Highlights
- •Adjuvant therapy with nivolumab in stage IIIB/C–IV melanoma patients is superior to adjuvant therapy with ipilimumab.
- •Adjuvant therapy with the combination of dabrafenib and trametinib is superior to placebo in stage IIIA(>1 mm)/B/C melanoma patients.
- •These findings will put an end to the use of adjuvant ipilimumab.
- •Adjuvant interferon remains an option only for patients with ulcerated melanoma.
Abstract
The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab
in fully resected stage IIIB/C–IV and of the combination of dabrafenib (D) plus trametinib
(T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced
melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival
benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation
for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo
will complete the picture in the early 2018. Toxicity profiles are in line with the
experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and
problematic for ipilimumab. The 2017 outcomes are practice changing and put an end
to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN,
its use can be restricted to patients with ulcerated melanoma, based on the individual
patient data meta-analysis recently published. Because of the results of the Melanoma
Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND)
will decrease sharply, leading to a lack of optimal prognostic information. Prognosis
in sentinel node–positive stage IIIA/B patients is extremely heterogeneous with 5-year
survival rates varying from 90% to 40% and depends mostly on the number of positive
nodes identified by CLND. This information is crucial for clinical decision-making.
How to guarantee optimal staging information needs to be discussed urgently. Further
improvements of adjuvant therapies will have to address all these questions as well
as the exploration of neoadjuvant use of active drugs and combination approaches.
Important paradigm shifts in the management of high-risk melanoma patients are upon
us.
Keywords
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Article info
Publication history
Published online: September 29, 2017
Accepted:
September 18,
2017
Received:
September 18,
2017
Identification
Copyright
© 2017 Elsevier Ltd. All rights reserved.
