Adjuvant and Neoadjuvant Therapy in Melanoma - Rodabe N. Amaria, MD
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This document discusses adjuvant and neoadjuvant therapy options for melanoma. Adjuvant therapy is given after surgery to lower the risk of recurrence, while neoadjuvant therapy is given before surgery. FDA-approved adjuvant therapies include interferon-alpha, pegylated interferon, and high-dose ipilimumab. Ongoing clinical trials are testing newer agents like BRAF/MEK inhibitors and anti-PD-1 antibodies in the adjuvant setting. Neoadjuvant therapy may help shrink tumors before surgery. Clinical trials are exploring neoadjuvant targeted therapies and immunotherapies and have shown potential for improved outcomes over standard surgery alone.
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Adjuvant and Neoadjuvant Therapy in Melanoma - Rodabe N. Amaria, MD
- 1. Adjuvant and Neoadjuvant Therapy in Melanoma R. Amaria, MD Assistant Professor, Melanoma Medical Oncology May 6, 2017
- 4. Brief Overview of Melanoma Staging • Stage I – Melanoma is thin – Hasn’t spread to lymph nodes – Prognosis is excellent with surgery alone • Stage III – The tumor can be any thickness and could be ulcerated – Has spread to lymph nodes or made a satellite (cancer cells near by the primary tumor) – Medical therapy may be indicated either before or after surgery depending on the amount of disease • IIIA: 1‐2 lymph nodes with small amount of disease • IIIB: 2‐3 lymph nodes with small disease,1 large lymph node, in‐ transit disease without nodes • IIIC: 4 or more lymph nodes, in‐ transit disease with lymph nodes • Stage II – Tumor is thicker and could be ulcerated – Hasn’t spread to lymph nodes – Prognosis with surgery is good • Stage IV – Cancer cells have left the skin and traveled to a distant site – Medical therapy with or without surgery/radiation
- 5. Ideal Adjuvant Therapy • Effective in destroying microscopic deposits of melanoma that could potentially be present after surgery – Allowing these melanoma deposits to grow will lead to melanoma recurrence • Has limited or easily manageable toxicity • To date, all FDA approved adjuvant therapies are immunotherapies designed to have our soldiers of the immune system (T cells) recognize and destroy melanoma
- 7. FDA Approved Adjuvant Therapy • Interferon‐α – FDA‐approved (1996) for Thick (> 4 mm) Primary/(+) LN – 5 days/week IV X 1 month, then three times a week SQ X 11 months – Virtually all patients experience toxicity – Benefit: CONTROVERSIAL • Delays relapse in about 10% of patients • Initial survival benefit non‐significant with additional follow‐up, and not confirmed in additional trials • Pegylated Interferon‐α – FDA‐approved (2011) for stage III melanoma – Administered as a weekly shot for up to 5 years – Delays relapse by about 9 months but no improvement in survival – Benefit: CONTROVERSIAL Kirkwood et al. Clin Can Res 2004; 10: 1670‐7
- 8. Adjuvant High Dose Ipilimumab Patients with Surgically Removed Stage IIIa‐IIIc melanoma Ipilimumab 10mg/kg Placebo Placebo Ipilimumab 5 year Recurrence Free Survival Rate 30.3% 40.8% 5 year Overall Survival Rate 54.4% 65.4% Immune‐Related Adverse Event Rate 2.7% 41.6% Eggermont et al. Lancet Oncol 2015; 16: 522‐30; Eggermont et al. N Engl J Med 2016
- 10. FDA Approved Adjuvant Therapy • High Dose Ipilimumab – FDA approved as of October 2015 for adjuvant therapy for Stage III cutaneous melanoma after surgery – 10% increased chance of delaying relapse by 9 months – 11% overall survival improvement – High side effect rate prohibits widespread use of this drug
- 15. Other Adjuvant Trials using Anti PD‐1 antibody • Nivolumab vs. High Dose Ipilimumab – Resected Stage IIIB/IIIC – Results expected Fall 2018 • Pembrolizumab vs. placebo – Resected Stage IIIA‐IIIC – Results expected Winter 2018
- 18. Ideal Neoadjuvant Therapy • Effective in shrinking down tumor rapidly • Has easily manageable or predictable toxicity profile • Facilitates understanding of mechanisms of response to therapy googleimages.com Clinically detectable lymph node Satellite/in‐transit metastasis
- 24. Patients with stage IIIB/IIIC or oligometastatic stage IV (≤3 lesions) Blood draw and tumor biopsy Pre-treatment Blood draw and tumor harvested at surgery Restaging CT scans every 12 weeks n=20 n=20 Arm A Neoadjuvant Nivolumab (4 doses) Restaging via CTs followed by surgical resection On treatment biopsy / blood draw (prior to dose 2 and dose 3) Adjuvant Nivolumab x 6 months Pathologic assessment with correlative studies Arm B Neoadjuvant Ipilimumab & Nivolumab (3 doses) Restaging via CTs followed by surgical resection Adjuvant Nivolumab x 6 months Follow up Follow up Neoadjuvant Immunotherapy Clinical Trial