Cancer successes are usually measured in months, not years. Large clinical trial on promising new treatments are celebrated when they show an average effect of a dozen weeks, and extension of life that can be measured in years is cause for rapture. So a new treatment that cuts down a high-risk cancer’s recurrence rate over a 2-year period by 20 percent is a major leap forward – even if the cancer is not among the most common types.
The cancer, in this case, is neuroblastoma, a tumor originating in nerve tissues outside the brain that predominantly strikes children under the age of 5. Though there are only 650 estimated new cases of neuroblastoma in the United States every year, that’s still enough for it to rank as the second most common solid tumor in children. While successful cures for low and intermediate-risk neuroblastoma cases have been found, roughly half of patients have a “high-risk” form of the disease that has only a 40 percent survival rate. That makes the new research, published today in the New England Journal of Medicine, the biggest advance in more than a decade for patients and families affected by the most deadly forms of the disease.
“Neuroblastoma is a rare pediatric cancer, but this is so, so, so, remarkable,” said Susan Cohn, professor of pediatrics at Comer Children’s Hospital and an author of the study. “To improve survival rates by 20 percent is fantastic.”
The treatment at the heart of the study is a form of immunotherapy, the drug strategy that seeks to recruit a patient’s native immune system to attack the tumor. An antibody against a protein expressed by tumor cells, called ch14.18, is the central prong of the three-drug therapy tested in the trial. Two other drugs, interleukin-2 and GM-CSF, are immune factors designed to help stimulate white blood cells to kill tumor cells. In the trial’s experimental group, this trio of drugs was added to the normal course of therapy for high-risk neuroblastoma, which includes surgery, chemotherapy, radiation, a transplant of the patient’s own stem cells to restore healthy blood cells, and retinoic acid.
Recruiting patients for the trial was a long and arduous process, Cohn said, due to concerns from patients’ families about trial randomization and side effects. Ten years of recruitment later, the study had enough power to be stopped — when analysis of the results showed an overwhelmingly positive effect of treatment, it was considered unethical to proceed. Patients in the control group were given the option of switching to the immunotherapy, and new patients were enrolled in a non-randomized trial to continue assessing long-term effects of the treatment.
Understanding the toxicity of the treatment is especially important, as the initial trial revealed a suite of side effects that accompanied the substantial benefits. Pain, reduced blood pressure, fluid in the lungs, and other adverse effects need to be closely watched by health professionals during the treatment, Cohn said.
“It’s not an easy therapy; there are lots of side effects and patients must be monitored carefully while they are receiving treatment in the hospital,” Cohn said. “If it hadn’t shown a clear advantage, we would no longer do it.”
Ongoing trials are collecting more data about the toxicities and the benefits of the immunotherapy. Currently, these clinical trials are the only way for a patient to receive the therapy, Cohn said, and the data will be used to hopefully obtain FDA approval in the future. If brought to market, the treatment would join a family of cancer immunotherapies that have shown recent success in treating adult colorectal cancer, breast cancer and leukemia such as Avastin and Herceptin. But none of those drugs were launched with results like those published for neuroblastoma treatment.
“Our study showed a 20 percent improvement in event-free survival,” Cohn said. “This is truly remarkable.”
[Another study published in this week's NEJM by the Children's Oncology Group including Cohn showed that reduced chemotherapy was successful in treating intermediate-risk neuroblastoma.]