Interferon is Associated with Improved Survival for Node-Positive Cutaneous Melanoma: A Single-Institution Experience

Oliver, Daniel; Sondak, Vernon K.; Ström, T.; Zager, Jonathan S.; Naghavi, A.O.; Sarnaik, Amod; Messina, Jane L.; Caudell, Jimmy J.; Trotti, Andy; Torres-Roca, Javier F.; Harrison, Louis B.

doi:10.2217/mmt-2017-0025

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…Overall, the outcomes of 4 multicenter randomized controlled trials involving a total of 1916 patients supported the use of HDI as adjuvant therapy 25–27,47 . These studies demonstrated that HDI improved RFS in all 3 trials and overall survival (OS) in E1684 (compared with observation) and E1694 (vs. GMK) 29,30 . A subsequent meta-analysis, 29 of 14 randomized controlled trials of adjuvant IFN-α testing varying dose levels, regimens, and routes of administration indicated that adjuvant therapy with IFN-α reported a statistically significant improvement in both RFS and OS.…”

Section: Cytokine Immunotherapy: Interferon αmentioning

confidence: 97%

“…[25][26][27]47 These studies demonstrated that HDI improved RFS in all 3 trials and overall survival (OS) in E1684 (compared with observation) and E1694 (vs. GMK). 29,30 A subsequent meta-analysis, 29 of 14 randomized controlled trials of adjuvant IFN-α testing varying dose levels, regimens, and routes of administration indicated that adjuvant therapy with IFN-α reported a statistically significant improvement in both RFS and OS. However, the clinical benefit was found to be minor (the hazard ratios [HRs] for disease recurrence and death were 0.82 and 0.89, respectively).…”

Section: Cytokine Immunotherapy: Interferon αmentioning

confidence: 99%

“…High-dose interferon α2b (HDI) was the first adjuvant therapy to be approved in the United States in 1995, followed by pegylated interferon α (IFN-α) in 2011 and ipilimumab at 10 mg/kg (ipi10) in 2015 25–28 . However, the utilization of these agents has been limited, primarily due to poor tolerance and high toxicity rates 29,30 . Recent studies have supported the role of anti–programmed cell death protein 1 (PD-1) monoclonal antibodies, nivolumab and pembrolizumab, as adjuvant therapy.…”

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confidence: 99%

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Treatment of Stage III Resectable Melanoma—Adjuvant and Neoadjuvant Approaches

Tarhini,

Castellano,

Eljilany

2024

Cancer J

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Patients with stage III resectable melanoma carry a high risk of melanoma recurrence that ranges from approximately 40% to 90% at 5 years following surgical management alone. Postoperative systemic adjuvant therapy targets residual micrometastatic disease that could be the source of future recurrence and death from melanoma. Randomized phase III adjuvant trials reported significant improvements in overall survival with high-dose interferon α in 2 of 3 studies (compared with observation and GMK ganglioside vaccine) and with anti–cytotoxic T-lymphocyte antigen 4 ipilimumab at 10 mg/kg compared with placebo and ipilimumab 3 mg/kg compared with high-dose interferon α. In the modern era, more recent phase III trials demonstrated significant recurrence-free survival improvements with anti–programmed cell death protein 1, pembrolizumab, and BRAF-MEK inhibitor combination dabrafenib-trametinib (for BRAF mutant melanoma) versus placebo. Furthermore, anti–programmed cell death protein 1, nivolumab and pembrolizumab have both been shown to significantly improve recurrence-free survival as compared with ipilimumab 10 mg/kg. For melanoma patients with clinically or radiologically detectable locoregionally advanced disease, emerging data support an important role for preoperative systemic neoadjuvant therapy. Importantly, a recent cooperative group trial (S1801) reported superior event-free survival rates with neoadjuvant versus adjuvant therapy. Collectively, current data from neoadjuvant immunotherapy and targeted therapy trials support a future change in clinical practice in favor of neoadjuvant therapy for eligible melanoma patients.

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Section: Cytokine Immunotherapy: Interferon αmentioning

confidence: 97%

Section: Cytokine Immunotherapy: Interferon αmentioning

confidence: 99%

mentioning

confidence: 99%

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Treatment of Stage III Resectable Melanoma—Adjuvant and Neoadjuvant Approaches

Tarhini,

Castellano,

Eljilany

2024

Cancer J

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“…12–15 These adjuvant therapies provided improved survival benefit as compared with observation or placebo, however, high rates of toxicities were significant concerns. 16,17 Recent studies have supported the adjuvant use of anti-PD1 monoclonal antibodies nivolumab and pembrolizumab as well as the combination of dabrafenib and trametinib (in patients with stage III BRAF-mutated melanoma). 18–20 However, the relapse free survival for these patients is still poor, with median recurrence-free survival (RFS) of approximately 70–80% at year 1 and 50–60% at 3 years.…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant therapy of locally/regionally advanced melanoma

et al. 2019

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Locally/regionally advanced melanoma confers a major challenge in terms of surgical and medical management. Surgical treatment carries the risks of surgical morbidities and potential complications that could be lasting. In addition, these patients continue to have a high risk of relapse and death despite the use of standard adjuvant therapy. Neoadjuvant therapy has the potential to significantly improve the clinical outcome of these patients, particularly in this era of newer and effective targeted and immunotherapeutic agents. Previous neoadjuvant studies tested chemotherapy with temozolomide where the clinical activity was limited. Biochemotherapy (BCT) was tested in two studies in the neoadjuvant setting and showed high tumor response rates; however, BCT was ultimately abandoned following its failure to demonstrate survival benefits in randomized trials of metastatic disease. Success of immunotherapy and targeted therapy in prolonging the lives of patients with metastatic melanoma generated considerable interest to investigate these novel strategies in the adjuvant and neoadjuvant settings. A number of neoadjuvant targeted and immunotherapy studies have been completed in melanoma to date and have yielded promising clinical activity. Given these encouraging results, a number of studies with other molecularly targeted and immunotherapeutic agents and their combinations are ongoing in the neoadjuvant setting; long-term outcome data are eagerly awaited. Such studies also provide access to biospecimens before and during therapy, allowing for the conduct of biomarker and mechanistic studies that may have a significant impact in guiding adjuvant therapy choices and drug development.

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