Cutaneous Complications of Targeted Melanoma Therapy

Abstract

The landscape of advanced and metastatic melanoma therapy has shifted dramatically in recent years. Since 2011, eight drugs (ipilimumab, vemurafenib, dabrafenib, trametinib, cometinib, pembrolizumab, nivolumab, and talimogene laherparepvec) have received FDA approval for the treatment of advanced or metastatic melanoma, including combination regimens of both small molecule kinase and immune checkpoint inhibitors. These therapies have revolutionized the management of unresectable regional nodal and distant melanoma, providing hope of extended survival to patients. As the use of novel agents has increased, so have the cutaneous toxicities associated with these medications. While most skin reactions are low-grade and can be managed conservatively with topical therapies, malignant lesions and more serious or life-threatening drug reactions can arise during therapy, requiring prompt dermatologic recognition and treatment in order to improve patient outcome. Given the survival benefit attributed to these new agents, treating skin toxicity and maintaining patient quality of life is of paramount importance. Oncologists should be aware of the common cutaneous toxicities associated with these medications and should be encouraged to involve dermatologists in the collaborative care of advanced melanoma patients. Close communication between oncologists and dermatologists can help to avoid unnecessary dose reduction or treatment discontinuation and identify situations when treatment cessation is truly warranted.

Eruptive keratoacanthomas arising in the setting of lichenoid toxicity after programmed cell death 1 inhibition with nivolumab

“…Due to the large number of lesions, a nonsurgical approach, such as topical therapy, may be preferable for eruptive keratoacanthomatous proliferations. Treatment with other agents shown to have success with reactive KAs, such as oral retinoids, 6 may also prove beneficial.…”

Panniculitis in a patient with pathologic complete response to talimogene laherparepvec treatment for recurrent, in‐transit melanoma

“…However, much like systemic ICI therapy, T‐VEC can cause immune‐related adverse events (irAEs). Systemic ICIs commonly lead to dermatologic toxicity, and a wide spectrum of reactions have been reported, broadly characterized as inflammatory, immunobullous, alteration of keratinocytes, and alteration of melanocytes . The full spectrum of potential adverse events with T‐VEC is unknown.…”

Do current approaches to assessing therapy related adverse events align with the needs of long-term cancer patients and survivors?

“…The timespan of cancer therapy administration, care, and outcome is shifting from primarily acute treatment settings to a broad range of chronic adjuvant therapy and survivorship settings [12][13][14]. Treatment-related AEs may span in severity from potentially lethal cardiotoxicities to less dire but still debilitating systemic events, including fatigue, gastrointestinal issues, skin inflammation, and neuropathy [15][16][17][18][19][20][21]. The cumulative effect of these outcomes can vary considerably from patient to patient.…”