Prescription Patterns, Recurrence, and Toxicity Rates of Adjuvant Treatment for Stage III/IV Melanoma—A Real World Single-Center Analysis

Abstract

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.

Application of Electronic Health Record Text Mining: Real-World Tolerability, Safety, and Efficacy of Adjuvant Melanoma Treatments

“…However, both for dabrafenib plus trametinib and nivolumab, the relative number of patients who ended treatment due to toxicity was higher than in the trials. This was also observed in the studies of de Meza et al and Hoffmann et al, which showed higher treatment-limiting AEs on ICI in clinical practice [ 21 , 22 ]. As far as we know, no other real-world data have been published with treatment-limiting toxicity rates for dabrafenib plus trametinib.…”

“…De Meza et al showed comparable 1-year survival rates of 87.0% for the stage IIIA, and 76.5% for stage IIIB, and 60.3% for stage IIIC in a population treated with ICI in Dutch clinical practice [ 21 ]. Hoffmann et al showed a RFS at 1-year of 77.1% after nivolumab and 63.5% after pembrolizumab in a Swiss population [ 22 ]. Furthermore, even though Koelblinger et al showed a 1-year RFS rate of 64.8% in an Austrian population, they showed comparable distant metastasis free-survival compared to the Checkmate-238 trial (77.4% vs. 80%), and concluded treatment cost-effectiveness for the Austrian population [ 34 ].…”

“…All real-world studies showed comparable effectiveness to the RCTs, which is in line with our premature results. Hoffmann et al is to our knowledge the only published study reviewing dabrafenib plus trametinib in clinical practice; however, they only included three patients who finished their treatment [ 22 ].…”

Immunotherapy for Melanoma: The Significance of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma

“…Since melanoma is one of the most fatal skin tumors, several adjuvant therapies for advanced melanoma have been developed over the decades [ 5 ]. Of them, both nivolumab and pembrolizumab are approved for melanoma at high risk of recurrence, especially BRAF wild-type melanoma [ 9 , 16 , 17 ]. Indeed, nivolumab achieved a 4-year recurrence-free survival (RFS) rate of 51.7% and a 4-year OS of 77.9% in stage III-IV melanoma patients in the adjuvant setting [ 9 ].…”

“…In addition, the efficacy of anti-PD1 Abs as adjuvant therapy for up to approximately 1 year for stage III melanoma was significantly lower in acral melanoma than in cutaneous melanoma in a Japanese cohort (31 acral melanoma vs. 31 cutaneous melanoma patients, p = 0.026) [ 9 ]. The safety profiles of nivolumab and pembrolizumab in the adjuvant setting are comparable to those for unresectable melanoma [ 9 , 16 , 17 ]. Collectively, anti-PD1 Abs in the adjuvant setting are less effective for acral melanoma than for cutaneous melanoma.…”