What are the treatment options for Stage 3a melanoma (malignant melanoma)?

From the Guidelines

For patients with resected stage IIIA melanoma, adjuvant therapy with nivolumab, pembrolizumab, or dabrafenib plus trametinib for 52 weeks is recommended, as these options have shown significant improvement in recurrence-free survival 1. The treatment approach for stage 3a melanoma typically involves surgical removal of the primary tumor and affected lymph nodes, followed by adjuvant therapy to reduce recurrence risk. The standard surgical approach includes wide local excision of the primary tumor with appropriate margins and sentinel lymph node biopsy or complete lymph node dissection. After surgery, adjuvant therapy options include:

• Immunotherapy with checkpoint inhibitors such as pembrolizumab (Keytruda) or nivolumab (Opdivo), typically administered intravenously every 2-6 weeks for about one year.
• For BRAF-mutated melanomas, targeted therapy combinations like dabrafenib (Tafinlar) plus trametinib (Mekinist) may be used. Regular follow-up appointments are essential, typically every 3-6 months for the first few years, including physical examinations, imaging studies, and blood tests to monitor for recurrence. Side effect management is crucial, as immunotherapies can cause immune-related adverse events affecting various organ systems, while targeted therapies may cause fever, fatigue, and skin reactions. The treatment approach is personalized based on specific tumor characteristics, patient health status, and potential side effects, as noted in the guidelines 1. It is also important to consider the patient's individual risk-benefit quotient, especially for those with stage IIIA disease and microscopic sentinel nodal metastasis <1 mm diameter, who may have a good prognosis and low risk of relapse 1.

From the FDA Drug Label

The efficacy of KEYTRUDA was investigated in KEYNOTE-054 (NCT02362594), a multicenter, randomized (1:1), double-blind, placebo-controlled trial in patients with completely resected Stage IIIA (>1 mm lymph node metastasis), IIIB, or IIIC melanoma Patients were randomized to KEYTRUDA 200 mg intravenously every three weeks or placebo for up to one year until disease recurrence or unacceptable toxicity. The major efficacy outcome measure was investigator-assessed recurrence-free survival (RFS) in the whole population and in the population with PD-L1 positive tumors where RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant metastasis) or death, whichever occurs first The trial demonstrated a statistically significant improvement in RFS and DMFS for patients randomized to the KEYTRUDA arm compared with placebo.

• Stage 3a melanoma treatment: Pembrolizumab (KEYTRUDA) is a treatment option for patients with completely resected Stage IIIA melanoma.
• Key findings: The KEYNOTE-054 trial showed that pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) compared to placebo in patients with resected Stage III melanoma, including those with Stage IIIA disease 2.
• Treatment regimen: Pembrolizumab 200 mg intravenously every three weeks for up to one year until disease recurrence or unacceptable toxicity.

From the Research

Stage 3a Melanoma Treatment

• The treatment of stage III melanoma has been revolutionized in recent years by the introduction of immunotherapy and targeted therapy 3.
• Surgery remains a cornerstone for diagnosis and treatment of primary melanoma, but its role is being redefined with the emergence of new medical treatment options 3, 4.
• Neoadjuvant therapy is currently being investigated in several trials, and it has shown promising results in patients with resectable stage III or IV melanoma 5.
• Adjuvant therapies, including immune checkpoint inhibitors and molecular-targeted agents, are available for postoperative patients with stage IIB, IIC, and III melanomas 4.
• The need for invasive surgical procedures is being reduced with the invention of effective adjuvant and neoadjuvant therapies, and novel clinical trial data on regional lymph node dissection 4.

Surgical Procedures

• Wide excision margins are evidence-based, but not for all situations, and the recommended margins have changed over time 6.
• Sentinel lymph node biopsy provides relevant information for melanoma staging and is consistently recommended for melanomas >1-4 mm 6.
• Complete lymph node dissection has high morbidity and no impact on survival, and is restricted to regional control for clinically detected metastasis 6.

Immunotherapy

• Pembrolizumab and nivolumab are PD-1 inhibitors that have shown clinical efficacy in the treatment of metastatic melanoma 7.
• These immunotherapies have acceptable toxicity profiles, with most treatment-related adverse events being mild and manageable 7.
• Pembrolizumab and nivolumab are effective therapies in ipilimumab-refractory metastatic melanoma and present an overall favorable toxicity profile 7.