Merck KGaA’s Erbitux Failed to Extend Lives in Study (Update3)
By Naomi Kresge
Sept. 23 (Bloomberg) -- Merck KGaA and Eli Lilly & Co.’s Erbitux drug failed to lengthen colon cancer patients’ lives or keep their disease from worsening, researchers said in an independent study that may limit use of the medicine.
Erbitux surprised researchers by not keeping cancer at bay in its target group of patients, people with a normal version of the so-called KRAS gene, lead author Timothy Maughan, a professor of cancer studies at the School of Medicine at Cardiff University, said in an interview. Based on previous studies, researchers expected those people to benefit, while a mutant version of the gene would foil the drug.
The results of the so-called COIN trial, released today at the European Cancer Organization and European Society for Medical Oncology conference in Berlin, contradict data that Merck presented separately today. The German drugmaker’s own study found that Erbitux helped normal KRAS patients live an average 3.5 months longer than those given chemotherapy alone.
“We really, really expected progression-free survival to be better,” Maughan said, referring to the length of time before patients’ tumors get worse. “It’s absolutely shocking.”
The benefit of Erbitux in both trials was disappointing, said Scott Kopetz, assistant professor of gastrointestinal medical oncology at M.D. Anderson Cancer Center in Houston. The results probably will influence care, limiting Erbitux use mainly to patients who undergo therapy in the hope that their tumors will shrink and subsequent surgery can be done, he said.
‘Standard of Care’
Roche Holding AG’s Avastin “remains the default standard of care, in combination with chemotherapy,” he said in a telephone interview. “We need to see better results than these in order to change that.”
The discrepancy between the studies may be the result of differences in the types of chemotherapy patients received alongside Erbitux, known chemically as cetuximab, Maughan said. About two-thirds of the patients in the U.K. trial chose Roche’s Xeloda, known generically as capecitabine, a chemotherapy pill. The Merck study, known as Crystal, combined Erbitux with standard infused chemotherapy.
Merck shares fell 1.77 euros, or 2.6 percent, to close at 67 euros in Frankfurt trading. The stock rose as much as 2.9 percent earlier today, when the results of the Crystal study were released.
Patients in the U.K. study who received Erbitux also got less chemotherapy and other medicine, based on an analysis of 800 of the people in the trial, Maughan said. This is because their side effects were so much worse -- 70 percent of the Erbitux group had serious side effects, compared with half of the others -- that their doctors cut their chemotherapy dosages.
Patient Enrollment
The U.K. trial didn’t put any restrictions on colon cancer patients allowed to join, meaning that the people who enrolled were sicker than is common in pharmaceutical company trials. Forty percent hadn’t had their main tumors surgically removed, and five percent of the patients had cancer that had spread again immediately after previous surgery and treatment.
The only patients to be helped were a small group with a normal KRAS gene whose inoperable cancer had spread only to the liver. Erbitux reduced the risk of dying by about 23 percent for that group, though the group was too small for the result to be statistically significant, Maughan said. These are the only colon cancer patients approved to get Erbitux under the National Institute for Health and Clinical Excellence, the U.K. adviser on medical spending.
Skepticism
The results could leave doctors skeptical about using Erbitux as a first-line treatment in combination with Xeloda, Maughan said. Researchers are still analyzing the data.
“It clearly doesn’t mean that cetuximab doesn’t work,” he said. “I don’t think we’ve gotten to the whole bottom line of the story.”
The contradictory Merck trial released today is the first time anyone has shown Erbitux helps patients live longer, lead author Eric Van Cutsem, a professor at University Hospital Gasthuisberg in Belgium, said before the results were released. The trial tested tumors from patients in a previous Erbitux trial to find enough people with normal KRAS genes for researchers to draw conclusions.
“These are the first survival data ever,” Wolfgang Wein, executive vice president of oncology at Merck, said in an interview this week. “They are robust. They are highly significant.”
The independent study, on the other hand, drew from a “very frail and maybe not so typical population,” Wein said.
U.K. Study
Had the U.K. study shown that Erbitux keeps colon cancer patients alive, the therapy could have challenged sales of Swiss drugmaker Roche’s Avastin in Europe, said Amit Roy, head of health-care equity research at Nomura International in London, in a note to clients before the results were released. No other drug has been shown to keep patients alive in combination with modern chemotherapy, he said.
Lilly and partner Bristol-Myers Squibb Co. market Erbitux in the U.S., while Merck sells it elsewhere. Sales of the drug outside the U.S. are not likely to reach 1 billion euros ($1.48 billion) a year before 2011, Wein said. The European Union in July rejected the drug as a treatment for a form of lung cancer. It’s approved for use in colorectal as well as head and neck tumors.
Merck, which is based in Darmstadt and not affiliated with U.S. drugmaker Merck & Co., provided Erbitux for the U.K. trial, sponsored by the London-based Medical Research Council.
Now doctors will have the task of weighing the differences between Merck’s results and the independent trial, said Richard Adams, an investigator on the U.K. trial and a senior lecturer in oncology at Cardiff University.
“I suspect clinicians may increase their use of cetuximab in a first-line setting, but then they’ve got to weigh that against Avastin as well,” Adams said. “It’s a very complex area all of a sudden.”
To contact the reporter on this story: Naomi Kresge in Berlin at nkresge@bloomberg.net
Last Updated: September 23, 2009 11:45 EDT
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