Adjuvant Therapy for Melanoma

Agha, Aya; Tarhini, Ahmad A.

doi:10.1007/s11912-017-0594-5

Cited by 26 publications

(17 citation statements)

References 46 publications

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“…In the past, adjuvant therapies for melanoma were mainly based on interferon or ipilimumab, and were often characterized by low efficacy and severe adverse events . However, these new results using targeted and immunotherapies revive adjuvant strategies and foreshadow a new era of proactive cancer therapy.…”

mentioning

confidence: 99%

A new era of proactive melanoma therapy: hit hard, hit early

Haas

Wiesner

Obenauf

2018

British Journal of Dermatology

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confidence: 99%

A new era of proactive melanoma therapy: hit hard, hit early

Haas

Wiesner

Obenauf

2018

British Journal of Dermatology

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“…Monoactivity of interferon-α is commonly weak among quite different tumor types (Eggermont et al, 2008 ). Therefore, the drug did not find its way in routine use or novel drugs are meanwhile more active, for example in melanoma (Agha and Tarhini, 2017 ).…”

Section: Master Modulators the Backbone Of Anakoinosis Inducing Thermentioning

confidence: 99%

Clinical Efficacy of a Novel Therapeutic Principle, Anakoinosis

et al. 2018

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Classic tumor therapy, consisting of cytotoxic agents and/or targeted therapy, has not overcome therapeutic limitations like poor risk genetic parameters, genetic heterogeneity at different metastatic sites or the problem of undruggable targets. Here we summarize data and trials principally following a completely different treatment concept tackling systems biologic processes: the principle of communicative reprogramming of tumor tissues, i.e., anakoinosis (ancient greek for communication), aims at establishing novel communicative behavior of tumor tissue, the hosting organ and organism via re-modeling gene expression, thus recovering differentiation, and apoptosis competence leading to cancer control – in contrast to an immediate, “poisoning” with maximal tolerable doses of targeted or cytotoxic therapies. Therefore, we introduce the term “Master modulators” for drugs or drug combinations promoting evolutionary processes or regulating homeostatic pathways. These “master modulators” comprise a broad diversity of drugs, characterized by the capacity for reprogramming tumor tissues, i.e., transcriptional modulators, metronomic low-dose chemotherapy, epigenetically modifying agents, protein binding pro-anakoinotic drugs, such as COX-2 inhibitors, IMiDs etc., or for example differentiation inducing therapies. Data on 97 anakoinosis inducing schedules indicate a favorable toxicity profile: The combined administration of master modulators, frequently (with poor or no monoactivity) may even induce continuous complete remission in refractory metastatic neoplasia, irrespectively of the tumor type. That means recessive components of the tumor, successively developing during tumor ontogenesis, are accessible by regulatory active drug combinations in a therapeutically meaningful way. Drug selection is now dependent on situative systems characteristics, to less extent histology dependent. To sum up, anakoinosis represents a new substantive therapy principle besides novel targeted therapies.

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“…Adjuvant immunotherapy remains controversial in early-stage melanoma due to concerns for rare and in some cases lethal toxicities. Furthermore, the long-term impacts of immunotherapy on quality-of-life have not been studied (13)(14)(15)(16)(17). Although many melanoma clinicians recommend immunotherapy for stage IIIC-D disease, the role of immunotherapy in stage II-IIIB disease remains debatable, despite recent findings that adjuvant pembrolizumab, adjuvant ipilimumab, and adjuvant nivolumab each independently show a recurrence-free survival (RFS) benefit in stage III disease (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II–III Melanoma

Gartrell

Marks

Rizk

et al. 2019

Clinical Cancer Research

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Purpose: Biomarkers are needed to stratify patients with stage II-III melanoma for clinical trials of adjuvant therapy because, while immunotherapy is protective, it also confers the risk of severe toxicity. We previously defined and validated a 53-immune gene melanoma immune profile (MIP) predictive both of distant metastatic recurrence and of disease-specific survival (DSS). Here, we test MIP on a third independent population.Experimental Design: A retrospective cohort of 78 patients with stage II-III primary melanoma was analyzed using the NanoString assay to measure expression of 53 target genes, and MIP score was calculated. Statistical analysis correlating MIP with DSS, overall survival, distant metastatic recurrence, and distant metastasis-free interval was performed using ROC curves, Kaplan-Meier curves, and standard univariable and multivariable Cox proportional hazards models.Results: MIP significantly distinguished patients with distant metastatic recurrence from those without distant metastatic recurrence using ROC curve analysis (AUC ¼ 0.695; P ¼ 0.008). We defined high-and low-risk groups based on the cutoff defined by this ROC curve and find that MIP correlates with both DSS and overall survival by ROC curve analysis (AUC ¼ 0.719; P ¼ 0.004 and AUC ¼ 0.698; P ¼ 0.004, respectively). Univariable Cox regression reveals that a highrisk MIP score correlates with DSS (P ¼ 0.015; HR ¼ 3.2).Conclusions: MIP identifies patients with low risk of death from melanoma and may constitute a clinical tool to stratify patients with stage II-III melanoma for enrollment in clinical trials. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): Figure 4. MIP correlates with DMFI and DSS using Cox regression analysis. A, Univariable and multivariable Cox analysis of DMFI. B, Univariable and multivariable Cox analysis of DSS. Values are significant at P 0.05 ( Ã , P 0.05; ÃÃ , P 0.01; ÃÃÃ , P 0.001).Gartrell et al.

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Adjuvant Therapy for Melanoma

Cited by 26 publications

References 46 publications

A new era of proactive melanoma therapy: hit hard, hit early

A new era of proactive melanoma therapy: hit hard, hit early

Clinical Efficacy of a Novel Therapeutic Principle, Anakoinosis

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II–III Melanoma

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