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Neoadjuvant systemic therapy for Merkel cell carcinoma: A Tertiary Referral Center Experience

      Background and Aims: Merkel cell carcinoma (MCC) is an aggressive malignancy for which systemic therapy is standard of care in advanced disease. We assessed our institution’s experience with neoadjuvant systemic therapy (NST) in patients (pts) with surgically resectable MCC. Methods: A retrospective review of MCC patients who underwent surgery within the Dept. of Surgical Oncology at our institution from 2017 to 2021 was performed. Pts who received NST were identified and clinical characteristics, treatments received, pathological response and recurrence were examined. Pts with clinically positive nodal disease and in-transit lesions were considered for NST. Results: Of 93 pts identified, 18 received NST. Fourteen of these 18 pts (78%) presented with palpable nodal disease, 3 (17%) were found to have nodal disease on imaging and 1 had locally advanced MCC with in-transit disease. Sixteen (89%) pts underwent lymphadenectomy, 1 underwent wide local excision (WLE) and sentinel lymph node biopsy followed by definitive nodal radiation (RT), and 1 underwent WLE and primary site RT. Prior to surgery, 16 pts (89%) received 1 line of NST (10 avelumab, 2 pembrolizumab, 4 platinum-based chemotherapy and etoposide). Two (11%) pts received immunotherapy followed by chemotherapy. With median follow-up of 26.1 months (range 1.2-66.2) after surgery, median RFS and OS were not reached. Complete pathological response (pCR) was seen in 8 (44%) pts: 3 received avelumab, 1 avelumab with concurrent RT, 2 carboplatin/etoposide, and 2 had disease progression on immunotherapy but responded to chemotherapy. Partial pathological response (pPR) was observed in 5 (28%) pts and no response (NR) in 5 (28%) pts. Following surgery, 8 (44%) pts developed recurrent disease; 3 (17%) expired. Of those who had thus far recurred, 1 had pCR, 3had pPR and 4 NR at surgery. Radiographic response to neoadjuvant therapy was noted in 9 (50%) pts, of whom 6 achieved pCR, 2 pPR and 1 no pathological response at surgery. Conclusions: MCC pts in this series exhibited responses to NST, although a subset of patients appear to respond poorly to immunotherapy compared to chemotherapy. Studies are needed to determine appropriate NST and if NST confers a survival benefit.