Multiple abstracts on melanoma and skin cancer were reviewed at the ASCO Annual Meeting, with a focus on new treatment approaches in non-melanoma skin cancers; here I will briefly summarize some of the reported new evidence and studies looking at non-melanoma skin cancers, particularly basal cell carcinoma and Merkel cell carcinoma.
Currently, there are no gold standards in the treatment of locally advanced basal cell carcinoma, but options have included surgery (which may have limited effects and can be both debilitating and disfiguring) and radiation therapy. Effective strategies for the management of metastatic basal cell carcinoma are also needed. The sonic hedgehog pathway is thought to be instrumental in the development of basal cell carcinoma, and SHH and PTCH1 are two members of the pathway that are thought to be implicated in the formation of basal cell carcinoma.
A recently explored treatment option is the oral smoothened inhibitor vismodegib, which has been looked at in the setting of locally advanced and metastatic basal cell carcinoma. In a phase II single-arm international trial entitled ERIVANCE (SHH4811g), 104 patients with advanced basal cell carcinoma (71 with locally advanced disease and 33 with metastatic disease) who were not candidates for surgery or radiation therapy were enrolled and received vismodegib at 150 mg daily, until disease progression or intolerability. It was reported that vismodegib had an overall response rate of 43% for locally advanced basal cell carcinoma and 30% for metastatic basal cell carcinoma. The median progression-free survival for both locally advanced and metastatic basal cell carcinoma was 9.5 months.
Recent advances in another non-melanoma skin cancer, Merkel cell carcinoma, were also reviewed. Merkel cell carcinoma is known to have aggressive clinical behaviors. Patients with immunodeficiencies (such as HIV/AIDS) and chronic lymphocytic leukemia, as well as organ transplant recipients, have an increased risk of this type of cancer. Current recommended treatments for Merkel cell carcinoma involve wide excision and radiation. Some experts may recommend adjuvant chemotherapy in the setting of positive lymph nodes, in select patients; however, current clinical practice guidelines for Merkel cell carcinoma are based on the scant available data and may be in a state of flux.
In a French Cooperative Group study that looked at the value of sentinel node biopsy for patients with Merkel cell carcinoma, 87 patients were assessed and it was found that there was a clear survival correlation with a sentinel node biopsy and also with the administration of radiation therapy. Adjuvant radiation therapy was delivered to the involved lymph node bed in 19 out of 21 patients.
Additionally, a retrospective study using a national cancer database that included roughly 12,300 Merkel cell carcinoma patients looked at survival outcomes in patients treated with surgery alone vs surgery plus radiation. For stage I and stage II patients, surgery plus radiation had improved survival compared with surgery alone, with hazard ratios of 0.75 and 0.77, respectively. As the discussant summarized these findings, it was recommended that the current National Comprehensive Cancer Network guidelines be revised for Merkel cell carcinoma management.
The recommendations proposed by the speaker included the use of radiation therapy after local excision in the presence of positive lymph nodes. It was also proposed that even with negative lymph nodes, overall survival may be increased by adding adjuvant radiation therapy for select patients. Furthermore, it remains unclear if radical lymph node dissection should be recommended in the presence of positive nodes—this may only have an impact on local control, rather than on overall survival. Further studies are necessary to clarify these recommendations.