Current Approaches to Therapy—Case Studies in Nonmelanoma Cutaneous Malignancies
Today’s opening session began with a review by Dr. Sanjiv Agarwala of yesterday’s presentations and a preview of today’s sessions. The opening session was a review of current approaches to nonmelanoma cutaneous malignancies. Using a case-based approach with several patient cases, Dr. Karl Lewis discussed current approaches to treating locally advanced and metastatic basal-cell carcinoma (laBCC and mBCC). He highlighted the efficacy and safety of surgical approaches, topical therapy, and systemic therapy with vismodegib and sonidegib in treating laBCC and mBCC. Dr. Lewis reviewed the data from the ERIVANCE and STEVIE studies with vismodegib and the BOLT study with sonidegib, and showed a summary of the safety and efficacy of these agents in patients with laBCC and mBCC. Both agents are effective in clearing lesions and increasing progression-free survival in these patients. He stressed, however, that the long-term impact of these Hedgehog inhibitors on the natural history of mBCC is unknown, and that more information is needed about mechanisms of resistance to these agents, as well as development of agents against alternative SMO binding sites and molecular targets such as PI3K. Dr. Madeleine Duvic then discussed current therapy for cutaneous T-cell lymphoma, including current management guidelines for this heterogeneous group of skin cancers, but focusing on mycosis fungoides (MF) and Sezary syndrome (SS). Using a case-based approach, she showed the current treatment algorithm for MF based on the stage of disease and the presence of patch/plaque disease, including the safety and efficacy of skin-directed topical therapies (eg, bexarotene and PUVA), radiation therapy, and systemic targeted agents (eg, brentuximab, denileukin, vorinostat, and romidepsin), which are used in extensive and refractory disease. She followed a similar course in her discussion of current treatment of SS, including first-line combination immunotherapy and second-line targeted therapies with histone deacetylase (HDAC) inhibitors and emerging agents (eg, alemtuzumab). She concluded that treatment of MF and SS depends on the stage of disease, and that better combinations of topical and systemic therapies are needed for these cutaneous malignancies. Dr. Manisha Thakuria then presented a case-based discussion of current approaches to therapy of Merkel-cell carcinoma (MCC), a rare but aggressive malignancy with debatable optimal treatment. Using several typical case studies of patients with MCC, she highlighted the National Comprehensive Cancer Network (NCCN) guidelines for diagnosis and workup of MCC, particularly as it relates to imaging techniques and the need for sentinel lymph node biopsy. Dr. Thakuria then traced the NCCN algorithm for treating MCC with wide surgical excision and radiation therapy in lymph node–negative disease, as well as principles of radiation therapy and chemotherapy with carboplatin ± etoposide in metastatic disease. She cautioned that careful follow-up of MCC patients treated with any of these modalities is important due to the risk for recurrence, with 91% of recurrences occurring within 2 years of initial diagnosis. This session was followed by a vigorous question-and-answer session in which many attendees presented management challenges in their own patients for the panel to consider. Interestingly, melanoma experts weighed in on therapy for MCC, cutaneous T-cell lymphoma, and BCC, demonstrating the multidisciplinary nature of this meeting.