Herceptin® Combined With Chemotherapy Improves Disease–Free Survival for Patients With Early–Stage Breast Cancer
Results from two large randomized clinical trials for patients with HER-2 positive invasive breast cancer show that those patients with early-stage breast cancer who received Herceptin (trastuzumab) in combination with chemotherapy had a significant decrease in risk for breast cancer recurrence compared with patients who received the same chemotherapy without trastuzumab. Patients are considered “HER-2 positive” if their cancer cells "overexpress," or make too much of, a protein called HER–2, which is found on the surface of cancer cells. Trastuzumab slows or stops the growth of these cells, and it is only used to treat cancers that overexpress the HER–2 protein. Approximately 20 percent to 30 percent of breast cancers overexpress HER-2. These tumors tend to grow faster and are generally more likely to recur than tumors that do not overproduce HER-2.
The clinical trials were sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by a network of researchers led by the National Surgical Adjuvant Breast and Bowel Project (NSABP) and the North Central Cancer Treatment Group (NCCTG), in collaboration with the Cancer and Leukemia Group B, the Eastern Cooperative Oncology Group, and the Southwest Oncology Group. Genentech, Inc., South San Francisco, Calif., which manufactures trastuzumab, provided the drug for the trials under the Cooperative Research and Development Agreement (CRADA) with NCI for the clinical development of trastuzumab.
The Data Monitoring Committees overseeing the combined analysis of these trials (known as NSABP-B-31 and NCCTG-N9831)* recommended that the results of a recent combined interim analysis be made public because the studies had met their primary endpoints of increasing disease-free survival (the amount of time patients live without return of the cancer) in patients receiving trastuzumab in combination with chemotherapy. The improvement in overall survival also was statistically significant for women receiving a combination of chemotherapy and trastuzumab.
Patients in the clinical trials who received trastuzumab in combination with standard combination chemotherapy had a 52 percent decrease in disease recurrence compared to patients treated with chemotherapy alone. This difference is highly statistically significant. “This is a major advance for many thousands of women with breast cancer,” said NCI Director Andrew C. von Eschenbach, M.D. “These results are one more example that we are at a major turning point in the use of targeted therapies to eliminate suffering and death from cancer,” he added.
The leaders of the studies underscored the significance of these results and cited the collaborative efforts involved. “These findings confirm that we now have a very potent weapon against the recurrence of cancer cells that overexpress HER-2,” said Edith A. Perez, M.D., who chaired the NCCTG trial and is a medical oncologist at the Mayo Clinic in Jacksonville, Fla. “We gratefully acknowledge the contribution of our co-investigators and, most importantly, our courageous patients in helping to achieve these unprecedented results.”
Edward Romond, M.D., study chair for the NSABP and professor of oncology at the University of Kentucky, in Lexington, Ky., noted, “For women with this type of aggressive breast cancer, the addition of trastuzumab to chemotherapy appears to virtually reverse prognosis from unfavorable to good.”
“These are truly life-saving results in a major disease,” said JoAnne Zujewski, M.D., who oversees breast cancer trials for NCI’s Cancer Therapy Evaluation Program. More detailed results from these studies will be presented at the American Society of Clinical Oncology (ASCO) annual meeting on May 16, 2005, in Orlando, Fla.
Information from over 3,300 patients enrolled in these studies was used for analysis. Patients with operable breast cancer whose tumors over-expressed HER-2 were enrolled in these studies between February 2000 and April 2005. Patients were randomized to receive chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel, or doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab. Most patients had lymph node-positive breast cancer, or breast cancer that had spread to the lymph nodes, with only a minority having lymph node-negative disease. The limited information in the node-negative group did not allow for a separate analysis of this group.
Chemotherapy of the type given in these studies has a risk of congestive heart failure (weakening of the heart muscle) of less than 1 percent. In these studies, the likelihood of congestive heart failure in women receiving the combination of chemotherapy and trastuzumab was increased by 3 percent to 4 percent. Patients in these studies will continue to be followed for any additional side effects. Additional safety data will be presented at ASCO.
Trastuzumab is an example of a “targeted” therapy — an agent that is directed against a specific change in the cancer cell. Trastuzumab was approved for the treatment of advanced breast cancer in 1998.
An estimated 211,240 women will be diagnosed with breast cancer in the United States in 2005. Of these, about 30 percent have lymph node-positive breast cancer, and about 20 percent to 30 percent of these tumors overexpress the HER-2 protein, the target for trastuzumab. Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer-related death in women in this country. An estimated 40,110 deaths from female breast cancer will occur in 2005 in the United States, accounting for about 15 percent of all cancer-related deaths in women in the nation.
Showing posts with label breast cancer drug. Show all posts
Showing posts with label breast cancer drug. Show all posts
Monday, April 28, 2008
Wednesday, July 18, 2007
Taking Cancer Drug With Food May Cut Costs
By Alan MozesHealthDay ReporterTue Jul 17, 7:02 PM ET
TUESDAY, July 17 (HealthDay News) -- Taking a pricey breast cancer drug called lapatinib (Tykerb) with food rather than on an empty stomach may improve its absorption by the body -- lowering the doses needed and greatly cutting costs for patients, a new study shows.
In a commentary published in the Aug. 10 issue of the Journal of Clinical Oncology, Drs. Mark Ratain and Ezra Cohen, of the University of Chicago, suggest that taking the recently approved medication with ood -- particularly high-fat food -- cuts the dosage needed by at least 60 percent.
Ratain -- a professor of medicine and associate director for clinical sciences in UC's Cancer Research Center -- joined Cohen (from the hematology/oncology section of UC's department of medicine) to highlight the findings of a study presented in March at the American Society for Clinical Pharmacology and Therapeutics.
The study, which neither Ratain or Cohen was involved in, revealed that 500 milligrams of Tykerb taken with food appears to be as effective as 1,250 milligrams of the drug taken on an empty stomach, the current prescription protocol.
"What we have here is this unique situation where patients are shelling out more than they need to take a drug in a suboptimal manner," said Ratain.
The current regimen of five 250 milligram tablets per day, taken on an empty stomach, costs about $2,900 per month. But simply taking the pills with food could save the patient about $1,740 per month in drug expenses, a real "value meal" for patients, according to the experts.
Both Ratain and Cohen cautioned that physicians and patients should not alter Tykerb treatment protocols until further research substantiates these findings.
The drug's maker, GlaxoSmithKline (GSK), offered a much stronger warning in a statement released Tuesday, in which they called Ratain's and Cohen's commentary "speculative," with the "potential to be misunderstood and misused by clinicians and patients."
"While dosing Tykerb with food has been found to increase absorption, food effects are highly variable and hard to predict," the company said. "Taking Tykerb with food could result in increased side effects and decreased efficacy. Additionally, concurrent medicines that patients may be taking, including capecitabine, must be considered. Each medicine has its own potential for drug and food interactions. Therefore, it is imperative that patients follow the current FDA approved Tykerb dosing and administration recommendations without food."
Tykerb was approved for use against breast cancer by the U.S. Food and Drug Administration in March of this year. The oral tablet was developed by the GSK for patients battling a specific type of advanced-stage breast cancer, in which HER2 -- a protein that promotes tumor growth -- is expressed.
According to the American Cancer Society, every year approximately 180,000 American women are diagnosed with breast cancer. Annually, upwards of 10,000 women are projected to die from the advanced stage, HER2-positive version of the disease.
The new treatment was approved for use in combination with another medication known as capecitabine (or Xeloda), for cases in which a range of other drugs, such as Herceptin, have ceased to be effective.
According to the FDA, Tykerb inhibits tumor growth by going inside cells containing the HER2 protein and blocking signals that promote tumor growth. In contrast, older drugs such as Herceptin have larger molecular structures that target the outside of the cell.
The FDA approval of Tykerb was based on the results of a study involving approximately 400 breast cancer patients with advanced-stage HER2 disease. That study revealed that women who took Tykerb in combination with capecitabine were significantly more likely to respond positively to treatment and to experience a delay in tumor growth. The ultimate impact Tykerb may have on long-term survival was still unknown at the time of approval.
As is standard procedure with all new drug approvals, the FDA worked with the drug's manufacturer to compose the instruction labeling accompanying Tykerb.
As currently worded, physicians and patients are clearly informed that the medication should be taken on an empty stomach, in light of the fact that all the study patients consuming Tykerb did take the drug without food.
However, another section of the labeling material notes that absorption of the drug is boosted when ingested with food.
Ratain said this kind of confusion happens when "getting things done quickly is considered more important than getting things done right."
"Here's the problem: Since the drug company didn't do their trials with food, they can not recommend that their drug be given with food," he said. "I think if the company knew before they started their trial that food would help absorption, there's no question they would have done the study with food. But they wanted to get the study started quickly, and they guessed wrong."
"So," concludes Ratain, "they had two choices: have the drug approved by the FDA as they had tested it in their trials, or delay the drug until they do new testing with food. And this sort of boxes them into a corner, because the market expectations for this drug is about a billion dollars a year in sales, and they want to get it out there."
"So, the bottom line is that, in the end, the label in one part says take it fasting, and in another place, it says the concentration and absorption in the blood is markedly increased if taken with food," Ratain noted. "The remedy is potentially to take a lower dose with food, which results in a significantly lower cost to the patient and/or their payers."
Ratain emphasized that Tykerb's interaction with food must now undergo further study before it can definitively be said that the current labeling instructions should be altered. However, he pointed out that he is not aware of any current plans on the part of GSK or a third party to conduct such a study.
Meanwhile, Ratain said that he and his colleague Cohen simply want to draw attention to a clear labeling discrepancy with major financial implications for breast cancer patients -- one that he believes might very well have slipped through the cracks in the complex world of oncology treatment.
Dr. David Flockhart is director of the division of clinical pharmacology at Indiana University School of Medicine in Indianapolis. He said he's inclined to agree that Ratain and Cohen have identified a hidden cost saving for patients.
"I think Ratain's probably right," said Flockhart. "Drugs are usually studied for concentration effects on fasting volunteers. This is routine, because it's very hard to predict how food may speed up or bind with a drug and alter absorption. So, the drug company did what they would normally do. But there happens to be a nice little accident here that could benefit patients."
"Of course, they're calling for more studies," he noted. "As is needed. Meanwhile, because tons of labels don't have perfect instructions in them, doctors will try to do what they always do: use the best information they have. And doctors may want to consider this new information," Flockhart said.
By Alan MozesHealthDay ReporterTue Jul 17, 7:02 PM ET
TUESDAY, July 17 (HealthDay News) -- Taking a pricey breast cancer drug called lapatinib (Tykerb) with food rather than on an empty stomach may improve its absorption by the body -- lowering the doses needed and greatly cutting costs for patients, a new study shows.
In a commentary published in the Aug. 10 issue of the Journal of Clinical Oncology, Drs. Mark Ratain and Ezra Cohen, of the University of Chicago, suggest that taking the recently approved medication with ood -- particularly high-fat food -- cuts the dosage needed by at least 60 percent.
Ratain -- a professor of medicine and associate director for clinical sciences in UC's Cancer Research Center -- joined Cohen (from the hematology/oncology section of UC's department of medicine) to highlight the findings of a study presented in March at the American Society for Clinical Pharmacology and Therapeutics.
The study, which neither Ratain or Cohen was involved in, revealed that 500 milligrams of Tykerb taken with food appears to be as effective as 1,250 milligrams of the drug taken on an empty stomach, the current prescription protocol.
"What we have here is this unique situation where patients are shelling out more than they need to take a drug in a suboptimal manner," said Ratain.
The current regimen of five 250 milligram tablets per day, taken on an empty stomach, costs about $2,900 per month. But simply taking the pills with food could save the patient about $1,740 per month in drug expenses, a real "value meal" for patients, according to the experts.
Both Ratain and Cohen cautioned that physicians and patients should not alter Tykerb treatment protocols until further research substantiates these findings.
The drug's maker, GlaxoSmithKline (GSK), offered a much stronger warning in a statement released Tuesday, in which they called Ratain's and Cohen's commentary "speculative," with the "potential to be misunderstood and misused by clinicians and patients."
"While dosing Tykerb with food has been found to increase absorption, food effects are highly variable and hard to predict," the company said. "Taking Tykerb with food could result in increased side effects and decreased efficacy. Additionally, concurrent medicines that patients may be taking, including capecitabine, must be considered. Each medicine has its own potential for drug and food interactions. Therefore, it is imperative that patients follow the current FDA approved Tykerb dosing and administration recommendations without food."
Tykerb was approved for use against breast cancer by the U.S. Food and Drug Administration in March of this year. The oral tablet was developed by the GSK for patients battling a specific type of advanced-stage breast cancer, in which HER2 -- a protein that promotes tumor growth -- is expressed.
According to the American Cancer Society, every year approximately 180,000 American women are diagnosed with breast cancer. Annually, upwards of 10,000 women are projected to die from the advanced stage, HER2-positive version of the disease.
The new treatment was approved for use in combination with another medication known as capecitabine (or Xeloda), for cases in which a range of other drugs, such as Herceptin, have ceased to be effective.
According to the FDA, Tykerb inhibits tumor growth by going inside cells containing the HER2 protein and blocking signals that promote tumor growth. In contrast, older drugs such as Herceptin have larger molecular structures that target the outside of the cell.
The FDA approval of Tykerb was based on the results of a study involving approximately 400 breast cancer patients with advanced-stage HER2 disease. That study revealed that women who took Tykerb in combination with capecitabine were significantly more likely to respond positively to treatment and to experience a delay in tumor growth. The ultimate impact Tykerb may have on long-term survival was still unknown at the time of approval.
As is standard procedure with all new drug approvals, the FDA worked with the drug's manufacturer to compose the instruction labeling accompanying Tykerb.
As currently worded, physicians and patients are clearly informed that the medication should be taken on an empty stomach, in light of the fact that all the study patients consuming Tykerb did take the drug without food.
However, another section of the labeling material notes that absorption of the drug is boosted when ingested with food.
Ratain said this kind of confusion happens when "getting things done quickly is considered more important than getting things done right."
"Here's the problem: Since the drug company didn't do their trials with food, they can not recommend that their drug be given with food," he said. "I think if the company knew before they started their trial that food would help absorption, there's no question they would have done the study with food. But they wanted to get the study started quickly, and they guessed wrong."
"So," concludes Ratain, "they had two choices: have the drug approved by the FDA as they had tested it in their trials, or delay the drug until they do new testing with food. And this sort of boxes them into a corner, because the market expectations for this drug is about a billion dollars a year in sales, and they want to get it out there."
"So, the bottom line is that, in the end, the label in one part says take it fasting, and in another place, it says the concentration and absorption in the blood is markedly increased if taken with food," Ratain noted. "The remedy is potentially to take a lower dose with food, which results in a significantly lower cost to the patient and/or their payers."
Ratain emphasized that Tykerb's interaction with food must now undergo further study before it can definitively be said that the current labeling instructions should be altered. However, he pointed out that he is not aware of any current plans on the part of GSK or a third party to conduct such a study.
Meanwhile, Ratain said that he and his colleague Cohen simply want to draw attention to a clear labeling discrepancy with major financial implications for breast cancer patients -- one that he believes might very well have slipped through the cracks in the complex world of oncology treatment.
Dr. David Flockhart is director of the division of clinical pharmacology at Indiana University School of Medicine in Indianapolis. He said he's inclined to agree that Ratain and Cohen have identified a hidden cost saving for patients.
"I think Ratain's probably right," said Flockhart. "Drugs are usually studied for concentration effects on fasting volunteers. This is routine, because it's very hard to predict how food may speed up or bind with a drug and alter absorption. So, the drug company did what they would normally do. But there happens to be a nice little accident here that could benefit patients."
"Of course, they're calling for more studies," he noted. "As is needed. Meanwhile, because tons of labels don't have perfect instructions in them, doctors will try to do what they always do: use the best information they have. And doctors may want to consider this new information," Flockhart said.
Tuesday, March 13, 2007
FDA approves advanced breast cancer drug
Women with an aggressive form of advanced breast cancer that other treatments have failed to stop gained a new option Tuesday with the approval of a novel drug — but how much benefit it offers is unclear.
The GlaxoSmithKline PLC drug, Tykerb, is to be taken once daily in pill form and is meant for women who have received prior treatment with the intravenous drug Herceptin and older chemotherapy drugs called taxanes and anthracyclines, the company said. The Food and Drug Administration said it approved Tykerb for use in conjunction with the chemotherapy drug Xeloda.
Glaxo said Tykerb would be available in two weeks. It will cost about $2,900 a month, the company said.
http://news.yahoo.com/s/ap/20070313/ap_on_he_me/breast_cancer
The GlaxoSmithKline PLC drug, Tykerb, is to be taken once daily in pill form and is meant for women who have received prior treatment with the intravenous drug Herceptin and older chemotherapy drugs called taxanes and anthracyclines, the company said. The Food and Drug Administration said it approved Tykerb for use in conjunction with the chemotherapy drug Xeloda.
Glaxo said Tykerb would be available in two weeks. It will cost about $2,900 a month, the company said.
http://news.yahoo.com/s/ap/20070313/ap_on_he_me/breast_cancer
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