What are the treatment options for melanoma (malignant melanoma)?

From the Guidelines

Treatment of melanoma should prioritize surgical excision with appropriate margins, followed by consideration of targeted therapies, immunotherapies, and radiation therapy based on the cancer's stage, genetic profile, and patient's overall health. For early-stage melanoma, surgical excision with margins of 0.5-2 cm depending on tumor thickness is the primary treatment, as supported by studies such as 1. In cases of metastatic melanoma, particularly for patients with BRAF wild-type unresectable/metastatic cutaneous melanoma, options like ipilimumab plus nivolumab followed by nivolumab, nivolumab, or pembrolizumab are recommended, as indicated by 1. The choice of treatment is also influenced by the patient's genetic profile, with BRAF inhibitors (dabrafenib, vemurafenib) combined with MEK inhibitors (trametinib, cobimetinib) being used for patients with BRAF mutations. Immunotherapy options, including checkpoint inhibitors such as pembrolizumab, nivolumab, and ipilimumab, are crucial for activating the immune system against cancer cells, typically administered intravenously every 2-6 weeks for up to two years. Radiation therapy may be utilized for symptom control or after surgery in high-risk areas. Regular follow-up with skin examinations, imaging studies, and blood tests is essential to monitor for recurrence, emphasizing the importance of early detection and treatment in improving outcomes, as melanoma can spread rapidly if left untreated, as discussed in 1, 1, and 1. Key considerations include the cancer's genetic profile, stage, location, and the patient's overall health, guiding the selection of the most appropriate treatment approach.

From the FDA Drug Label

CHECKMATE-76K (NCT04099251) was a randomized, double-blind trial in 790 patients with completely resected Stage IIB/C melanoma. Patients were randomized (2:1) to receive OPDIVO 480 mg or placebo by intravenous infusion every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity CHECKMATE-76K demonstrated a statistically significant improvement in RFS for patients randomized to the OPDIVO arm compared with the placebo arm.

CHECKMATE-238 (NCT02388906) was a randomized, double-blind trial in 906 patients with completely resected Stage IIIB/C or Stage IV melanoma Patients were randomized (1:1) to receive OPDIVO 3 mg/kg by intravenous infusion every 2 weeks or ipilimumab 10 mg/kg intravenously every 3 weeks for 4 doses then every 12 weeks beginning at Week 24 for up to 1 year. CHECKMATE-238 demonstrated a statistically significant improvement in RFS for patients randomized to the OPDIVO arm compared with the ipilimumab 10 mg/kg arm.

Treatment of Melanoma:

• Nivolumab (OPDIVO) is used for the treatment of melanoma.
• The recommended dose is 480 mg by intravenous infusion every 4 weeks for up to 1 year or until disease recurrence or unacceptable toxicity 2.
• Alternative dosing is 3 mg/kg by intravenous infusion every 2 weeks 2.
• Efficacy was demonstrated in CHECKMATE-76K and CHECKMATE-238 trials, showing statistically significant improvement in recurrence-free survival (RFS) for patients randomized to the OPDIVO arm compared with the placebo arm or ipilimumab 10 mg/kg arm, respectively 2.

From the Research

Treatment Options for Melanoma

• Surgical management is a key treatment modality for melanoma, with wide excision of the primary site and sentinel lymph node biopsy for selected patients being the standard approach for early-stage disease 3, 4.
• The surgical management of melanoma involves a balance of maximizing oncological outcome while minimizing morbidity, with wide excision with 1-2 cm margins depending on the depth of the tumor 3.
• Sentinel lymph node biopsy is indicated for patients with clinically node-negative, intermediate-thickness primary melanomas, and should also be considered in selected patients with thin and thick primaries 3.

Adjuvant Therapies

• Adjuvant therapies, such as anti-PD-1 agents (pembrolizumab and nivolumab), have been approved to mitigate the risk of recurrence in patients with resected stage III or IV melanoma 5.
• Pembrolizumab and nivolumab have comparable safety and efficacy profiles, and are generally offered to patients with resected stage IIIb-IV melanoma regardless of BRAF mutation status 5.

Immunotherapies

• PD-1 inhibitors, such as pembrolizumab and nivolumab, are novel immunotherapies that have been approved for the treatment of unresectable or metastatic melanoma in treatment-refractory patients 6.
• These inhibitors have demonstrated objective response rates of 26-38% and 31-40%, respectively, and acceptable toxicity profiles in clinical trials 6.

Current Surgical Management

• Surgery still plays an important role in treating early-stage melanoma, accurately determining the disease stage, and effective palliative treatment for advanced melanoma 7.
• The need for invasive surgical procedures will be reduced with the invention of effective adjuvant and neoadjuvant therapies, and novel clinical trial data on regional lymph node dissection 7.