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Review
. 2019 May 22:11:1758835919851663.
doi: 10.1177/1758835919851663. eCollection 2019.

Management of metastatic cutaneous melanoma: updates in clinical practice

Gustavo Schvartsman  1 , Patricia Taranto  2 , Isabella C Glitza  3 , Sanjiv S Agarwala  4 , Michael B Atkins  5 , Antonio C Buzaid  6
Affiliations
Review

Management of metastatic cutaneous melanoma: updates in clinical practice

Gustavo Schvartsman et al. Ther Adv Med Oncol. .

Abstract

In recent years, several drugs have been approved for the treatment of patients with metastatic cutaneous melanoma, completely reshaping the landscape of this aggressive disease. Immune therapy with cytotoxic T-lymphocyte antigen 4 and programmed cell death-1 inhibitors yielded significant and durable responses, achieving long-term disease control in up to 40% of the patients. BRAF inhibitors (BRAFi), in combination with MEK inhibitors, also resulted in improved overall survival compared with single-agent BRAFi in patients with BRAFV600-mutated metastatic melanoma. The optimized sequencing and duration of treatment, however, is yet to be found. In this article, we thoroughly review current data and discuss how to best sequence the various treatment modalities available at present, based on four distinct clinical presentations commonly seen in clinic. In addition, we review treatment options beyond checkpoint inhibitors and targeted therapy, which may be required by patients failing such effective treatments.

Keywords: BRAF inhibitor; anti-PD-1; combination immunotherapy; immunotherapy; melanoma; metastatic brain tumors; targeted therapy; treatment sequencing.

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Conflict of interest statement

Conflict of interest statement: Antonio C. Buzaid has served on an advisory board for MSD, BMS, Roche, AstraZeneca, Novartis, Pfizer, Eisai, and Blau. Michael B. Atkins has served on an advisory board for BMS, MSD, Roche, Novartis, Pfizer, Array, Esai, and Exelixis. Gustavo Schvartsman has performed a consulting role for BMS, United Medical, and MSD. Isabella C. Glitza, Sanjiv S. Agarwala, and Patricia Taranto have no conflicts of interest to disclose.

Figures

Figure 1.
Figure 1.
Clinical scenario 1: algorithm for the management of patients with low-risk disease and no CNS involvement. BRAFi, BRAF inhibitor; CNS, central nervous system; HD IL-2, high-dose interleukin-2; Ipi + Nivo, ipilimumab + nivolumab; MEKi, MEK inhibitor; PD, progression of disease; RT, radiotherapy; SRS stereotactic radiosurgery.
Figure 2.
Figure 2.
Clinical scenario 2: algorithm for the management of patients with low-risk disease and brain metastases. BRAFi, BRAF inhibitor; Ipi + Nivo, ipilimumab + nivolumab; MEKi, MEK inhibitor; PD, progression of disease; SRS, stereotactic radiosurgery.
Figure 3.
Figure 3.
Clinical scenario 3: algorithm for the management of patients with high-risk disease and no CNS involvement. BRAFi, BRAF inhibitor; CNS, central nervous system; Ipi, ipilimumab; MEKi, MEK inhibitor; PR, partial response.
Figure 4.
Figure 4.
Clinical scenario 4: algorithm for the management of patients with high-risk disease and CNS involvement. BRAFi, BRAF inhibitor; CNS, central nervous system; Ipi, ipilimumab; MEKi, MEK inhibitor; PR, partial response; QT, chemotherapy; WBRT, whole-brain radiotherapy.
See this image and copyright information in PMC

References

    1. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 2011; 364: 2507–2516. - PMC - PubMed
    1. Larkin J, Minor D, D’Angelo S, et al. Overall survival in patients with advanced melanoma who received nivolumab versus investigator’s choice chemotherapy in checkmate 037: a randomized, controlled, open-label phase III trial. J Clin Oncol 2017: Jco2016718023. - PMC - PubMed
    1. Middleton MR, Grob J, Aaronson N, et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000; 18: 158–158. - PubMed
    1. Kottschade LA, Suman VJ, Amatruda T, 3rd, et al. A phase II trial of nab-paclitaxel (ABI-007) and carboplatin in patients with unresectable stage IV melanoma: a North Central Cancer Treatment Group Study, N057E(1). Cancer 2011; 117: 1704–1710. - PMC - PubMed
    1. McArthur GA, Chapman PB, Robert C, et al. Safety and efficacy of vemurafenib in BRAF V600E and BRAF V600K mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study. Lancet Oncol 2014; 15: 323–332. - PMC - PubMed