Immunotherapy enhances or restores the immune system's ability to detect and destroy cancer cells. The development of immune checkpoint inhibitors, drugs that block inhibitory proteins (PD-1, PD-L1, CTLA-4) on T cells produces durable responses in some patients with previously untreatable disease and is highly effective for advanced stage skin cancers.2-7

• Pembrolizumab (Keytruda) is a PD-1 Inhibitor:2-4,6

  • • A monoclonal antibody that blocks the PD-1 receptor on T cells, preventing tumour cells from evading immune attack

    • Approved for advanced melanoma, advanced SCC, and advanced MCC

    • Clinical trials show overall survival benefits exceeding 30% in Stage IV melanoma when administered intravenously every 3–6 weeks

• Nivolumab (Opdivo) is also a PD-1 Inhibitor:5,7

  • • Approved for advanced melanoma

    • Often combined with Ipilimumab for Stage IV melanoma which the combination increases efficacy, and also significantly increases immune-related adverse events

• Cemiplimab (Libtayo) is another PD-1 Inhibitor:2-4

  • • Its the first immunotherapy approved specifically for advanced SCC

    • Approved for locally advanced or metastatic BCC that has progressed far or is intolerant to Hedgehog pathway inhibitors

• Ipilimumab (Yervoy) is a CTLA-4 Inhibitor:5,7

  • • Its the first immune checkpoint inhibitor approved for general use against cancer

    • Blocks CTLA-4 which is an inhibitory checkpoint, to enhance T-cell activation

    • Used for advanced melanoma, often in combination with nivolumab

    • It encompasses more serious immune-related side effects than PD-1 inhibitors.

Targeted therapy exploits specific molecular abnormalities within cancer cells.5,7

• BRAF Inhibitors (for BRAF-mutated Melanoma): Dabrafenib (Tafinlar), Vemurafenib (Zelboraf), and Encorafenib (Braftovi)5,7

  • • Selectively inhibits the mutant BRAF V600K/E kinase, blocking the MAP kinase/ERK proliferation pathway

    • Typically combined with a MEK inhibitor for maximal effect and to reduce resistance

• MEK Inhibitors (for BRAF-mutated Melanoma): Trametinib (Mekinist), Cobimetinib (Cotellic), and Binimetinib (Mektovi)5-7

  • • Inhibit MEK1/2 which are proteins downstream of BRAF in the same pathway

    • Combination of BRAF + MEK inhibitor therapy significantly delays the development of resistance compared to either drug alone

• Hedgehog Pathway Inhibitors (for locally advanced/metastatic BCC): Vismodegib (Erivedge) and Sonidegib (Odomzo)1

  • • Inhibit the Smoothened (SMO) receptor blocks Hedgehog pathway signalling that drives BCC growth

    • In BCC, the Hedgehog signalling pathway is inappropriately regulated in almost all cases due to mutations in the PTCH1 or SMO genes1

    • Vismodegib is the first-line choice for metastatic BCC, and common side effects include muscle spasms, hair loss, dysgeusia (taste changes), and weight loss

For patients with locally advanced BCC who progress on Hedgehog inhibitors, Cemiplimab (Libtayo) is now an approved second-line option.1

Radiation therapy uses high-energy X-rays or other particles to destroy cancer cells.1-7

• In skin cancer, it serves multiple roles:

  • • As a curative modality when surgery is not feasible

    • As an adjuvant treatment after surgery to reduce recurrence risk

    • As a palliative treatment to manage symptoms of advanced disease

• MCC:6

  • • Radiation therapy is the standard adjuvant treatment after surgical excision for MCC

    • It significantly reduces local and regional recurrence rates

• BCC and SCC:2-3

  • • Used when surgery is not possible due to tumour size/location or patient health

    • Used as adjuvant therapy after excision for high-risk features

• Melanoma:5,7

  • Radiation is used to shrink tumours that have metastasized

Systematic chemotherapy uses drugs that travel through the bloodstream to kill rapidly proliferating cancer cells. While largely replaced by immunotherapy for first-line treatment, it still remains a common option for metastatic or refractory cases.2

Commonly used to treat aggressive or metastatic SCC, MCC, and occasionally BCC when other treatments failed.2

• Cisplatin / Carboplatin:2

  • • Standard platinum-based agents used for advanced SCC and MCC

• Paclitaxel:2

  • • Used in combination with platinum-based drugs for aggressive MCC

• 5-Fluorouracil:2

  • • A intravenously administered (systematic) approach for advanced or metastatic disease