by Dr. C.H. Weaver M.D. updated 5/2019
The US Food and Drug Administration (FDA) initially approved Yervoy™ (ipilimumab) for the treatment of melanoma that had spread to other sites or could not be surgically removed in 2011. Since then Yervoy's approval has expanded to all patients with advanced and earlier stage III disease. In addition Yervoy shows promise in the treatment of uveal-eye melanoma.
Yervoy® is a monoclonal antibody approved for the treatment of melanoma. Yervoy® targets a molecule known as CTLA4. CTLA4 is found on the surface of T cells and is thought to inhibit immune responses. By targeting this molecule, Yervoy® enhances the immune system’s response against tumor cells.
The initial phase III clinical trial that contributed to the approval of Yervoy involved 676 people with melanoma. All had melanoma that had stopped responding to other treatments and had spread or could not be surgically removed. Study participants were assigned to one of three treatment groups: 1) Yervoy plus an experimental anti-cancer vaccine (gp100); 2) Yervoy alone; or 3) the vaccine alone.
Overall survival was 10 months among patients treated with Yervoy (with or without the gp100 vaccine), compared with six months among patients treated with the gp100 vaccine alone. Survival at two years was 24% among patients treated with Yervoy alone and 14% among patients treated with the gp100 vaccine alone.
Severe autoimmune reactions occurred in 13% of patients treated with Yervoy. Patients who experience these reactions are advised to discontinue Yervoy and begin corticosteroid therapy. The company that will market Yervoy is collaborating with the FDA on a plan to inform healthcare providers and patients about the potential risks. This process is referred to as a Risk Evaluation and Mitigation Strategy (REMS).
Yervoy was the first new treatment approved for metastatic melanoma in more than a decade.
Yervoy in Stage III Melanoma
The first trial of the immunomodulator Yervoy® conducted in patients with stage III melanoma demonstrated an improvement by delaying cancer recurrence and improving survival.
Standard treatment for stage III melanoma typically involves surgery to remove the cancer. Because many patients will experience a recurrence following treatment with surgery alone, doctors have been searching for an appropriate therapy to be administered after surgery to improve outcomes.
In the current study a total of 951 patients over 18 years of age who underwent complete surgical removal of a stage III cutaneous melanoma were treated with either a placebo or Yervoy® and directly compared. Treatment with Yervoy®was every 3 weeks for 4 doses, then every 3 months for up to 3 years until completion, melanoma recurrence, or unacceptable toxicity.
At a median follow-up of 2.7 years from the initiation of this phase III trial, Yervoy® when utilized as adjuvant therapy both reduced the risk of melanoma recurrence and improved the duration of survival. Overall 46% of patients treated with Yervoy® were free of disease recurrence compared to 35% of patients treated with placebo. Patients survived without cancer recurrence an average of 26.1 months when treated with Yervoy® compared to only 17.1 months for placebo.
The demonstration that Yervoy® improves patient outcomes when used to treat stage III melanoma is the first significant advance in the management of earlier stage melanomas in years. Additional clinical trials will undoubtedly evaluate Yervoy® in stage II patients and explore combination with other novel melanoma therapies to see if outcomes can be further improved.
Richard Pazdur MD, director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research stated that “This new use of the drug in earlier stages of the disease builds on our understanding of the immune system’s interaction with cancer.”
Yervoy in Uveal Melanoma
The first trial of the immunomodulator Yervoy® conducted in patients with uveal melanoma appears promising in according to the results of a small clinical trial presented at the recent Society of Melanoma Research (SMR) 2014 International Congress, in Zurich, Switzerland.
Uveal melanoma is the most common cancer of the eye in adults, and the uvea is the second most common location for primary melanoma. Current treatment options are very limited and survival is poor due to early spread of the cancer to the liver.
Dr Piulats and colleagues treated 32 patients at 5 centers in Spain with progressive uveal melanoma that had not previously received any systemic therapy with Yervoy® given every 3 weeks for 4 doses, and then every 12 weeks until progression of melanoma, intolerance of the drug, or withdrawal from the trial.
After approximately 2 years of follow-up almost 25% of patients survive. The disease control rate was close to 50%, with stable disease seen in 39.7% and a partial response in 6.45%. There are few treatment options for individuals with uveal melanoma, and Yervoy®appears promising. This trial however was small and uncontrolled. Additional evaluation in appropriately designed studies with greater numbers of patients are required.
- J Clin Oncol 32:5s, 2014 (suppl; abstr LBA9008)
- Society of Melanoma Research (SMR) 2014 International Congress. The results that were reported in the poster presentation have been published in Pigment Cell Melanoma Research (Pigment Cell Melanoma Res 2014;27:1219).
- US Food and Drug Administration. FDA news release. FDA approved new treatment for a type of late-stage skin cancer. March 25, 2011.
- United States Food and Drug Administration. FDA News Release. FDA approves Yervoy to reduce the risk of melanoma returning after surgery. Available at: . Accessed October 29, 2015.
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