Updates in Pharmacotherapy for Melanoma

Angie Amado, PharmD Candidate 2019; Sonia Amin Thomas (Sonia Patel), PharmD, BCOP

Disclosures

US Pharmacist. 2018;43(6):HS2-HS9. 

In This Article

Nivolumab

Cancer cells may develop the ability to escape immunosurveillance (the body's ability to identify and destroy malignant cells). Checkpoint immunotherapies help increase immune response to circumvent these evasion mechanisms.[9–11] Monoclonal antibodies against the immune checkpoint receptor programmed cell death protein 1 (PD-1), such as nivolumab (Opdivo), prevent the receptor-ligand interaction on tumor cells, allowing T-cell activation and adequate immune response.[12] Nivolumab, a human immunoglobulin G4 (IgG4) and PD-1 inhibitor, is recommended by the National Comprehensive Cancer Network (NCCN) as first-line therapy for unresectable and metastatic melanoma (category 1).[5]

The efficacy of nivolumab in previously untreated unresectable stage III or IV melanoma was investigated in two phase III clinical trials. In CheckMate-066, nivolumab improved response rate, progression-free survival (PFS), and overall survival (OS) compared with chemotherapy, and percentages of grade 3 and 4 adverse effects (AEs) were lower for nivolumab versus chemotherapy.[13] CheckMate-067 was a randomized, double-blind, phase III study that compared nivolumab alone or with ipilimumab versus ipilimumab alone in patients with metastatic melanoma.[14] In this trial, nivolumab monotherapy improved response rates and PFS compared with single-agent ipilimumab, and it was associated with lower toxicity.[14] Both trials demonstrated that, in the first-line setting, nivolumab is a better option than chemotherapy or ipilimumab for patients with unresectable or metastatic disease.

Nivolumab was recently approved for a supplemental Biologics License Application to update the dosing schedule to include 480 mg infused every 4 weeks for a majority of approved indications, in addition to the already available option of 240 mg every 2 weeks.[15] Significant toxicities—which are immune-mediated because of the drug's mechanism of action—include hypothyroidism or hyperthyroidism, pneumonitis, nephritis, hepatitis, endocrinopathies, and pituitary disorders.[16] Although the frequency of grade 3 and 4 AEs requiring management is lower with anti–PD-1 monotherapy than with ipilimumabcontaining regimens, AE management involves withholding or discontinuing treatment and administering systemic corticosteroids.[5]

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