Abstract
Simple SummaryAdjuvant treatment with the immune checkpoint inhibitors (ICI) pembrolizumab or nivolumab, or the targeted therapies dabrafenib and trametinib is recommended for patients with completely resected stage III melanoma and significantly decreases recurrence risk. Currently, limited data are available on physicians’ prescription preferences regarding ICI and targeted therapies and patient outcome in clinical practice. This study investigates the real-world situation of 109 patients from the Cancer Center of the University Hospital Bern, Switzerland, with an indication for adjuvant treatment since 2018. We describe treatment patterns, recurrence, and toxicity rates under immune checkpoint inhibitors, and targeted therapies.Approved adjuvant treatment options for stage III melanoma are the immune checkpoint inhibitors (ICI) pembrolizumab and nivolumab, and in presence of a BRAF V600E/K mutation additionally dabrafenib in combination with trametinib (BRAFi/MEKi). This study aims to describe prescription patterns and recurrence and toxicity rates of adjuvant-treated melanoma patients from the Cancer Center of the University Hospital Bern, Switzerland. One hundred and nine patients with an indication for adjuvant treatment were identified. Five (4.6%) had contraindications and, as such, were not proposed any adjuvant treatment, while 10 patients (9.2%) declined treatment. BRAF status was known for 91 (83.5%) patients. Of 40 (36.7%) patients with BRAF V600E/K melanoma, pembrolizumab was prescribed to 18 (45.0%), nivolumab to 16 (40.0%), and dabrafenib/trametinib to three (7.5%) patients. Grade 3–4 toxicity was reported in 18.9% and 16.7% of all the patients treated with pembrolizumab and nivolumab, respectively. No toxicities were observed for dabrafenib/trametinib. Thirty-eight percent of the patients treated with pembrolizumab and 40.0% of those treated with nivolumab relapsed. No relapses were reported for dabrafenib/trametinib. Prescription patterns indicate a clear preference for adjuvant ICI treatment.
Highlights
Patients with stage III melanoma are at high risk of relapse, with a melanoma specific5-year survival ranging from 93% (IIIA) to 32% (IIID) [1]
The aim of our analysis is to describe prescription patterns, recurrence, and toxicity rates of adjuvant treatments for resected stage III/IV melanoma in daily practice, including comparing physicians’ preferences for immune checkpoint inhibitors (ICI) versus BRAF inhibitor (BRAFi)/MEK inhibitor (MEKi) for BRAF V600E/K mutant melanoma
The BRAF status was known in 83.5% of patients (N = 91), a BRAF V600E/K mutation was detected in 36.7% of patients (N = 40), and an atypical BRAF mutation was found in 3.7% (N = 4) of the samples
Summary
Patients with stage III melanoma are at high risk of relapse, with a melanoma specific5-year survival ranging from 93% (IIIA) to 32% (IIID) [1]. Randomized controlled phase 3 trials have shown a significant improvement in recurrence-free survival (RFS) with adjuvant ICI or BRAFi/MEKi for stage III or IV melanoma with no evidence of disease. These trials classified disease according to the American Joint Committee on Cancer (AJCC) 7th edition, which was replaced in 2017 by the 8th edition. The COMBI-AD trial has shown an improved RFS (HR 0.47; 95% CI, 0.42 to 0.61) for BRAF V600E/K-positive IIIA (with >1 mm lymph node metastasis), IIIB, and IIIC patients receiving dabrafenib and trametinib versus a placebo doublet [5]
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