Experts say while it can help in advanced disease, that doesn't mean it works at all stages
TUESDAY, Dec. 11, 2012 (HealthDay News) -- Adding the pricey cancer drug Avastin to standard chemotherapy for earlier-stage colon cancer does not extend patients' lives, a new clinical trial finds.
Avastin, known generically as bevacizumab, is approved in the United States to treat advanced-stage colon cancer that has spread to distant sites in the body -- what doctors call metastatic cancer.
Other research has shown that adding Avastin to standard drugs can extend those patients' lives by a few months.
The new trial was set up to see whether the drug could also help patients with earlier-stage cancer, explained lead researcher Dr. Carmen Allegra, chief of hematology and oncology at the University of Florida, in Gainesville.
He and his colleagues found no evidence that the expensive drug -- priced at around $5,000 per month -- kept patients in remission longer or lengthened their lives.
Doctors not involved in the study said it added to evidence that Avastin is of no use to patients with earlier-stage, curable colon cancer.
"I think it's time to move on," said Dr. Jennifer Obel, a medical oncologist with the NorthShore University Health System in suburban Chicago.
The study, reported online Dec. 10 in the Journal of Clinical Oncology, included 2,673 patients who'd had surgery for stage 2 or stage 3 colon cancer -- meaning the tumor was either confined to the colon or had spread no farther than the lymph nodes.
All of the patients were getting "adjuvant," or follow-up, chemotherapy to hopefully take care of any remaining tumor cells and cut the odds of a recurrence.
Allegra's team randomly assigned half of the patients to receive six months of standard chemotherapy -- a three-drug regimen of fluorouracil, leucovorin and oxaliplatin. The other half received that therapy, plus Avastin for one year.
In the end, the addition of Avastin made no difference in survival: About three-quarters of patients in each group were in remission three years later. And five years out, just over 80 percent in each group were still alive.
The findings are similar to those of another trial reported this month, called AVANT, that found Avastin did not help stage 3 colon cancer patients.
"There's no evidence to suggest that this drug should be given in the adjuvant setting," said Dr. Frank Sinicrope, a professor of medicine and oncology at the Mayo Clinic in Rochester, Minn.
Avastin is one of a group of newer, so-called " targeted" cancer drugs -- meaning they interfere with specific proteins that help cancer cells grow and spread. Avastin blocks the formation of blood vessels that feed a tumor's growth and spread. Added to chemotherapy drugs -- which fight tumor cells directly -- Avastin can prolong the lives of people with advanced colon cancer.
No one knows for sure why the drug doesn't benefit people with earlier-stage colon cancer. But Allegra said the same situation has been seen with another " targeted" cancer drug: Erbitux (cetuximab).
He also said the experience with that medication, and now Avastin, raises questions about how drugs for stage 2 and 3 colon cancer are developed.
The current "paradigm," Allegra said, is to first test new drugs in patients with metastatic colon cancer. Only if the drugs show benefit in those trials are they moved to studies of patients with earlier-stage colon cancer.
Mayo's Sinicrope noted that in the past, that's worked.
Often, he said, chemotherapy drugs that have worked for metastatic colon cancer have turned out to work for earlier-stage disease, too. But that has not been the case when it comes to the targeted therapies like Erbitux and Avastin.
"We can't just grab the drug that works in the metastatic setting and cross our fingers that it will work in the adjuvant setting," Sinicrope said.
For patients with colon cancer, he said it's important to remember that if you hear of a new drug that's supposed to be effective for advanced cancer, that doesn't mean it works for everyone.
"Different stages of disease are different biologically, and need to be treated differently," Sinicrope said.
NorthShore's Obel said researchers need a better understanding of the biology of earlier-stage colon cancer, to develop therapies specifically for it. On the other hand, existing therapies are pretty good: "Many of our patients are cured," Obel said.
That's especially true with stage 2 colon cancer, which can often be treated with surgery alone, Obel noted.
She added that the current study is "a very good example of why we need rigorous clinical trials."
"What if doctors just said, 'Well, [Avastin] works for metastatic cancer,' and decided to give it to patients with early-stage disease?" Obel said. "This is an expensive drug that causes side effects, and before you give it, you better know that it's effective."
Learn more about colon cancer treatment from the American Cancer Society (http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-treating-general-info ).
SOURCES: Carmen Allegra, M.D., chief, division of hematology and oncology, University of Florida, Gainesville; Frank Sinicrope, M.D., professor, medicine and oncology, Mayo Clinic, Rochester, Minn.; Jennifer Obel, M.D., medical oncologist, NorthShore University Health System, Illinois; Dec. 10, 2012, Journal of Clinical Oncology