Lay Summary: Merkel Cell Carcinoma is a rare skin cancer; treatment options are discussed.
Merkel cell carcinoma (MCC) is an aggressive yet uncommon neoplasm that often arises on the head and neck. Because of the rarity of the tumor, however, diagnosis and treatment have previously been based more on anecdotal data than on scientific data. Because of the high degree of local recurrence and early lymph node and distant metastases in patients with NEC, patients should be treated aggressively at the time of initial diagnoses. Although no widely adopted classification system exists, treatment guidelines have been based on three clinical stages of disease: local disease without lymph node or systemic involvement (stage I), regional lymph node development without systemic disease (stage II), and systemic metastases (stage III). Most treatment guidelines include wide excision of the primary tumor, alone or in combination with adjuvant radiation therapy, therapeutic regional lymph node dissection, or elective regional lymph node dissection. This patient has loco-regional disease which is usually treated with wide resection and adjuvant radiation. Some recommend adjuvant chemo and there is little information on which to base firm recommendations. Merkel cell carcinoma is associated with the Merkel cell polyomavirus in ~80% of patients. The other 20% of patients harbor a heavy ultraviolet-induced mutation load. Until recently, chemotherapy was the only treatment option for unresectable disease. In 2017, avelumab became the first drug ever approved by the U.S. Food and Drug Administration for Merkel cell carcinoma. Pembrolizumab and nivolumab have shown similar efficacy in metastatic disease, and their approval in this setting is pending. Updates of these studies were presented at the ASCO meeting, as were new data for neoadjuvant nivolumab.
Clinical stage III disease usually presents in the bone, abdomen, skin, mediastinum, lung, liver, or basin. The usual time span from diagnosis of stage III disease to death is 8 months. Chemotherapy is the treatment most often employed within this setting. However, as in the case of all other treatment modalities used against this tumor, the rarity of the condition precludes the availability of statistically significant comparisons. No firmly established chemotherapy for MCC exists. Because of the neuroendocrine features of this tumor, it has been treated with etoposide and cisplatin as well as with cisplatin and 5-fluorouracil. More recently, there are anecdotal reports of responses to paclitaxel. Unfortunately, the rarity of this tumor has prevented cooperative efforts to establish a firm basis for a recommended therapy.
NCCN mentions adriamycin, cytoxan AND vincristine or cisplatin or carboplatin/etoposide for metastatic disease but for first line only. Recently David et al rep0rted a case of response to Votrient and others who treat this disease anecdotally also reported success. However, there remain no prospective trials of this treatment.
Merkel cell carcinoma is a rare, aggressive, and often fatal skin cancer that is associated with the Merkel cell polyomavirus in ~80% of patients. The other 20% of patients harbor a heavy ultraviolet-induced mutation load. Until recently, chemotherapy was the only treatment option for unresectable disease. In 2017, avelumab became the first drug ever approved by the U.S. Food and Drug Administration for Merkel cell carcinoma. Pembrolizumab and nivolumab have shown similar efficacy in metastatic disease, and their approval in this setting is pending. Updates of these studies were presented at the ASCO meeting, as were new data for neoadjuvant nivolumab.
Radiographic regression by computed tomography was noted for 40% of 25 evaluable patients, in whom target lesions were reduced by more than 30%, she reported. Dr. Topalian added that radiographic response underestimated the impact of nivolumab in this short treatment interval; a better reflection was pathologic tumor response.
In 17 tumors evaluated by central pathologic review, the researchers documented a 47% rate of pathologic complete response by traditional criteria and an 18% major pathologic response rate, defined as up to 10% viable tumor cells remaining. These preliminary data yielded a total major pathologic response rate of 65% by central review. Some responses were striking. There were a significant number of patients in the trial with complete responses who had come off therapy about 1 to 2 years earlier and remained free of disease.
http://www.nccn.org/professionals/physician_gls/PDF/mcc.pdf, p.12, 2019
1.Topalian SL, Bhatia S, Kudchadkar RR, et al: Nivolumab as neoadjuvant therapy in patients with resectable Merkel cell carcinoma in CheckMate 358. 2018 ASCO Annual Meeting. Abstract 9505. Presented June 4, 2018.
2. Nghiem P, Bhatia S, Brohl AS, et al: Two-year efficacy and safety update from JAVELIN Merkel 200 part A: A registrational study of avelumab in metastatic Merkel cell carcinoma progressed on chemotherapy. 2018 ASCO Annual Meeting. Abstract 9507. Presented June 4, 2018.
3. Nghiem P, Bhatia S, Lipson EJ, et al: Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy. 2018 ASCO Annual Meeting. Abstract 9506. Presented June 4, 2018.
4. Nghiem PT, Bhatia S, Lipson EJ, et al: PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med 374:2542-2552, 2016.