January 25, 2012 — The addition of oxaliplatin to adjuvant 5-fluorouracil in patients with stage III colon cancer is just as effective at improving survival in real-world community settings as it is in randomized clinical trials (RCTs), according to the results of a study published online January 20 in the Journal of the National Cancer Institute.
"This is confirmation that the drug is really of benefit," Hanna K. Sanoff, MD, from the University of Virginia, Charlottesville, and the study's lead author, told Medscape Medical News.
"It's good news," she continued. "Even if things aren't done perfectly, like they are in clinical trials, we seem to still be helping patients in the real world get cured of their colon cancer. That's the good message to take from this study."
The effectiveness of oxaliplatin has been proven in RCTs, but the patients in such trials are younger, healthier, and less racially diverse than in the general cancer population. Overall, less than 2% of patients with stage III colon cancer are enrolled in RCTs.
To assess outcomes in the general population, Dr. Sanoff and her colleagues gathered data from 5 observational data sources: the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER–Medicare); the New York State Cancer Registry (NYSCR) linked to Medicaid claims; the NYSCR linked to Medicare claims; the National Comprehensive Cancer Network (NCCN) Outcomes Database; and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS).
All patients had stage III colon cancer, received chemotherapy within 120 days of surgery, and were 75 years or younger.
"There are a few different ways to look at real-world outcomes, and one is not necessarily better than another. In fact, there's no good way in the United States to do a global, whole-country assessment. One of the reasons we did it like this, with all these different groups, was to try to get a better sense of how these diverse groups might have differed," she said.
"If you look at Medicaid patients, who are probably different than Medicare patients, and patients treated at great cancer centers, which is what the NCCN is, and you look at people in CanCORS, which has VA patients and a couple of HMOs, [it makes] a pretty diverse group. We wanted to try to get as broad a look as we could," Dr. Sanoff explained.
Next, the researchers compared overall survival between patients treated with oxaliplatin and those treated with nonoxaliplatin adjuvant chemotherapy in the community databases and in 5 RCTs in the Adjuvant Colon Cancer Endpoints (ACCENT) group.
"We used the data from 5 different trials — X-ACT, PETACC-3, MOSAIC, C-07, and C89803 — and used that as our gold standard," Dr. Sanoff explained.
The 3-year overall survival among the 1273 patients in the pooled RCTs was 86%. There was a 4% absolute and a 20% relative improvement in survival, compared with nonoxaliplatin-treated patients (adjusted hazard ratio of death, 0.80; 95% confidence interval, 0.70 to 0.92; P = .002).
Survival was "remarkably" similar in community-treated patients.
In the patients in the SEER–Medicare group (n = 1152), 3-year overall survival was 80%; in the CanCORS group (n = 129), it was 88%; in the NYSCR–Medicaid group (n = 54), it was 82%; in the NYSCR–Medicare group (n = 180), it was 79%; and in the NCCN group (n = 438), it was 86%.
The survival advantage was maintained in older, sicker, and minority patients.
Study Allays Concerns
Commenting on this study for Medscape Medical News, Alok A. Khorana, MBBS, from the University of Rochester School of Medicine and Dentistry in New York, affirmed the study's conclusion.
"Oxaliplatin-based combination therapy is generally accepted to be the standard of care for adjuvant treatment in the stage III setting, based on large multiple RCTs; however concerns have been raised that the real-world population differs substantially from patients enrolled in clinical trials. In particular, patients with comorbidities, older patients, and minorities are often underrepresented," he said.
This study of real-world outcomes demonstrates that oxaliplatin is associated with better outcomes in the community setting, "and thus does much to allay these concerns," he said.
Dr. Khorana pointed out that although this was an outcomes study, the patients were not randomly assigned to oxaliplatin; therefore, the study does not have the same level of evidence as an RCT. "But it is indeed consistent with the data from RCTs," he said.
Dr. Sanoff has disclosed no relevant financial relationships. Dr. Khorana reports receiving honoraria/consulting fees from sanofi-aventis, the maker of oxaliplatin.
J Natl Cancer Inst. Published online January 20, 2012. Abstract
"This is confirmation that the drug is really of benefit," Hanna K. Sanoff, MD, from the University of Virginia, Charlottesville, and the study's lead author, told Medscape Medical News.
"It's good news," she continued. "Even if things aren't done perfectly, like they are in clinical trials, we seem to still be helping patients in the real world get cured of their colon cancer. That's the good message to take from this study."
The effectiveness of oxaliplatin has been proven in RCTs, but the patients in such trials are younger, healthier, and less racially diverse than in the general cancer population. Overall, less than 2% of patients with stage III colon cancer are enrolled in RCTs.
To assess outcomes in the general population, Dr. Sanoff and her colleagues gathered data from 5 observational data sources: the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER–Medicare); the New York State Cancer Registry (NYSCR) linked to Medicaid claims; the NYSCR linked to Medicare claims; the National Comprehensive Cancer Network (NCCN) Outcomes Database; and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS).
All patients had stage III colon cancer, received chemotherapy within 120 days of surgery, and were 75 years or younger.
"There are a few different ways to look at real-world outcomes, and one is not necessarily better than another. In fact, there's no good way in the United States to do a global, whole-country assessment. One of the reasons we did it like this, with all these different groups, was to try to get a better sense of how these diverse groups might have differed," she said.
"If you look at Medicaid patients, who are probably different than Medicare patients, and patients treated at great cancer centers, which is what the NCCN is, and you look at people in CanCORS, which has VA patients and a couple of HMOs, [it makes] a pretty diverse group. We wanted to try to get as broad a look as we could," Dr. Sanoff explained.
Next, the researchers compared overall survival between patients treated with oxaliplatin and those treated with nonoxaliplatin adjuvant chemotherapy in the community databases and in 5 RCTs in the Adjuvant Colon Cancer Endpoints (ACCENT) group.
"We used the data from 5 different trials — X-ACT, PETACC-3, MOSAIC, C-07, and C89803 — and used that as our gold standard," Dr. Sanoff explained.
The 3-year overall survival among the 1273 patients in the pooled RCTs was 86%. There was a 4% absolute and a 20% relative improvement in survival, compared with nonoxaliplatin-treated patients (adjusted hazard ratio of death, 0.80; 95% confidence interval, 0.70 to 0.92; P = .002).
Survival was "remarkably" similar in community-treated patients.
In the patients in the SEER–Medicare group (n = 1152), 3-year overall survival was 80%; in the CanCORS group (n = 129), it was 88%; in the NYSCR–Medicaid group (n = 54), it was 82%; in the NYSCR–Medicare group (n = 180), it was 79%; and in the NCCN group (n = 438), it was 86%.
The survival advantage was maintained in older, sicker, and minority patients.
Study Allays Concerns
Commenting on this study for Medscape Medical News, Alok A. Khorana, MBBS, from the University of Rochester School of Medicine and Dentistry in New York, affirmed the study's conclusion.
"Oxaliplatin-based combination therapy is generally accepted to be the standard of care for adjuvant treatment in the stage III setting, based on large multiple RCTs; however concerns have been raised that the real-world population differs substantially from patients enrolled in clinical trials. In particular, patients with comorbidities, older patients, and minorities are often underrepresented," he said.
This study of real-world outcomes demonstrates that oxaliplatin is associated with better outcomes in the community setting, "and thus does much to allay these concerns," he said.
Dr. Khorana pointed out that although this was an outcomes study, the patients were not randomly assigned to oxaliplatin; therefore, the study does not have the same level of evidence as an RCT. "But it is indeed consistent with the data from RCTs," he said.
Dr. Sanoff has disclosed no relevant financial relationships. Dr. Khorana reports receiving honoraria/consulting fees from sanofi-aventis, the maker of oxaliplatin.
J Natl Cancer Inst. Published online January 20, 2012. Abstract
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