Systemic Adjuvant Therapy for Adult Patients at High Risk for Recurrent Cutaneous or Mucosal Melanoma: An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline

Abstract

Background Previous versions of the guideline from the Program in Evidence-Based Care (pebc) at Ontario Health (Cancer Care Ontario) recommended that the use of high-dose interferon alfa 2b therapy be discussed and offered to patients with resected cutaneous melanoma with a high risk of recurrence. Subsequently, several clinical trials in patients with resected or metastatic melanoma found that immune checkpoint inhibitors and targeted therapies have a benefit greater than that with interferon. It was therefore considered timely for an update to the guideline about adjuvant systemic therapy in melanoma.Methods The present guideline was developed by the pebc and the Melanoma Disease Site Group (dsg). Based on a systematic review from a literature search conducted using medline, embase, and the Evidence Based Medicine Reviews databases for the period 1996 to 28 May 2019, the Working Group drafted recommendations. The systematic review and recommendations were then circulated to the Melanoma dsg and the pebc Report Approval Panel for internal review; the revised document underwent external review.Recommendations For patients with completely resected cutaneous or mucosal melanoma with a high risk of recurrence, the recommended adjuvant therapies are nivolumab, pembrolizumab, or dabrafenib–trametinib for patients with BRAF V600E or V600K mutations; nivolumab or pembrolizumab are recommend for patients with BRAF wildtype disease. Use of ipilimumab is not recommended. Molecular testing should be conducted to help guide treatment decisions. Interferon alfa, chemotherapy regimens, vaccines, levamisole, bevacizumab, bacillus Calmette–Guérin, and isolated limb perfusion are not recommended for adjuvant treatment of cutaneous melanoma except as part of a clinical trial.

Evaluation of treatment, prognostic factors, and survival in 198 vulvar melanoma patients: Implications for clinical practice

“…Immune checkpoint inhibition (ICI) with anti-CTLA-4 and anti-PD-1 have improved survival for unresectable or metastatic CM and are now standardof care forpatients with high-risk (i.e., AJCCstage IIIand resected stage IV) and advanced (i.e., irresectable stage IIIC and IV) CM. [27][28][29][30]. The efficacy of anti-CTLA-4 and anti-PD-1 antibodies has not been specifically evaluated in larger cohorts of patients with MM and prospective trials in VM have not been performed.…”

RAGE Signaling in Melanoma Tumors

“…Although most melanoma tumors develop in the skin (cutaneous melanoma), they can also arise in mucosal membranes, [10][11][12][13][14][15][16][17], in the eye (uveal melanoma) [18], and primary melanoma tumors have also been described in leptomeninges (Table 1) [19]. Among these different types of melanoma, cutaneous melanoma is by far the most prevalent.…”

Locoregional Management of in-Transit Metastasis in Melanoma: An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline

“…Adjuvant systemic therapy may be considered for itm being surgically resected. For recommendations about adjuvant systemic therapy, consult the pebc guideline on adjuvant systemic therapy 19 .…”

“…This recommendation was based on the expert opinion of the Working Group and is currently the standard of practice within cancer centres in Canada. If adjuvant therapy is being considered as an option for affected patients, the pebc guideline on systemic adjuvant therapy outlines the appropriate systemic therapies based on the clinical evidence and should be consulted 19,21 .…”

“…Although systemic therapy is not reviewed in this guideline, it may be considered in patients with maximal itm. Immunotherapy and targeted therapy have been found to be of benefit in the metastatic setting and for adjuvant use in completely resected melanoma 19 .…”