FIRST AND ONLY TREATMENT TO EXTEND SURVIVAL FOR PEOPLE WITH METASTATIC MELANOMA, THE MOST DEADLY FORM OF SKIN CANCER, APPROVED IN CANADA
Melanoma one of fastest growing cancers in Canada
The approval by Health Canada of YERVOYTM (ipilimumab) is welcome news for Canadians with the deadliest form of skin cancer, metastatic melanoma, who are fighting to live longer. Yervoy, a cancer immunotherapy, is the first and only treatment approved for advanced melanoma in Canada that has been proven to extend survival in a phase three trial. Yervoy (3 mg/kg) is indicated for the treatment of unresectable or metastatic melanoma in patients who have failed or do not tolerate other systemic therapy for advanced disease.
Melanoma is one of the fastest growing cancers in Canada and the second most common cancer in young adults aged 15 to 34. The incidence has more than tripled over the last 30 years and continues to increase. An estimated 5,500 Canadians will be diagnosed with melanoma this year and 950 will die from it. Advanced melanoma cases represent 15 per cent of new melanoma patients in Canada. It is estimated that 1,200 Canadians are living with unresectable melanoma. Melanoma is responsible for 75 per cent of the deaths associated with skin cancer.
Demonstrated longer survival with Yervoy
In a pivotal randomized phase three clinical study, the median overall survival was 10 months for Yervoy and six months for the comparator treatment, a peptide vaccine (gp100).
Furthermore, the Kaplan-Meier estimated survival rate with Yervoy at both one and two years was almost doubled when measured against patients treated with gp100, 46 per cent versus 25 per cent at one year and 24 per cent versus 14 per cent at two years. Yervoy also showed long-term survival with some patients alive at three and four years.
The types of adverse events (AEs) attributed to Yervoy are generally related to its mechanism of action, i.e., immune-based. Immune-mediated adverse reactions, sometimes fatal, include enterocolitis, intestinal perforation, hepatitis, dermatitis, neuropathy, endocrinopathy as well as toxicity in other organ systems. Adverse events associated with Yervoy are managed by the administration of systemic corticosteroids, dose discontinuation and/or the use of other immunosuppressants.
“Once diagnosed with metastatic melanoma, a patient’s average life expectancy is about three to 18 months, depending upon the extent and location of disease. This dismal prognosis has not changed in over 40 years. With approval of Yervoy we now have the chance to offer some patients with advanced melanoma real hope for long-term survival,” said Dr. David Hogg, a medical oncologist with a large melanoma practice in Toronto. “With its unique mode of action, it is also an important step forward in the use of immunotherapy to treat cancer. It activates a patient’s own immune system to better identify and kill the melanoma cells.”
Mode of action
Unlike traditional chemotherapy, Yervoy indirectly targets the tumour by stimulating the patient’s immune system to recognize and destroy melanoma cells. Yervoy specifically blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which plays a role in suppressing the normal immune response. Yervoy blocks that suppression to allow the immune system to respond to melanoma cancer cells.
Also unlike most other medicines for advanced cancer, which are commonly given until the disease progresses, a complete course of treatment with Yervoy includes four infusions over a three-month period. Patients receive Yervoy every three weeks for four doses.
Last year, Derek Mason of Belleville, Ontario, was considered to be in the final stages of melanoma when his doctor was able to enroll him in a clinical trial with Yervoy. “Last year during my battle with melanoma I wasn’t expecting to reach my 40th birthday or celebrate Christmas, but I did,” Mason said. “Thanks to Yervoy, I am seeing progress and the melanoma, which had spread to many parts of my body, is regressing. I’m so thankful for my much improved condition. I’m living each day to the fullest, enjoying time with my wife and three young daughters.”
Kathy Barnard, founder of Save Your Skin Foundation, a group dedicated to raising awareness about skin cancer, providing information about treatment options and funding research, said, “It’s heartbreaking to see so many Canadians losing their battle with melanoma and, given that most patients with advanced melanoma survive less than a year, time is critical. My wish is for all Canadians who need it to have access to Yervoy as soon as possible to give them a chance to survive this disease.”
Bristol-Myers Squibb Canada (BMS Canada) is working with federal, provincial and territorial authorities to ensure patients in Canada will have access to Yervoy through provincial and private drug plans as quickly as possible.
BMS Canada is committed to making Yervoy available to previously treated patients who meet specific eligibility requirements through the BMS Canada Access to Hope patient assistance program.
“Melanoma is growing fastest in young adults and prevention is vital because 90 per cent of melanomas are caused by exposure to UV light and sunlight, including tanning beds,” said Annette Cyr, Chair of the Melanoma Network of Canada. “We are so pleased that the approval of Yervoy in Canada will provide a treatment option that can potentially extend survival of people who receive this terrible diagnosis. We also hope that this will encourage governments to make melanoma a priority.”
“The Canadian Dermatology Association is committed to raising awareness of melanoma, and we encourage Canadians to take steps to protect their skin from this serious disease,” said Dr. Denise Wexler, President of the Canadian Dermatology Association. “Today’s approval is great news for patients with advanced melanoma and we welcome this new treatment option.”
Yervoy is the first compound from Bristol-Myers Squibb’s robust immuno-oncology pipeline, which includes a variety of other compounds with the potential to harness the patient’s immune system to fight cancer. The company is an important player in the fight against cancer. It provided its first anti-cancer medication to Canadians more than four decades ago and continues to invest in research and development to respond to critical needs.
Melanoma is a rare but deadly form of skin cancer. It is characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Unlike many cancers, melanoma is clearly visible on the skin. Ninety per cent of melanomas are caused by exposure to UV light, including tanning beds.
Metastatic melanoma occurs when cancer spreads beyond the surface of the skin to other organs, such as the lymph nodes, lungs, brain or other areas of the body. Unresectable melanoma is a melanoma that cannot be removed or resected by surgery. The survival rate for melanoma is high if it is detected early but the advanced form, metastatic melanoma, is an aggressive disease which, until now, was characterized by high mortality.
The total direct and indirect cost of skin cancer in Canada in 2004 was estimated at $531.75 million, of which more than 80 per cent ($443.48 million) was from malignant melanoma.
Yervoy is a recombinant, human monoclonal antibody and the first approved cancer immunotherapy for melanoma to target the CTLA-4 (cytotoxic T lymphocyte-associated antigen-4), which plays a role in suppressing normal immune function.
Yervoy was approved by the United States Food and Drug Administration on March 25, 2011, and by the drug regulatory bodies of the European Union and Australia in July 2011.
In a pivotal randomized phase three clinical study, published in The New England Journal of Medicine, 676 patients in the study had all undergone previous treatment. The median overall survival was 10 months (95 per cent CI: 8.0-13.8) for Yervoy, six months (95 per cent CI: 5.5-8.7) for the comparator treatment (gp100) and 10 months (95 per cent CI: 8.5-11.5) for Yervoy + gp100, with p-values of 0.0026 (not adjusted for multiple comparisons) for Yervoy and 0.0004 for Yervoy + gp100 vs. gp100, respectively. The Kaplan-Meier estimated survival rate at one year was 46 per cent (95 per cent CI: 37.0, 54.1) in the Yervoy arm vs. 25 per cent (95 per cent CI: 18.1, 32.9) in the gp100 arm. The estimated survival rate at two years was 24 per cent (95 per cent CI: 16.0, 31.5) in the Yervoy arm vs. 14 per cent (95 per cent CI: 8.0, 20.0) in the gp100 arm. In the study, Yervoy showed long-term survival with some patients alive at three and four years.
Early diagnosis and appropriate management are essential to minimize life-threatening complications. Signs and symptoms suggestive of immune-mediated adverse reactions may be non-specific and should be considered Yervoy-related, unless an alternate etiology is identified. Most immune-mediated adverse reactions occurred during the treatment period; however, onset months after the last dose of Yervoy has also been reported.
In the phase three study, the most common adverse reactions were diarrhea (27 per cent), rash (26 per cent), pruritus (26 per cent), fatigue (24 per cent), nausea (23 per cent), vomiting (12 per cent), decreased appetite (11 per cent), and abdominal pain (11 per cent) for the Yervoy alone arm; diarrhea (29 per cent), rash (20 per cent), pruritus (18 per cent), fatigue (23 per cent), nausea (19 per cent), vomiting (9 per cent), decreased appetite (10 per cent), and abdominal pain (10 per cent) for gp100 arm. Ten per cent of patients treated with Yervoy and four per cent of patients treated with gp100 had to discontinue their therapy because of adverse reactions.
About Bristol-Myers Squibb Canada
Bristol-Myers Squibb Canada is an indirect wholly-owned subsidiary of Bristol-Myers Squibb Company, a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. Bristol-Myers Squibb Canada is a leading provider of medicines to fight cancer, cardiovascular and metabolic disorders, infectious diseases (including HIV/AIDS), nervous system diseases and serious mental illness. Bristol-Myers Squibb Canada's operations are headquartered in Montreal, Quebec.