Home > Dr. Ward's Newspaper Column Home > 2010
New treatment for skin cancer on the horizon
July 05, 2010This time of year, it is customary to talk about the skin cancer malignant melanoma. There are a couple of good reasons for this. First and foremost, it is summer time and the biggest risk factor for melanoma is sunburn. Second, beachwear is ideal for checking skin for funny-looking and changing moles. But there is another reason to talk about malignant melanoma during the summer.
Malignant melanoma is increasing in incidence faster than any other cancer, yet our search for effective treatment has been nothing short of a labyrinth of dark, dead end tunnels. Chemotherapy response rates are low and short lived. No treatment has ever shown a meaningful survival benefit in a randomized trial. And though, occasionally, individual patients may do well, only 25 percent of patients with stage four disease live more than one year, and only 10 percent will make it to two years. For the last decade, we have pinned our hopes on a melanoma vaccine. Some studies seemed to show promise, but the light at the end of that tunnel has faded. For other “hard-to-crack” cancers, we are being flooded with new drugs based on a greater understanding of the genetic genesis of malignancy. This is not the case for melanoma.
But at last month’s annual American Society of Clinical Oncology meeting, something occurred that has never happened before. A large, randomized, placebo controlled trial (the “holy grail” of clinical science) demonstrated a survival advantage. The drug is Ipilimumab, or ipi for short. It is a laboratory manufactured antibody against a protein called CTLA-4. This protein, found on a white blood cell called the T-cell, acts as a brake on the immune activity of the T-cell. Scientists hoped that if the brake was removed, the unimpeded T-cells would attack the malignant melanoma and change the course of the disease.
The result of a trial of 676 patients, all with stage four disease and already having failed a treatment, was that the average patient lived two months longer than those treated with a vaccine. It doesn’t sound like much, but the 30 percent that responded often had sustained responses, resulting in double the number of patients alive at one year anwd two years. And of 40 patients whose cancer recurred after responding well to an initial treatment, 70 percent of these patients also responded favorably to a second round of ipi therapy, suggesting that a strategy of repeat treatments may provide long term control for some patients. It is a grand slam in melanoma treatment.
Ipi is not without toxicities. When you turn the immune system on in an indiscriminate way, it can have unintended consequences. Among the consequences of turning the T-cells against the normal cells in the body are autoimmune disorders, such as colitis, which were were a significant problem for a minority of patients (seven patients died of autoimmune complications of the therapy). Luckily, judicious use of steroids controlled these problems in the vast majority without turning off the anti-cancer effect of the treatment.
The next steps are to get ipi to patients and improve the results in further clinical trials. Until the FDA approves ipi for commercial use, perhaps before the end of the year, it is being made available for those with no other treatment options at 75 centers in the United States, including three centers in Washington. Another drug, PLX4032, which targets a mutated gene found in about 40 percent of melanomas, has had some impressive results in early trials. Perhaps a partnering of ipi and this agent will bring us out of the dark labyrinth of malignant melanoma and into the sunshine... wearing sunscreen, of course.
Dr. Ward is a medical oncologist at Puget Sound Cancer Centers. He can be reached at (425) 775-1677.