Non-Melanoma Skin Cancers: Systemic Therapy

Non-Melanoma Skin Cancers: overview

This algorithm addresses systemic therapy for advanced non-melanoma skin cancers, with the first branch point being histology. For Merkel cell carcinoma, checkpoint inhibitors are first-line: avelumab (JAVELIN Merkel) or pembrolizumab or retifanlimab, linked to KEYNOTE-017. In KEYNOTE-017, first-line pembrolizumab produced a 56% response rate with durable responses in advanced Merkel cell carcinoma.

For advanced cutaneous squamous cell carcinoma, immunotherapy is again the first-line approach, with cemiplimab (EMPOWER-CSCC) or pembrolizumab (KEYNOTE-629). KEYNOTE-629 was the single-arm dataset supporting pembrolizumab as an alternative to cemiplimab in recurrent or metastatic disease. For advanced basal cell carcinoma, hedgehog pathway inhibitors (vismodegib or sonidegib, from ERIVANCE / BOLT) are first-line, and cemiplimab is the checkpoint inhibitor option after hedgehog inhibitor therapy. Across all three histologies, the chart positions PD-1 or PD-L1 blockade as the backbone of systemic therapy, with the exception of hedgehog inhibition as initial therapy in basal cell carcinoma.

Trials behind this algorithm

• JAVELIN Merkel 200 Kaufman HL et al, Lancet Oncol, 2016; PMID: 27592805
• KEYNOTE-017 Nghiem PT et al, NEJM, 2016; PMID: 27093365
• EMPOWER-CSCC-1 Migden MR et al, NEJM, 2018; PMID: 29863979
• KEYNOTE-629 Grob JJ et al, JCO, 2020; PMID: 32673170
• ERIVANCE BCC Sekulic A et al, NEJM, 2012; PMID: 22670903