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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Merkel cell carcinoma is a rare, fast-growing skin cancer, usually caused by a common virus (Merkel cell polyomavirus) or by sun damage. Once it had spread there was no treatment that worked; PD-1/PD-L1 immunotherapy now gives lasting responses in about half of patients.
Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer of older, fair-skinned and immunosuppressed people. About 80% of cases in the Northern Hemisphere are driven by clonally integrated Merkel cell polyomavirus (MCPyV, discovered 2008); the remainder are UV-induced with a very high tumour mutational burden. Both forms are immunogenic, which explains why MCC responded to checkpoint blockade when chemotherapy gave only brief responses.
Localised disease is treated with wide excision, sentinel node biopsy and adjuvant radiotherapy; the STAMP and ADMEC-O trials tested adjuvant PD-1 blockade, with ADMEC-O (nivolumab) showing a disease-free survival benefit in 2023. Metastatic disease is treated first line with avelumab (JAVELIN Merkel 200, first approval 2017), pembrolizumab (KEYNOTE-017, 2018) or retifanlimab (POD1UM-201, 2023); durable responses occur in about half, and chemotherapy is reserved for immunotherapy failure. Circulating MCPyV oncoprotein antibodies (AMERK) allow surveillance in seropositive patients.
| Setting | Approach | Guideline |
|---|---|---|
| Localised (stage I-II) | Wide local excision with sentinel node biopsy; adjuvant radiotherapy to the primary site (and nodal basin if node-positive); adjuvant nivolumab supported by ADMEC-O in selected patients. | NCCN Category 2A |
| Regional nodal disease (stage III) | Lymphadenectomy and/or nodal radiotherapy; neoadjuvant nivolumab (CheckMate 358) produced pathological complete responses in about half. | not mapped |
| Metastatic, first line | Avelumab, pembrolizumab or retifanlimab; ~50% response with most responses durable. | NCCN Category 2A (preferred) |
| Immunotherapy-refractory | Platinum-etoposide chemotherapy (brief responses), radiotherapy, clinical trials (ipilimumab-nivolumab, T-VEC, adoptive T cells). | not mapped |
| Choosing among the three PD-1 pathway antibodies | Avelumab, pembrolizumab and retifanlimab are all approved and none has been compared with another. First-line response was 39.7 per cent with avelumab in 116 patients, 56 per cent with pembrolizumab in 50 and 54.5 per cent with retifanlimab in 101. The retifanlimab study is the most fully reported: 17.8 per cent complete responses, median duration of response not reached in complete responders and 25.3 months in partial responders, median progression-free survival 16.0 months, and 63 per cent of patients alive at three years, in a disease where chemotherapy responses were measured in months. Grade 3 immune-related adverse events occurred in 10.9 per cent. Which antibody is used matters far less than that roughly half of patients respond and most responders keep responding. | NCCN Category 2A |
| After complete resection: what the adjuvant evidence does and does not show | ADMEC-O randomised 179 patients with completely resected Merkel cell carcinoma 2 to 1 to a year of nivolumab or to observation. Disease-free survival was 85 per cent at 12 months and 84 per cent at 24 with nivolumab against 77 and 73 per cent with observation, a hazard ratio of 0.58 whose 95 per cent confidence interval, 0.30 to 1.12, crosses one; the authors state it as an absolute risk reduction of 9 and 10 percentage points. Grade 3 or 4 adverse events occurred in 42 per cent against 11 per cent. Overall survival had ten events against six in a group half the size and is not mature. This is a phase 2 signal in a rare disease, not a proven standard, and the randomised phase 3 that would settle it, STAMP, has not reported. | not mapped |
| What is available in England | NICE technology appraisal TA691 recommendation 1.1 recommends avelumab for metastatic Merkel cell carcinoma in adults who have not had chemotherapy for metastatic disease, under a commercial arrangement, on evidence collected in the Cancer Drugs Fund under TA517. TA517 recommendation 1.1 continues to cover its use after one or more lines of chemotherapy. Pembrolizumab and retifanlimab have no NICE appraisal for this disease. | not mapped |