The Adjuvant Treatment of Cutaneous Melanoma Just Became Interesting

Andrew D. Kin, Amy M Weise

Abstract


Until recently, melanoma was a very challenging cancer to treat.  The only adjuvant therapy available for years was interferon, which was associated with significant toxicity.  Advances in metastatic melanoma, namely the development of immunotherapies and targeted therapies, have rapidly changed the standard of care for patients with advanced or high risk local disease.

Ipilimumab was the first immunotherapy approved after demonstrating a relapse free survival (RFS) of 26.1 months compared to 17.1 months with placebo, and subsequently demonstrated a 10% difference in overall survival at 5 years, although with significant toxicity.  Nivolumab and now pembrolizumab have also demonstrated prolonged RFS by about 10% at one year, with a hazard ratio for each around 0.55, each with much lower toxicity than ipilimumab.  Targeted therapy combinations with the BRAF and MEK inhibitors dabrafenib and trametinib have shown a 20% improvement in median RFS at 18 months with hazard ratio of 0.47.  The introduction of novel classes of therapy in the adjuvant setting has shown dramatic improvement in toxicity, tolerability, and survival.  This has changed the standard of therapy for adjuvant melanoma and raised additional questions on overall patient management.


Keywords


melanoma; adjuvant; nivolumab; dabrafenib; trametinib; pembrolizumab; ipilimumab

Full Text:

PDF

References


NIH Cancer Stat Facts: Melanoma of the Skin. https://seer.cancer.gov/statfacts/html/melan.html. 2015.

Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199-206.

Svedman FC, Pillas D, Taylor A, Kaur M, Linder R, Hansson J. Stage-specific survival and recurrence in patients with cutaneous malignant melanoma in Europe - a systematic review of the literature. Clin Epidemiol. 2016;8:109-22.

Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol. 1996;14(1):7-17.

Eggermont AM, Suciu S, Santinami M, Testori A, Kruit WH, Marsden J, et al. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008;372(9633):117-26.

Callahan MK, Wolchok JD, Allison JP. Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy. Semin Oncol. 2010;37(5):473-84.

Eggermont AMM, Chiarion-Sileni V, Grob J-J, Dummer R, Wolchok JD, Schmidt H, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. The Lancet Oncology. 2015;16(5):522-30.

Jin HT, Ahmed R, Okazaki T. Role of PD-1 in regulating T-cell immunity. Curr Top Microbiol Immunol. 2011;350:17-37.

Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017;377(19):1824-35.

Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson V, Dalle S, et al. Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. N Engl J Med. 2018;378(19):1789-801.

Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371(20):1877-88.

Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372(1):30-9.

Long GV, Hauschild A, Santinami M, Atkinson V, Mandala M, Chiarion-Sileni V, et al. Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med. 2017;377(19):1813-23.

Maio M, Lewis K, Demidov L, Mandalà M, Bondarenko I, Ascierto PA, et al. Adjuvant vemurafenib in resected, BRAF V600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. The Lancet Oncology. 2018;19(4):510-20.

Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma. N Engl J Med. 2017;376(23):2211-22.

Leiter U, Stadler R, Mauch C, Hohenberger W, Brockmeyer N, Berking C, et al. Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. The Lancet Oncology. 2016;17(6):757-67.




DOI: http://dx.doi.org/10.18103/imr.v4i7.736

Refbacks

  • There are currently no refbacks.
Copyright 2016. All rights reserved.