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Chapter 109: Melanoma

Nicholas Brownstone; Danny Zakria; Darrell S. Rigel

MELANOMA

Therapeutic approach

Melanoma is the most serious form of skin cancer causing most of the skin cancer-related deaths. Subtypes include superficial spreading, nodular, lentigo maligna and acral lentiginous.1 Early detection of malignant melanoma remains the key factor in lowering mortality which highlights the importance of the ABCDE screening acronym.2 The prognosis in melanoma is directly proportionate to the depth of the neoplasm, which in turn increases with time.3 Sentinel lymph biopsy is indicated for patients with a significant risk of melanoma metastasis and is used to assess prognosis. Therapy is dictated by stage at diagnosis and can include surgery, small molecule inhibitors, immunotherapy, chemotherapy, and topical therapy. Combination therapy with newer agents have been shown to delay development of resistance and improve treatment outcomes.4 See Table 109-1.

Table 109-1Melanoma Treatment Table
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Table 109-1 Melanoma Treatment Table
MEDICATION NAME INDICATION MECHANISM OF ACTION DOSING ADVERSE EFFECTS SUGGESTED MONITORINGa LEVEL OF EVIDENCE (REFERENCE)
Topical Therapy
Imiquimod 2nd line therapy for MIS, LM Induction of proinflammatory cytokines leading to a TH1 response5 5% cream applied topically for 5 d/wk for 12 wk (varies)5 Burning, tenderness, vesicular eruption, ulceration5 None IB6
Systemic Therapy
Vemurafenib Metastatic CM with BRAF V600 activation mutation BRAF inhibitor 960 mg PO BID7 Skin, hair8 EKG, CMP, TBSE, OE7 IB9
Dabrafenib Unresectable or metastatic melanoma BRAF inhibitor 150 mg PO BID10 Skin, hair8 CBC, glucose, OE, skin10 IB11
Trametinib Unresectable or metastatic melanoma MEK inhibitor 2 mg PO QD or combination with dabrafenib 150 mg PO BID12 Skin, GI, ocular, cardiac4 CBC, OE, glucose, BP, skin12 IB13
Cobimetinib Unresectable or metastatic melanoma combined with Vemurafenib MEK inhibitor 60 mg PO QD for the first 21 d of each 28-d cycle until disease progression or unacceptable toxicity14 Skin, GI, cardiac, Joints4 LFTs, EKG, skin14 IB15
Ipilimumab Unresectable or metastatic melanoma, + lymph nodes16 Immune checkpoint inhibitor (anti-CTLA4) 3 mg/kg IV q3wk for 4 total doses16 Skin, GI, endocrine, pulmonary, kidney, blood, ocular4,8 CMP, ACTH, TFTs16 IB17
Pembrolizumab Unresectable or metastatic melanoma, adjuvant treatment of stage IIB, IIC, or III in adult/pediatric pts s/p resection18 Immune checkpoint inhibitor (PD-1) 200 mg every 3 wk or 400 mg every 6 wk, 2 mg/kg (up to 200 mg) every 3 wk for pediatrics18 Skin, GI, endocrine, pulmonary, kidney, blood, ocular4,8 LFTs, Cr, TFTs18 IB19
Nivolumab Unresectable/metastatic melanoma as a single agent or in combo with ipilimumab, adjuvant treatment with + lymph nodes20 Immune checkpoint inhibitor (PD-1) 240 mg q2wk or 480 mg q4wk IV, 1 mg/kg followed by ipilimumab20 Skin, GI, endocrine, pulmonary, kidney, heme, ocular4,8 LFTs, TFTs, CMP, neuro exam, CXR...

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