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

Pembrolizumab

Pembrolizumab, another human IgG4 and PD-1 inhibitor, is in the same category as nivolumab and is also recommended by the NCCN as first-line therapy for unresectable and metastatic melanoma (category 1).[5] As with nivolumab, pembrolizumab has demonstrated improved response and PFS compared with chemotherapy or ipilimumab (monotherapy), and in clinical trials it has been associated with a lower risk of AEs in patients with unresectable stage III or IV metastatic disease.[25] The KEYNOTE-006 trial demonstrated that pembrolizumab results in improved OS compared with ipilimumab.[25]

The FDA-recommended dosage of pembrolizumab is 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity.[26] Although studies such as KEYNOTE-002 administered pembrolizumab for a maximum of 24 months,[27] it is common for patients to discontinue anti–PD-1 therapy earlier than that. Clinical experience with treatment beyond 1 year is limited, and further studies should be performed to determine whether lower-frequency maintenance therapy is sufficient to maintain longterm clinical benefit.[5] Currently, no data from prospective, randomized trials directly compare nivolumab and pembrolizumab, but these agents appear to have similar safety profiles. Labeling for both nivolumab and pembrolizumab includes specific warnings about pneumonitis and nephritis.[23,26] However, randomized clinical trials have shown that single-agent nivolumab and pembrolizumab are associated with less toxicity than ipilimumab monotherapy. Compared with ipilimumab, both anti–PD-1 immunotherapies were associated with notably less diarrhea and pruritus, but more hypothyroidism.[14,25] Endocrinopathies associated with ipilimumab are more difficult to manage and require hormone replacement therapy (HRT) in addition to corticosteroids.[5] Compared with other irAEs associated with ipilimumab, endocrinopathies were less likely to fully reverse and took longer to resolve.[28,29] Patients with endocrinopathies frequently required ongoing HRT, highlighting the importance of early detection to minimize long-term effects.

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