Nivolumab in the treatment of malignant melanoma: Review of the literature

the ONA take:

Nivolumab (Opdivo) can become an alternative therapy for advanced malignant melanoma, according to a literature review published in the journal OncoTargets and Therapy.

Nivolumab is an IgG4 monoclonal antibody that binds to the PD-1 receptor and blocks its interactions with PD-1 ligands, PD-L1 and PD-L2, thereby releasing PD-1 pathway-mediated inhibition of the anti-tumor immune response. The immunotherapy is already approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma following disease progression after treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor, and metastatic squamous non-small cell lung cancer following progression on or after platinum-based chemotherapy.

Compared with dacarbazine, the objective response rate was 26.1% higher with nivolumab in patients with malignant melanoma without BRAF mutation. In patients unresponsive to ipilimumab, objective response rate for nivolumab was 31% versus 10.7% for dacarbazine or paclitaxel with carboplatin.

In regard to safety, the most common adverse reaction in patients with melanoma is rash. Health care professionals should be aware that immune-mediated adverse reactions may occur, and in those instances, corticosteroids may be administered based on the severity of the reaction.

OncoTargets and Therapy
OncoTargets and Therapy

Abstract: Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. When advanced melanoma patients were treated with nivolumab, median overall survival became longer. Overall survival rate was significantly better in nivolumab-treated melanoma patients than dacarbazine-treated melanoma patients. Nivolumab had an acceptable long-term tolerability profile, with 22% of patients experiencing grade 3 or 4 adverse events related to the drug. Therefore, nivolumab can become an alternative therapy for advanced malignant melanoma.


Keywords: monoclonal antibody, PD-1, PD-L1  

INTRODUCTION

Malignant melanoma is a melanocyte neoplasm that usually takes place in the skin and occasionally harbors mutations in genes including BRAF.1,2 Each year in the world, the number of estimated new cases of malignant melanoma is 132,000 and approximately 48,000 patients die from malignant melanoma. When malignant melanoma is diagnosed at the early stage (stage 0/I), 5-year survival rate is more than 90% after surgical excision. However, when malignant melanoma is overlooked, it tends to invade deeply and metastasize to lymph nodes and other organs. Median overall survival rate for melanoma patients with metastasis is less than 1 year.

For advanced melanoma, systemic therapy is usually needed; however, there were only limited options just a few years ago. There are a lot of patients who are resistant to conventional chemotherapies with an alkylating agent, dacarbazine, and interferon (IFN)-α.

There have been a lot of studies on development of novel therapies for unresectable malignant melanoma targeting immune checkpoint inhibitors.3,4 One of the recent advancements came from the new development of monoclonal antibody against an immune checkpoint inhibitor, programmed death receptor-1 (PD-1).5,6

Nivolumab was developed as a fully human IgG4 monoclonal antibody against PD-1, an immune checkpoint inhibitor that negatively controls T-cell proliferation and functions. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. This review focuses on the functional and molecular characteristics of PD-1 and the clinical efficacy and tolerability of its antibody, nivolumab.  

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