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Neoadjuvant Systemic Therapy for High-Risk Melanoma Patients

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Abstract

The landscape of treatment options and outcomes for patients with locally advanced and metastatic melanoma has changed dramatically in the past decade, with the introduction of molecularly targeted antitumor therapy and immunotherapy. Despite these recent advances for advanced stage melanoma, stage III melanoma patients have heterogeneous outcomes and have highly variable prognosis with respect to risk of loco-regional and distant recurrence and survival. Patients with clinical stage III disease, defined as those with palpable nodes with or without in-transit metastases, represent a high-risk population with poor outcomes even with the recent progress in adjuvant therapy. The full potential of targeted and immunotherapy, as well as other novel therapies, in the neoadjuvant setting is unknown and are only beginning to be investigated. Neoadjuvant therapy conveys advantages over administering the same treatment postoperatively as, in some cases, favorable response to treatment can make surgery less morbid and more effective. Additionally, response to therapy can be assessed and postoperative therapy adjusted accordingly depending on degree of response. Neoadjuvant therapy is associated with disadvantages as well; the exact stage of disease may be unknown when treatment begins, and adverse effects of treatment can negatively impact planned surgery or increase the risk of postoperative complications. The results of ongoing and future neoadjuvant clinical trials will undoubtedly shape the standard of care for patients with locally advanced melanoma at high risk of recurrence. Ultimately, enhanced selection of patients for systemic therapy prior to surgery could delay or prevent distant metastatic disease and improve survival for melanoma patients.

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Disclosures

Dr. Keung is supported by National Institutes of Health (NIH) grant T32 CA009599. Dr. Amaria receives research funding from Merck, Bristol-Myers Squibb, Iovance Biotherapetuics, Array Biopharma, and Genentech. Dr. Kirkwood receives research funding from Merck and Prometheus and is a consultant for Bristol Myers Squibb, Novartis, Array BioPharma, Merck, Roche, Amgen, and Immunocore. Dr. Sondak is a compensated consultant for Array, Bristol Myers Squibb, Genentech Roche, Merck, Novartis, Oncolys, Pfizer, and Polynoma. Dr. Wargo is an inventor on a US patent application (PCT/US17/53,717) submitted by The University of Texas MD Anderson Cancer Center that covers methods to enhance checkpoint blockade therapy by the microbiome; is a clinical and scientific advisor at Microbiome DX and a consultant at Biothera Pharma, Merck Sharp, and Dohme; has honoraria from speakers’ bureau of Dava Oncology, Bristol-Myers Squibb, and Illumina, Omniprex, Imedex; and is an advisory board member for GlaxoSmithKline, Novartis, and Roche/Genentech, Astra-Zeneca.

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Authors and Affiliations

  1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Emily Z. Keung, Merrick I. Ross & Jennifer A. Wargo

  2. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Rodabe N. Amaria

  3. Division of Hematology-Oncology, Department of Medicine, The University of Pittsburgh School of Medicine and UPMC Hillman Cancer Center, Pittsburgh, PA, USA

    John M. Kirkwood

  4. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Vernon K. Sondak

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  1. Emily Z. Keung
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  2. Rodabe N. Amaria
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  3. Vernon K. Sondak
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  4. Merrick I. Ross
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  5. John M. Kirkwood
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  6. Jennifer A. Wargo
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Corresponding author

Correspondence to Jennifer A. Wargo .

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Editors and Affiliations

  1. Division of Surgical Oncology, University of Texas Southwestern, Dallas, TX, USA

    Charles Balch

  2. Division of Surgery, UT MD Anderson Cancer Center, Houston, TX, USA

    Jeffrey Gershenwald

  3. Melanoma Institute of Australia, Wollstonecraft, Australia

    John Thompson

  4. Georgetown Medical Center, Washington, DC, USA

    Michael Atkins

  5. Melanoma and Skin Cancer Program, University of Pittsburgh, Pittsburgh, PA, USA

    John Kirkwood

  6. University of Sydney, Sydney, NSW, Australia

    Richard Kefford

  7. Department of Dermatology, Harvard Medical Center, Boston, MA, USA

    Arthur Sober

  8. Department of Dermatology, Memorial Sloan Kettering, New York, NY, USA

    Allan Halpern

  9. Department of Dermatology, University Hospital, Tübingen, Tübingen, Germany

    Claus Garbe

  10. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown NSW, Australia

    Richard Scolyer

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Keung, E.Z., Amaria, R.N., Sondak, V.K., Ross, M.I., Kirkwood, J.M., Wargo, J.A. (2019). Neoadjuvant Systemic Therapy for High-Risk Melanoma Patients. In: Balch, C., et al. Cutaneous Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-46029-1_70-1

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