Patients with four types of cancer have new treatment options available after approval of three new drugs by the United States Food and Drug Administration in recent weeks.
The highly targeted drugs focus their firepower on specific types of cancer cells to treat groups of patients with non-small cell lung cancer, metastatic melanoma, Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL). They offer new options for late-stage patients after frontline treatments have failed.
All three drugs were available at MD Anderson via clinical trials before FDA approval.
"This is an ideal example of personalized therapy," says Faye Johnson, M.D., Ph.D., associate professor in Thoracic /Head and Neck Medical Oncology. "The drug is given only to a small group of patients with the target genetic variation in their tumors. It worked great and the toxicities are trivial, especially compared to chemotherapy."
While Johnson is talking about the drug crizotinib (known commercially as Xalkori®å), approved for advanced-stage non-small cell lung cancer patients whose tumors have the ALK gene fusion, the same can be said for the other two drugs.
Patients and oncologists say vemurafenib (Zelboraf®å), approved for metastatic melanoma patients whose tumors have the BRAF mutation, and brentuximab vedotin (Adcetris®å), which employs an antibody to deliver chemotherapy only to lymphoma cells, have similar effects.
Help for patients who are out of options
By attacking cancer cells based on unique aspects of their biology, the new drugs fulfill the promise of targeted therapy to allow more customized treatment for patients. They mark another move away from giving patients less-targeted chemotherapies that attack fast-growing cells in general, which also affects normal cells, causing side effects.
"About 20 percent of patients with Hodgkin lymphoma and upwards of 40 to 60 percent of patients with anaplastic large cell lymphoma can develop relapsed or refractory disease to front-line chemotherapy," says Michelle Fanale, M.D., assistant professor in Lymphoma and Myeloma. "Patients are typically recommended for additional chemotherapy and blood stem cell transplantation. In particular those patients with HL or ALCL who relapse after transplantation can have very limited treatment options."
The percentage of patients who had partial or complete shrinkage or disappearance of their disease ranged from 50-61 percent in the lung cancer trials to 73 percent for Hodgkin lymphoma and 86 percent for ALCL on the lymphoma trials, according to the FDA.
"All of our patients on the crizotinib trial had a response, ranging from the minor to the miraculous," Johnson said. About 5 percent of NSCLC patients have the ALK mutation in their tumors.
Count Atlanta investment executive Jeffrey Wigbels at the miraculous end of that spectrum. A non-smoker diagnosed with stage IV non-small cell lung cancer in October 2006, he has gone through six chemotherapy regimens along with four radiation treatments for metastasis.
Last October, he faced another recurrence that included a tumor in his throat that made it impossible to swallow. Wigbels said MD Anderson pathologist John Stewart, M.D., Ph.D., pushed to test his tumor for the ALK mutation and got him on Johnson's clinical trial.
"Five days after I took the first pill, a bunch of people came over to watch football. They ordered pizza," Wigbels recalls. "I said 'okay, that looks really good. ' I took a bite, and another bite, and by end of the night I had eaten a whole pizza."
"There's no sign of cancer now," he says.
Vemurafenib for metastatic melanoma improved survival in a phase III clinical trial compared with the chemotherapy dacarbazine. The BRAF mutation drives tumor growth in about half of melanoma patients.
Dramatic impact on metastatic melanoma
Researchers reported dramatic reductions in tumor size in a majority of patients and rapid improvement in tumor-related symptoms, such as pain and shortness of breath. However, melanoma tends to resist the new drug within a year in most patients.
Disease progression doesn't necessarily mean it's time to quit this drug, says Kevin Kim, M.D., associate professor in Melanoma, who led MD Anderson's participation in the clinical trials. Melanoma spreads to the brain and to spinal fluid. Kim said treating those metastases separately while continuing vemurafenib has worked well for some patients.
Among those is a young woman who received targeted radiation for brain metastases during the clinical trial while the vemurafenib continued to control the melanoma in her lungs and elsewhere. She has been on the trial since 2008 and is doing well.
"So the conventional wisdom of stopping a therapy if a tumor gets worse anywhere else in the body might not be necessarily true," Kim says, adding that this approach has worked so far in a small number of patients and will need further validation.
The impact of these new drugs on the long-term survival of patients won't be known for some time because they are so new. Near-term effects already can be major.
"An extra year for lung cancer patients with good quality of life --not a year of horrible, intense chemo -- that's huge," Johnson says. "We probably won't cure a whole bunch of patients with this drug, but it's a big step. Understanding the biology of cancer better will lead to a cure."
The NCI Cancer Bulletin has a more detailed report on these FDA approvals.
Nature News reports on development of the antibody-driven drug brentuximab verdotin.
Scientific publications report clinical trial results in the New England Journal of Medicine for crizotinib, brentuximab vedotin and vemurafenib.
MD Anderson Oncolog story about brentuximab vedotin and lymphoma.