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New Adjuvant Regimens and Molecular Targets Emerge as Prime Research Focus

Anita T. Shaffer
Published Online: Thursday, November 14, 2013
Dr. Vernon K. Sondak

Vernon K. Sondak, MD

Adjuvant therapy for patients with advanced melanoma and the optimal use of molecular testing are among the most pressing issues facing oncologists who treat patients diagnosed with the disease.

Both subjects were tackled during the Update for Clinicians on Diagnosis and Treatment of Melanoma and Other Cutaneous Malignancies, a one-day conference that Physicians’ Education Resource (PER) hosted at the Moffitt Cancer Center in Tampa, Florida, on September 28.

In presentations and interviews, leading researchers discussed treatment and diagnostic implications of new agents that the FDA has approved during the past two years as well as consensus recommendations published recently by the Society for Immunotherapy of Cancer (SITC),1 whose members have been pioneers in the field.

As with other malignancies, an increased understanding of the molecular drivers of melanoma has offered another dimension to therapy decisions beyond traditional clinical and histopathologic factors (Figure).

Importance of Surgery

Kaufman et al noted that the prognosis for patients with advanced disease remains grim. “Survival decreases to 50% for patients with localized lymphnode metastases (stage III), and metastatic disease (stage IV) historically had a median survival of 8-9 months and a 3-year overall survival rate less than 15%,” the authors said.1

Figure. Moffitt Melanoma Analysis

Moffitt Melanoma AnalysisD

Source: Magliocco AM. The Future--Molecular Subtyping of Melanoma. Presented at: Update for Clinicians on Diagnosis and treatment of Melanoma and Other Cutaneous Malignancies; September 28, 2013; Tampa, FL. Reprinted with permission.

Before 2011, adjuvant treatment for patients with melanoma was limited to interferon alfa-2b (IFN-α2b) while patients with metastatic disease received dacarbazine or high-dose interleukin-2, the researchers observed. Now, the options have expanded, but many questions remain about how to integrate the new therapies. The SITC paper sets forth algorithms for stages II-IV disease.

“We’re very excited to see these new guidelines come out,” said Vernon K. Sondak, MD, a coauthor of the SITC paper and one of the conference course directors. Sondak chairs the Department of Cutaneous Oncology and serves as the director of Surgical Education at Moffitt Cancer Center

Sondak said it is particularly noteworthy that the multidisciplinary panel of experts who developed the guidelines incorporated the role of surgery at all stages. “These were mostly nonsurgeons but they stress the importance of surgery in the treatment of melanoma even into stage IV disease,” said Sondak in an interview. “If you can resect all of the disease and render the patient disease-free, that is a key first step.”

Although many patients with advanced disease are not candidates for surgery, the guidelines stress that option “shouldn’t be forgotten after the decision is made to treat with immune therapy because it is not unusual that the patient will have a good response to immune therapy in some areas, but maybe there is one tumor that doesn’t go away or even one that starts to grow.”

“That is an important message simply because it doesn’t get made very often,” said Sondak.

Immunotherapy in Adjuvant Settings

The best opportunity for improving outcomes for patients with advanced melanoma arises after surgical resection in patients at high risk for melanoma recurrence and mortality, and research indicates that the optimal approach at that juncture would be the use of immunotherapy, according to Ahmad A. Tarhini, MD, PhD, in a presentation that focused primarily on patients with surgically resected stage III and stage IV disease.

Dr. Ahmad A. Tarhini

Ahmad A. Tarhini, MD, PhD

Tarhini is an associate professor in the Department of Medicine and Translational Science at the University of Pittsburgh School of Medicine in Pennsylvania and one of the coauthors of the SITC consensus statement on immunotherapies.1

Analyses of tumor antigen- specific T-cell profiles suggest that the impact of immunotherapy may be greatest after surgical resection of high-risk melanoma and before the body develops immune tolerance of the cancer cells, leading to cancer recurrence, said Tarhini.

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