in pivotal trials, with progression-free survivals of 5.3 and 5.1 months, respectively (4). Allovectin-7 represented a novel therapy with modest activity that might have received U.S. Food and Drug Administration approval a decade ago on the basis of durable responses alone, but in the wake of new drug approvals, expectations about therapy for melanoma have changed dramatically. We can only hope for such a sea change in other solid tumors. This edition of CCR Focus highlights the progress in our molecular understanding of melanoma, discusses the new agents that have raised the bar on efficacy, and reviews the challenges facing the field in combining the new strategies. With Guest Editors Keith Flaherty and Patricia LoRusso, the articles in this CCR Focus section discuss new molecular targets in melanoma, targeted therapy, the new immune checkpoint inhibitors, and adoptive cell transfer immunotherapy. As with every edition of CCR Focus, we hope to inform those interested but not expert in the field and to challenge those working in the field.
Susan E. Bates
Deputy Editor, CCR Focus
National Cancer Institute
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