Stage III melanoma means the cancer has spread beyond the original tumor to nearby areas but hasn’t reached distant parts of the body. The prognosis for Stage III melanoma varies depending on several factors, including the extent of lymph node involvement, the presence of in-transit or satellite lesions, and the patient’s overall health. Treatment for stage III melanoma, usually involves surgery and may include additional therapies like immunotherapy or targeted therapy to help prevent the cancer from coming back.
For patients with stage III melanoma that can be surgically removed (resectable), the usual treatment involves removing the affected lymph nodes and then providing additional therapy. This additional therapy, called adjuvant therapy, typically includes drugs like nivolumab or pembrolizumab for those without a BRAF mutation, or dabrafenib and trametinib for those with a BRAF mutation. Unfortunately, nearly 50% of patients treated this way still see their cancer return.
Background of the NADINA Trial
The NADINA trial, which was, recently presented at the 2024 ASCO Annual Meeting, demonstrated that neoadjuvant (before surgery) treatment with a combination of nivolumab and ipilimumab significantly improves outcomes for patients with stage III melanoma.
Rationale for the NADINA Trial
- Neoadjuvant ipilimumab with nivolumab results in higher pathological response and event free survival
- Reduced dosing of these drugs increased safety but still preserved its efficacy
- Patients with a major response have the potential for excellent long-term outcomes without additional therapy
Study Design and Methods:
- Participants: 423 patients with stage III melanoma, including types that were palpable, PET-positive, or visible on imaging, and had at least one confirmed lymph node metastasis.
- Study Design: Patients were divided into two groups.
- Group 1 received the standard treatment: lymph node removal followed by 12 monthly cycles of nivolumab.
- Group 2 received two cycles of nivolumab and ipilimumab before surgery, followed by lymph node removal. If their cancer didn’t respond well to the initial treatment, they received more therapy: nivolumab for those without a BRAF mutation, or dabrafenib/trametinib for those with a BRAF mutation.
Key Results:
- Event-Free Survival (EFS): Patients who started treatment with nivolumab and ipilimumab before surgery had better outcomes. For those with BRAF-mutant melanoma, the EFS was 83.5% compared to 52.1% for those who only received post-surgery therapy. For BRAF wild-type melanoma, the EFS was 83.9% compared to 62.4%.
- Pathological Response: About 56.6% to 59.0% of patients had a major pathologic response (MPR), meaning a significant reduction in cancer detected in their tissues. The complete response rates were around 45.8% to 47.2%.
- Safety and Quality of Life: There were more severe side effects in the group that received neoadjuvant therapy (29.7% vs. 14.7%), but the overall quality of life was similar between both groups.
Implications for Clinical Practice:
The NADINA trial shows that nearly 60% of patients only needed 6 weeks of treatment and all the subgroups benefited from the combination of therapies. That means many things for both patients and healthcare providers.
For patients and Caregivers:
- Enhanced Treatment Efficacy: The trial demonstrates how well a new or modified treatment performs compared to existing options, potentially offering more effective solutions for patients.
- Long-Term Outcomes: Results indicate the treatment improves long-term outcomes, such as survival rates or quality of life, which is crucial for patient prognosis and planning.
- Improved quality of life: Results are significant because they offer the potential for improved quality of life for patients. The reduced need for long term treatment, leads to a more manageable and less disruptive treatment experience, allowing patients to maintain better overall well-being and enjoy a higher quality of life throughout their treatment journey.
For Healthcare Providers:
- Future Treatment Guidelines: Positive results can influence future clinical guidelines and standard practices, ultimately benefiting a broader patient population through updated, evidence-based treatments.
The NADINA trial is the first phase 3 study to compare neoadjuvant immunotherapy to the standard of care (SOC) in melanoma. It is also the first phase 3 oncology trial to evaluate a neoadjuvant regimen consisting solely of immunotherapy. The trial found that using neoadjuvant ipilimumab plus nivolumab, followed by response-driven adjuvant treatment, significantly improves event-free survival (EFS) compared to adjuvant nivolumab alone. This suggests that neoadjuvant ipilimumab and nivolumab should be considered a new standard of care for patients with macroscopic stage III melanoma.
About the Author
Dr. Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. With his many years of experience, he brings a wealth of expertise to the complex and challenging world of oncology. About Dr Thomas – MedOncMD