New Drug Extends Lives of Melanoma Patients

Study Shows Ipilimumab Helps Immune System Fight Deadly Skin Cancer

Medically Reviewed by Laura J. Martin, MD on June 07, 2010
From the WebMD Archives

June 7, 2010 (Chicago) -- A new drug that revs up the immune system to attack cancer cells extended the lives of people with advanced melanoma by an average of nearly four months in late-stage testing.

That may not sound like much, but given that "average survival [for metastatic melanoma] is six to nine months, on average, an additional four months is a very large difference for these patients," says one of the study's leaders, Steven O'Day, MD. He is director of the melanoma program at the Angeles Clinic and Research Institute in Los Angeles.

It's the first time any treatment has been shown to improve survival times in metastatic melanoma patients in rigorous late-stage clinical testing, he says.

O'Day presented findings on the drug, called ipilimumab, at the annual meeting of the American Society of Clinical Oncology (ASCO). They were simultaneously published in the June 5 online issue of the New England Journal of Medicine.

Melanoma is the deadliest type of skin cancer and is expected to take the lives of about 8,700 Americans this year. It is treatable if caught early, but once it spreads (metastasizes), it is rarely cured and typically kills within a year.

Patients have few treatment options. Chemotherapy drugs used to treat advanced melanoma shrink only about 15% of tumors. Interleukin-2 (IL-2), the standard treatment, stimulates the immune system to attack and kill cancer cells. Tumors shrink in one in four patients with advanced melanoma who get this treatment, but only about 6% to 11% live for five years.

As a result, researchers have been searching for new options. At last year's ASCO meeting, researchers reported that a vaccine known as gp100 that trains the immune system to seek out and attack cancer cells appeared to extend the time until cancer progressed.

Ipilimumab is a human monoclonal antibody that targets a molecule called CTLA-4 on the surface of T-cells. CTLA-4 acts like a brake to the immune system. Blocking the brake with ipilimumab unleashes the T-cells so they can go out and attack cancer cells, O'Day explains.

Ipilimumab Effective, but Not Benign

Previous research suggested that gp100 vaccine and ipilimumab act synergistically to fight tumors.

So for this study, the researchers assigned 676 patients at 125 centers around the world to one of three treatment groups: ipilimumab plus the gp100 vaccine; ipilimumab alone; or gp100 alone. All patients had failed to be helped by previous treatment.

Results showed that people who got ipilimumab alone lived an average of 10.1 months vs. 6.4 months for those who got gp100 alone. This corresponds to a 68% improvement in survival time.

"The addition of the gp100 vaccine [to ipilimumab] did not improve survival, but also did not increase side effects," O'Day says.

More importantly, 45.6% of people who took ipilimumab were alive after one year vs. 25.3% in the vaccine group, he says. At two years, the figures were 24% and 14%, respectively.

The drug, which is given as a 90-minute infusion every three weeks for four months, was hard for many patents to tolerate and even caused some deaths.

Serious immune-related reactions such as rash and colitis occurred in 10% to 15% of ipilimumab-treated patients compared with 3% on gp100 alone. Fourteen patients (2.1%) in the study died because of reactions to the treatment, seven from immune system problems.

Ipilimumab for Metastatic Melanoma

Nevertheless, melanoma doctors who heard the results here say they are enthusiastic about the new option.

"The prognosis for metastatic melanoma is really grim," says Patrick Hwu, MD, chief of the melanoma department at the University of Texas M.D. Anderson Cancer Center in Houston.

"A small subset of patients who get this drug will do well, living over five years," he says.

Since it is toxic, the challenge is to figure out which patients will benefit most, Hwu says.

Researchers are working to find biomarkers to guide treatment choices, he tells WebMD.

Doctors are most excited about the possibility of combining ipilimumab with experimental targeted drugs called BRAF inhibitors that show promise in early studies, Hwu says.

You could take the brakes off the immune system with ipilimumab and add extra gas with the BRAF inhibitors, he says.

Bristol-Myers Squibb, which makes ipilimumab and funded the work, plans to file an application for FDA approval later this year. No price has been set.

In the meantime, the drug is available "on a compassionate basis" at many medical centers nationwide, so some patients may be able to get access to it, O'Day says.

Show Sources


American Society of Clinical Oncology Annual Meeting 2010, Chicago, June 4-8, 2010.

Steven O'Day, MD, director, melanoma program, Angeles Clinic and Research Institute, Los Angeles.

Patrick Hwu, MD, chair, melanoma department, University of Texas M.D. Anderson Cancer Center, Houston.

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