Dataset Information

Clinicopathological Features, Staging, and Current Approaches to Treatment in High-Risk Resectable Melanoma.

ABSTRACT: The incidence of melanoma in the United States has been increasing over the past several decades. Prognosis largely depends on disease stage, with 5-year melanoma-specific survival ranging from as high as 99% in patients with stage I disease to less than 10% for some patients with stage IV (distant metastatic) disease. Fortunately, in the last 5-10?years, there have been remarkable treatment advances for patients with high-risk resectable melanoma, including approval of targeted and immune checkpoint blockade therapies. In addition, results of recent clinical trials have confirmed the importance of sentinel lymph node biopsy and continue to refine the approach to regional lymph node basin management. Lastly, the melanoma staging system was revised in the eighth edition AJCC Cancer Staging Manual, which was implemented on January 1, 2018. Here we discuss these changes and the clinicopathological features that confer high risk for locoregional and distant disease relapse and poor survival. Implications regarding the management of melanoma in the metastatic and adjuvant settings are discussed, as are future directions for neoadjuvant therapies.

SUBMITTER: Keung EZ

PROVIDER: S-EPMC7492771 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clinicopathological Features, Staging, and Current Approaches to Treatment in High-Risk Resectable Melanoma.

Keung Emily Z EZ Gershenwald Jeffrey E JE

Journal of the National Cancer Institute 20200901 9

The incidence of melanoma in the United States has been increasing over the past several decades. Prognosis largely depends on disease stage, with 5-year melanoma-specific survival ranging from as high as 99% in patients with stage I disease to less than 10% for some patients with stage IV (distant metastatic) disease. Fortunately, in the last 5-10 years, there have been remarkable treatment advances for patients with high-risk resectable melanoma, including approval of targeted and immune check ...[more]

PMID: 32061122

Similar Datasets

Project description:ImportanceDespite the clear potential benefits of neoadjuvant therapy, the optimal neoadjuvant regimen for patients with high-risk resectable melanoma (HRRM) is not known.ObjectiveTo compare the safety and efficacy of dual checkpoint inhibitors with anti-programmed cell death protein-1 (anti-PD1) therapy in a neoadjuvant setting among patients with HRRM.Design, setting, and participantsIn this pooled analysis of clinical trials, studies were selected provided they investigated immune checkpoint inhibitor treatment, were published between January 2018 and March 2023, and were phase 1, 2, or 3 clinical trials. Participant data included in the analysis were derived from trials evaluating the efficacy and safety of anti-PD1 monotherapy and the combination of anti-cytotoxic T lymphocyte-associated protein-4 with anti-PD1 in the neoadjuvant setting, specifically among patients with HRRM.InterventionsPatients were treated with either anti-PD1 monotherapy; dual checkpoint inhibition (DCPI) with a conventional dose of 3-mg/kg ipilimumab and 1-mg/kg nivolumab; or DCPI with an alternative-dose regimen of 1-mg/kg ipilimumab and 3-mg/kg nivolumab.Main outcomes and measuresThe main outcomes were radiologic complete response (rCR), radiologic overall objective response (rOOR), and radiologic progressive disease. Also, pathologic complete response (pCR), the proportion of patients undergoing surgical resection, and occurrence of grade 3 or 4 immune-related adverse events (irAEs) were considered.ResultsAmong 573 patients enrolled in 6 clinical trials, neoadjuvant therapy with DCPI was associated with higher odds of achieving pCR compared with anti-PD1 monotherapy (odds ratio [OR], 3.16; P < .001). DCPI was associated with higher odds of grade 3 or 4 irAEs compared with anti-PD1 monotherapy (OR, 3.75; P < .001). When comparing the alternative-dose ipilimumab and nivolumab (IPI-NIVO) regimen with conventional-dose IPI-NIVO, no statistically significant difference in rCR, rOOR, radiologic progressive disease, or pCR was noted. However, the conventional-dose IPI-NIVO regimen was associated with increased grade 3 or 4 irAEs (OR, 4.76; P < .001). Conventional-dose IPI-NIVO was associated with greater odds of achieving improved rOOR (OR, 1.95; P = .046) and pCR (OR, 2.99; P < .001) compared with anti-PD1 monotherapy. The alternative dose of IPI-NIVO also was associated with higher odds of achieving rCR (OR, 2.55; P = .03) and pCR (OR, 3.87; P < .001) compared with anti-PD1 monotherapy. The risk for grade 3 or 4 irAEs is higher with both the conventional-dose (OR, 9.59; P < .001) and alternative-dose IPI-NIVO regimens (OR, 2.02; P = .02) compared with anti-PD1 monotherapy.Conclusion and relevanceIn this pooled analysis of 6 clinical trials, although DCPI was associated with increased likelihood of achieving pathological and radiologic responses, the associated risk for grade 3 or 4 irAEs was significantly lower with anti-PD1 monotherapy in the neoadjuvant setting for HRRM. Additionally, compared with alternative-dose IPI-NIVO, the conventional dose of IPI-NIVO was associated with increased risk for grade 3 or 4 irAEs, with no significant distinctions in radiologic or pathologic efficacy.

Dataset Information

Clinicopathological Features, Staging, and Current Approaches to Treatment in High-Risk Resectable Melanoma.

Publications

Clinicopathological Features, Staging, and Current Approaches to Treatment in High-Risk Resectable Melanoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets