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FOLFOXIRI bests FOLFIRI when bevacizumab is added in colorectal cancer
SAN FRANCISCO – Adding bevacizumab to the FOLFOXIRI regimen significantly delayed the median time to progression of metastatic colorectal cancer to 12.2 months, compared with 9.7 months when bevacizumab was added to the FOLFIRI regimen, a phase III trial of 508 patients found.
Previous data had shown inferior progression-free survival, treatment response, and overall survival rates when treating metastatic colorectal cancer with FOLFIRI – which combines folinic acid (leucovorin), fluorouracil, and irinotecan – compared with FOLFOXIRI, which adds oxaliplatin to the drugs used in FOLFIRI.
The current study confirms the superiority of first-line FOLFOXIRI over FOLFIRI and shows that FOLFOXIRI remains the better regimen when adding bevacizumab (Avastin) for select patients, Dr. Fotios Loupakis said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.
At 2 years of follow-up, 20% of patients in the FOLFOXIRI/bevacizumab group and 11% in the FOLFIRI/bevacizumab group were free of disease progression, a significant difference, reported Dr. Loupakis of the University of Pisa (Italy) and his associates.
"Based on these results, FOLFOXIRI plus bevacizumab represents a new option for the treatment of metastatic colorectal cancer patients selected according to the eligibility criteria of this study," he said.
The multicenter study, known as the TRIBE trial, randomized adults in Italy aged 18-75 years who had unresectable metastatic colon cancer with histologically proven adenocarcinoma; at least one measurable lesion; and adequate bone marrow, liver, and renal functions. Patients younger than 71 years had to have an Eastern Cooperative Oncology Group performance status score of 0, and patients aged 71-75 years had a performance status score no higher than 2. Previous adjuvant chemotherapy containing oxaliplatin was allowed if more than 12 months had passed between the end of adjuvant therapy and the first relapse.
Subgroup analyses found better progression-free survival with FOLFOXIRI/bevacizumab in all subgroups.
Among secondary outcomes, the treatment response rate was significantly higher in the FOLFOXIRI/bevacizumab group (65%), compared with the FOLFIRI/bevacizumab group (53%), an intent-to-treat analysis showed.
Safety data on 504 patients revealed "moderately" increased rates of grade 3 or 4 diarrhea (19%), stomatitis (9%), and neutropenia (50%) in the FOLFOXIRI/bevacizumab group, compared with rates in the FOLFIRI/bevacizumab group (11% had diarrhea, 4% had stomatitis, and 20% had neutropenia), he said. The differences between groups in adverse events were statistically significant.
The two groups did not differ significantly, however, in the rate of grade 3 or 4 febrile neutropenia, the overall rate of serious adverse events, or the rate of treatment-related death. Nine percent of patients in the FOLFOXIRI/bevacizumab group developed grade 3 or 4 febrile neutropenia, compared with 6% of patients in the FOLFIRI/bevacizumab group. Serious adverse events were seen in 20% of each group, and approximately 2% in each group died of causes related to treatment.
Dr. Loupakis called the overall safety profile of FOLFOXIRI plus bevacizumab "acceptable." The study did not collect data on patients’ quality of life, he said.
Baseline demographics and disease characteristics were similar between groups.
The investigators are in the process of analyzing data on overall survival, secondary resections, treatment after disease progression, and potential biomarkers of response to treatment.
A previous phase II clinical trial of FOLFOXIRI plus bevacizumab had suggested promising results in terms of progression-free survival with acceptable toxicity, he said.
Dr. Loupakis has been a consultant for Bayer. Roche, which markets bevacizumab, provided support for the study. One of his associates in the study reported financial relationships with Roche, Amgen, Merck, and Sanofi.
On Twitter @SherryBoschert
SAN FRANCISCO – Adding bevacizumab to the FOLFOXIRI regimen significantly delayed the median time to progression of metastatic colorectal cancer to 12.2 months, compared with 9.7 months when bevacizumab was added to the FOLFIRI regimen, a phase III trial of 508 patients found.
Previous data had shown inferior progression-free survival, treatment response, and overall survival rates when treating metastatic colorectal cancer with FOLFIRI – which combines folinic acid (leucovorin), fluorouracil, and irinotecan – compared with FOLFOXIRI, which adds oxaliplatin to the drugs used in FOLFIRI.
The current study confirms the superiority of first-line FOLFOXIRI over FOLFIRI and shows that FOLFOXIRI remains the better regimen when adding bevacizumab (Avastin) for select patients, Dr. Fotios Loupakis said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.
At 2 years of follow-up, 20% of patients in the FOLFOXIRI/bevacizumab group and 11% in the FOLFIRI/bevacizumab group were free of disease progression, a significant difference, reported Dr. Loupakis of the University of Pisa (Italy) and his associates.
"Based on these results, FOLFOXIRI plus bevacizumab represents a new option for the treatment of metastatic colorectal cancer patients selected according to the eligibility criteria of this study," he said.
The multicenter study, known as the TRIBE trial, randomized adults in Italy aged 18-75 years who had unresectable metastatic colon cancer with histologically proven adenocarcinoma; at least one measurable lesion; and adequate bone marrow, liver, and renal functions. Patients younger than 71 years had to have an Eastern Cooperative Oncology Group performance status score of 0, and patients aged 71-75 years had a performance status score no higher than 2. Previous adjuvant chemotherapy containing oxaliplatin was allowed if more than 12 months had passed between the end of adjuvant therapy and the first relapse.
Subgroup analyses found better progression-free survival with FOLFOXIRI/bevacizumab in all subgroups.
Among secondary outcomes, the treatment response rate was significantly higher in the FOLFOXIRI/bevacizumab group (65%), compared with the FOLFIRI/bevacizumab group (53%), an intent-to-treat analysis showed.
Safety data on 504 patients revealed "moderately" increased rates of grade 3 or 4 diarrhea (19%), stomatitis (9%), and neutropenia (50%) in the FOLFOXIRI/bevacizumab group, compared with rates in the FOLFIRI/bevacizumab group (11% had diarrhea, 4% had stomatitis, and 20% had neutropenia), he said. The differences between groups in adverse events were statistically significant.
The two groups did not differ significantly, however, in the rate of grade 3 or 4 febrile neutropenia, the overall rate of serious adverse events, or the rate of treatment-related death. Nine percent of patients in the FOLFOXIRI/bevacizumab group developed grade 3 or 4 febrile neutropenia, compared with 6% of patients in the FOLFIRI/bevacizumab group. Serious adverse events were seen in 20% of each group, and approximately 2% in each group died of causes related to treatment.
Dr. Loupakis called the overall safety profile of FOLFOXIRI plus bevacizumab "acceptable." The study did not collect data on patients’ quality of life, he said.
Baseline demographics and disease characteristics were similar between groups.
The investigators are in the process of analyzing data on overall survival, secondary resections, treatment after disease progression, and potential biomarkers of response to treatment.
A previous phase II clinical trial of FOLFOXIRI plus bevacizumab had suggested promising results in terms of progression-free survival with acceptable toxicity, he said.
Dr. Loupakis has been a consultant for Bayer. Roche, which markets bevacizumab, provided support for the study. One of his associates in the study reported financial relationships with Roche, Amgen, Merck, and Sanofi.
On Twitter @SherryBoschert
SAN FRANCISCO – Adding bevacizumab to the FOLFOXIRI regimen significantly delayed the median time to progression of metastatic colorectal cancer to 12.2 months, compared with 9.7 months when bevacizumab was added to the FOLFIRI regimen, a phase III trial of 508 patients found.
Previous data had shown inferior progression-free survival, treatment response, and overall survival rates when treating metastatic colorectal cancer with FOLFIRI – which combines folinic acid (leucovorin), fluorouracil, and irinotecan – compared with FOLFOXIRI, which adds oxaliplatin to the drugs used in FOLFIRI.
The current study confirms the superiority of first-line FOLFOXIRI over FOLFIRI and shows that FOLFOXIRI remains the better regimen when adding bevacizumab (Avastin) for select patients, Dr. Fotios Loupakis said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.
At 2 years of follow-up, 20% of patients in the FOLFOXIRI/bevacizumab group and 11% in the FOLFIRI/bevacizumab group were free of disease progression, a significant difference, reported Dr. Loupakis of the University of Pisa (Italy) and his associates.
"Based on these results, FOLFOXIRI plus bevacizumab represents a new option for the treatment of metastatic colorectal cancer patients selected according to the eligibility criteria of this study," he said.
The multicenter study, known as the TRIBE trial, randomized adults in Italy aged 18-75 years who had unresectable metastatic colon cancer with histologically proven adenocarcinoma; at least one measurable lesion; and adequate bone marrow, liver, and renal functions. Patients younger than 71 years had to have an Eastern Cooperative Oncology Group performance status score of 0, and patients aged 71-75 years had a performance status score no higher than 2. Previous adjuvant chemotherapy containing oxaliplatin was allowed if more than 12 months had passed between the end of adjuvant therapy and the first relapse.
Subgroup analyses found better progression-free survival with FOLFOXIRI/bevacizumab in all subgroups.
Among secondary outcomes, the treatment response rate was significantly higher in the FOLFOXIRI/bevacizumab group (65%), compared with the FOLFIRI/bevacizumab group (53%), an intent-to-treat analysis showed.
Safety data on 504 patients revealed "moderately" increased rates of grade 3 or 4 diarrhea (19%), stomatitis (9%), and neutropenia (50%) in the FOLFOXIRI/bevacizumab group, compared with rates in the FOLFIRI/bevacizumab group (11% had diarrhea, 4% had stomatitis, and 20% had neutropenia), he said. The differences between groups in adverse events were statistically significant.
The two groups did not differ significantly, however, in the rate of grade 3 or 4 febrile neutropenia, the overall rate of serious adverse events, or the rate of treatment-related death. Nine percent of patients in the FOLFOXIRI/bevacizumab group developed grade 3 or 4 febrile neutropenia, compared with 6% of patients in the FOLFIRI/bevacizumab group. Serious adverse events were seen in 20% of each group, and approximately 2% in each group died of causes related to treatment.
Dr. Loupakis called the overall safety profile of FOLFOXIRI plus bevacizumab "acceptable." The study did not collect data on patients’ quality of life, he said.
Baseline demographics and disease characteristics were similar between groups.
The investigators are in the process of analyzing data on overall survival, secondary resections, treatment after disease progression, and potential biomarkers of response to treatment.
A previous phase II clinical trial of FOLFOXIRI plus bevacizumab had suggested promising results in terms of progression-free survival with acceptable toxicity, he said.
Dr. Loupakis has been a consultant for Bayer. Roche, which markets bevacizumab, provided support for the study. One of his associates in the study reported financial relationships with Roche, Amgen, Merck, and Sanofi.
On Twitter @SherryBoschert
AT THE ASCO GASTROINTESTINAL CANCERS SYMPOSIUM
Major Finding: The time to progression of metastatic colorectal cancer was significantly longer after first-line treatment with FOLFOXIRI plus bevacizumab (12.2 months), compared with FOLFIRI plus bevacizumab (9.7 months).
Data Source: Multicenter, randomized, phase III Italian trial of 508 patients with unresectable metastatic colorectal cancer.
Disclosures: Dr. Loupakis has been a consultant for Bayer. Roche, which markets bevacizumab, provided support for the study.
Selective resection feasible for esophageal cancer
SAN FRANCISCO – Five-year survival rates for 41 patients with locoregionally advanced esophageal cancer who underwent induction chemotherapy and definitive chemoradiotherapy were 53% for patients with a clinical complete response who avoided surgery, 33% for patients with suspected residual disease, and 41% for patients with suspected residual disease who were able to undergo surgery.
The multicenter phase II Radiation Therapy Oncology Group (RTOG) 0246 trial suggests that the organ-preserving strategy of selective esophageal resection after definitive chemoradiation can be an effective approach, Dr. Stephen Swisher said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology (ASCO).
Forty-one of the 43 patients enrolled with nonmetastatic resectable esophageal cancer had enough data to be included in the final analysis. Thirty-seven patients completed both induction chemotherapy and definitive chemoradiotherapy. Four patients died from problems associated with treatment (10%), two related to induction chemotherapy, one related to chemoradiation, and one related to surgery.
The overall 5-year survival rate after a median follow-up of 6.7 years was 37% in an intention-to-treat analysis, which is similar to results of trials of other treatment modalities for locoregionally advanced esophageal cancer, he said. Patients with a clinical complete response to chemoradiotherapy had a median survival of 66 months, compared with 15 months for all patients with suspected residual disease and 36 months for patients with suspected residual disease who were able to undergo surgery, reported Dr. Swisher of the University of Texas M.D. Anderson Cancer Center, Houston, and his associates.
During enrollment in 2003-2006, 15 patients came from the M.D. Anderson Cancer Center; 18 other sites contributed 1-3 patients each. Twenty-nine patients had adenocarcinomas (73%). Pretreatment clinical stages were T3 or greater in 31 patients (76%) and N1 in 29 patients (71%).
All underwent two cycles of induction chemotherapy with 5-fluorouracil (5-FU), cisplatin, and paclitaxel, followed by concurrent chemoradiation and daily 5-FU with cisplatin over the first 5 days.
After definitive chemoradiation, patients underwent chest and abdominal imaging to look for residual locoregional disease using CT scans, esophageal ultrasound, and optional PET scans. Those with no suspected residual disease were observed and monitored for recurrence every 3 months for the first 6 months, then every 6 months for the next 18 months, and then yearly. Patients with suspected residual disease were considered for immediate surgery.
Ultimately, 21 patients (51% of the total) underwent surgery: 17 had selective esophagectomies due to suspected residual cancer; 1 patient with a clinical complete response after chemoradiotherapy requested surgery; and 3 patients who were thought to have clinical complete responses underwent salvage esophagectomies due to recurrent cancer 5-15 months after chemoradiotherapy.
Besides the 17 patients with suspected residual cancer who underwent surgery, 4 others with a noncomplete response to chemoradiotherapy did not have esophagectomies because of metastatic disease in 3 patients and inoperable local disease in 1 patient.
The investigators previously reported preliminary results showing an overall 1-year survival rate of 71% in the study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Swisher reported having no financial disclosures.
On Twitter @sherryboschert
This study provides a start toward "what we should be doing in cancer service delivery," which is creating a customized or tailored approach to delivery of services, Dr. Donald Low said. Eliminating esophagectomy when feasible is "probably appropriate, considering the historical perspective of bad outcomes in esophageal resection."
 |
Courtesy of the American Society of Clinical Oncology
|
The RTOG 0246 trial addresses an important clinical issue and looks at a new approach of neoadjuvant therapy and selective surgery. One of the study’s strengths is that surveillance was very scheduled and orchestrated – there was a branch point at which the decision was made to have or not have surgery. How that surveillance would fit into real-world practice is unclear and important to consider, he said. The long-term follow-up is another strength of the study.
On the other hand, it has several weaknesses. A large number of participating centers yielded a relatively limited number of study participants: 79% of the centers contributed fewer than two patients, and only the M.D. Anderson center contributed more than three patients. The cancers were mostly adenocarcinomas, but the study included some squamous cell cancers and esophageal or esophagogastric junction tumors – a mixed presentation that makes analysis of results more complex. There were no stage-by-stage comparisons of results, and the study included everything from T2 N0 to T3 N1 stage disease.
In addition, there was no reliable current methodology for accurately identifying complete pathological response without surgical resection. "Remember, that’s the important issue, because at some point you have to sit down with a physiologically intact person and give an impression as to whether they’ve had a complete response," he said.
Dr. Donald Low is head of the section on general thoracic surgery and thoracic oncology at Virginia Mason Medical Center, Seattle. This is a portion of his discussion of Dr. Swisher’s study at the meeting. Dr. Low has received honoraria from Boston Scientific.
This study provides a start toward "what we should be doing in cancer service delivery," which is creating a customized or tailored approach to delivery of services, Dr. Donald Low said. Eliminating esophagectomy when feasible is "probably appropriate, considering the historical perspective of bad outcomes in esophageal resection."
|
Courtesy of the American Society of Clinical Oncology
|
The RTOG 0246 trial addresses an important clinical issue and looks at a new approach of neoadjuvant therapy and selective surgery. One of the study’s strengths is that surveillance was very scheduled and orchestrated – there was a branch point at which the decision was made to have or not have surgery. How that surveillance would fit into real-world practice is unclear and important to consider, he said. The long-term follow-up is another strength of the study.
On the other hand, it has several weaknesses. A large number of participating centers yielded a relatively limited number of study participants: 79% of the centers contributed fewer than two patients, and only the M.D. Anderson center contributed more than three patients. The cancers were mostly adenocarcinomas, but the study included some squamous cell cancers and esophageal or esophagogastric junction tumors – a mixed presentation that makes analysis of results more complex. There were no stage-by-stage comparisons of results, and the study included everything from T2 N0 to T3 N1 stage disease.
In addition, there was no reliable current methodology for accurately identifying complete pathological response without surgical resection. "Remember, that’s the important issue, because at some point you have to sit down with a physiologically intact person and give an impression as to whether they’ve had a complete response," he said.
Dr. Donald Low is head of the section on general thoracic surgery and thoracic oncology at Virginia Mason Medical Center, Seattle. This is a portion of his discussion of Dr. Swisher’s study at the meeting. Dr. Low has received honoraria from Boston Scientific.
This study provides a start toward "what we should be doing in cancer service delivery," which is creating a customized or tailored approach to delivery of services, Dr. Donald Low said. Eliminating esophagectomy when feasible is "probably appropriate, considering the historical perspective of bad outcomes in esophageal resection."
|
Courtesy of the American Society of Clinical Oncology
|
The RTOG 0246 trial addresses an important clinical issue and looks at a new approach of neoadjuvant therapy and selective surgery. One of the study’s strengths is that surveillance was very scheduled and orchestrated – there was a branch point at which the decision was made to have or not have surgery. How that surveillance would fit into real-world practice is unclear and important to consider, he said. The long-term follow-up is another strength of the study.
On the other hand, it has several weaknesses. A large number of participating centers yielded a relatively limited number of study participants: 79% of the centers contributed fewer than two patients, and only the M.D. Anderson center contributed more than three patients. The cancers were mostly adenocarcinomas, but the study included some squamous cell cancers and esophageal or esophagogastric junction tumors – a mixed presentation that makes analysis of results more complex. There were no stage-by-stage comparisons of results, and the study included everything from T2 N0 to T3 N1 stage disease.
In addition, there was no reliable current methodology for accurately identifying complete pathological response without surgical resection. "Remember, that’s the important issue, because at some point you have to sit down with a physiologically intact person and give an impression as to whether they’ve had a complete response," he said.
Dr. Donald Low is head of the section on general thoracic surgery and thoracic oncology at Virginia Mason Medical Center, Seattle. This is a portion of his discussion of Dr. Swisher’s study at the meeting. Dr. Low has received honoraria from Boston Scientific.
SAN FRANCISCO – Five-year survival rates for 41 patients with locoregionally advanced esophageal cancer who underwent induction chemotherapy and definitive chemoradiotherapy were 53% for patients with a clinical complete response who avoided surgery, 33% for patients with suspected residual disease, and 41% for patients with suspected residual disease who were able to undergo surgery.
The multicenter phase II Radiation Therapy Oncology Group (RTOG) 0246 trial suggests that the organ-preserving strategy of selective esophageal resection after definitive chemoradiation can be an effective approach, Dr. Stephen Swisher said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology (ASCO).
Forty-one of the 43 patients enrolled with nonmetastatic resectable esophageal cancer had enough data to be included in the final analysis. Thirty-seven patients completed both induction chemotherapy and definitive chemoradiotherapy. Four patients died from problems associated with treatment (10%), two related to induction chemotherapy, one related to chemoradiation, and one related to surgery.
The overall 5-year survival rate after a median follow-up of 6.7 years was 37% in an intention-to-treat analysis, which is similar to results of trials of other treatment modalities for locoregionally advanced esophageal cancer, he said. Patients with a clinical complete response to chemoradiotherapy had a median survival of 66 months, compared with 15 months for all patients with suspected residual disease and 36 months for patients with suspected residual disease who were able to undergo surgery, reported Dr. Swisher of the University of Texas M.D. Anderson Cancer Center, Houston, and his associates.
During enrollment in 2003-2006, 15 patients came from the M.D. Anderson Cancer Center; 18 other sites contributed 1-3 patients each. Twenty-nine patients had adenocarcinomas (73%). Pretreatment clinical stages were T3 or greater in 31 patients (76%) and N1 in 29 patients (71%).
All underwent two cycles of induction chemotherapy with 5-fluorouracil (5-FU), cisplatin, and paclitaxel, followed by concurrent chemoradiation and daily 5-FU with cisplatin over the first 5 days.
After definitive chemoradiation, patients underwent chest and abdominal imaging to look for residual locoregional disease using CT scans, esophageal ultrasound, and optional PET scans. Those with no suspected residual disease were observed and monitored for recurrence every 3 months for the first 6 months, then every 6 months for the next 18 months, and then yearly. Patients with suspected residual disease were considered for immediate surgery.
Ultimately, 21 patients (51% of the total) underwent surgery: 17 had selective esophagectomies due to suspected residual cancer; 1 patient with a clinical complete response after chemoradiotherapy requested surgery; and 3 patients who were thought to have clinical complete responses underwent salvage esophagectomies due to recurrent cancer 5-15 months after chemoradiotherapy.
Besides the 17 patients with suspected residual cancer who underwent surgery, 4 others with a noncomplete response to chemoradiotherapy did not have esophagectomies because of metastatic disease in 3 patients and inoperable local disease in 1 patient.
The investigators previously reported preliminary results showing an overall 1-year survival rate of 71% in the study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Swisher reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Five-year survival rates for 41 patients with locoregionally advanced esophageal cancer who underwent induction chemotherapy and definitive chemoradiotherapy were 53% for patients with a clinical complete response who avoided surgery, 33% for patients with suspected residual disease, and 41% for patients with suspected residual disease who were able to undergo surgery.
The multicenter phase II Radiation Therapy Oncology Group (RTOG) 0246 trial suggests that the organ-preserving strategy of selective esophageal resection after definitive chemoradiation can be an effective approach, Dr. Stephen Swisher said at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology (ASCO).
Forty-one of the 43 patients enrolled with nonmetastatic resectable esophageal cancer had enough data to be included in the final analysis. Thirty-seven patients completed both induction chemotherapy and definitive chemoradiotherapy. Four patients died from problems associated with treatment (10%), two related to induction chemotherapy, one related to chemoradiation, and one related to surgery.
The overall 5-year survival rate after a median follow-up of 6.7 years was 37% in an intention-to-treat analysis, which is similar to results of trials of other treatment modalities for locoregionally advanced esophageal cancer, he said. Patients with a clinical complete response to chemoradiotherapy had a median survival of 66 months, compared with 15 months for all patients with suspected residual disease and 36 months for patients with suspected residual disease who were able to undergo surgery, reported Dr. Swisher of the University of Texas M.D. Anderson Cancer Center, Houston, and his associates.
During enrollment in 2003-2006, 15 patients came from the M.D. Anderson Cancer Center; 18 other sites contributed 1-3 patients each. Twenty-nine patients had adenocarcinomas (73%). Pretreatment clinical stages were T3 or greater in 31 patients (76%) and N1 in 29 patients (71%).
All underwent two cycles of induction chemotherapy with 5-fluorouracil (5-FU), cisplatin, and paclitaxel, followed by concurrent chemoradiation and daily 5-FU with cisplatin over the first 5 days.
After definitive chemoradiation, patients underwent chest and abdominal imaging to look for residual locoregional disease using CT scans, esophageal ultrasound, and optional PET scans. Those with no suspected residual disease were observed and monitored for recurrence every 3 months for the first 6 months, then every 6 months for the next 18 months, and then yearly. Patients with suspected residual disease were considered for immediate surgery.
Ultimately, 21 patients (51% of the total) underwent surgery: 17 had selective esophagectomies due to suspected residual cancer; 1 patient with a clinical complete response after chemoradiotherapy requested surgery; and 3 patients who were thought to have clinical complete responses underwent salvage esophagectomies due to recurrent cancer 5-15 months after chemoradiotherapy.
Besides the 17 patients with suspected residual cancer who underwent surgery, 4 others with a noncomplete response to chemoradiotherapy did not have esophagectomies because of metastatic disease in 3 patients and inoperable local disease in 1 patient.
The investigators previously reported preliminary results showing an overall 1-year survival rate of 71% in the study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Swisher reported having no financial disclosures.
On Twitter @sherryboschert
AT THE ASCO GASTROINTESTINAL CANCERS SYMPOSIUM
Major finding: Five-year survival rates after definitive chemoradiotherapy were 53% with complete clinical responses to definitive chemoradiotherapy, 33% for those with noncomplete responses, and 41% for patients in the latter group who were able to undergo esophagectomy.
Data source: Prospective multicenter trial of selective surgery following definitive chemoradiotherapy in 41 patients with advanced locoregional esophageal cancer.
Disclosures: Dr. Swisher reported having no financial disclosures.
Racial gap in gastric cancer survival narrows at 3 years
Race is a significant predictor of the odds of surviving gastric cancer at the time of diagnosis: Its impact lessens the longer the patient survives, an analysis of data on 24,657 patients who underwent potentially curative surgery suggests.
At the time of diagnosis, estimates of 3-year relative conditional survival rates were significantly different by race. Asian patients (17% of the cohort) had a 3-year relative conditional survival of 52%, compared with 42% for black patients (14% of the cohort), and 41% for white patients (69% of the cohort), Dr. David T. Luyimbazi and his associates reported.
For patients who were still alive 3 years after diagnosis, the estimates that they would survive another 3 years improved in each group, and the racial gap narrowed significantly and nearly disappeared. Three-year relative conditional survival rates were 83% for Asian patients, 82% for black patients, and 78% for white patients, Dr. Luyimbazi said in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
His study won a Merit Award at the meeting.
The investigators analyzed data from the Surveillance, Epidemiology and End Results (SEER) registry on patients with gastric cancer who were treated with curative surgery from 1988 to 2006.
Conditional survival analyses estimate a patient’s probability of surviving for a specified time given that the patient already has survived a specified time after diagnosis. In patients with gastric cancer, conditional survival estimates rely on disease staging, pathological tumor characteristics, and a variety of clinical factors. These estimates do not typically include the influence of racial disparities, even though previous studies have shown that racial disparities are a predictor of survival, independent of clinical or pathological features, said Dr. Luyimbazi, a surgical oncology fellow at City of Hope National Medical Center, Duarte, Calif.
Conditional survival can be a "confusing concept" but it’s gradually being embraced by oncologists because it makes sense that a patient’s prognosis at the time of diagnosis is not the same after the patient has survived a year or 2 or 3 years longer, he said in an interview.
Eventually, it may be possible to create a nomogram so that physicians can use a particular patient’s characteristics to estimate how much longer the patient might live, given how long the that person has lived since diagnosis, he suggested. A clinician might be able to suggest to a patient who has been followed every 6 months for the last 3 years that follow-up intervals be lengthened or shortened, depending on any change in conditional survival, Dr. Luyimbazi said. And if a patient reaches a point at which the estimated conditional survival is the same as it was before being diagnosed with cancer, the patient might revert to the same surveillance schedules used for the general population.
Conditional survival was reported in the study as a relative conditional survival rate, which is the observed conditional survival rate divided by the expected conditional survival rate from a general population that is matched to the study cohort by age, sex, and race.
One year after diagnosis, the 3-year relative conditional survival rates increased to 64% for Asian patients, 56% for black patients, and 55% for white patients. By 2 years after diagnosis, the 3-year relative conditional survival rates were 76% for Asian patients, 71% for black patients, and 68% for white patients. Rates improved further, and the racial gap narrowed even more, by the third year after diagnosis.
Dr. Luyimbazi reported having no financial disclosures.
On Twitter @sherryboschert
Race is a significant predictor of the odds of surviving gastric cancer at the time of diagnosis: Its impact lessens the longer the patient survives, an analysis of data on 24,657 patients who underwent potentially curative surgery suggests.
At the time of diagnosis, estimates of 3-year relative conditional survival rates were significantly different by race. Asian patients (17% of the cohort) had a 3-year relative conditional survival of 52%, compared with 42% for black patients (14% of the cohort), and 41% for white patients (69% of the cohort), Dr. David T. Luyimbazi and his associates reported.
For patients who were still alive 3 years after diagnosis, the estimates that they would survive another 3 years improved in each group, and the racial gap narrowed significantly and nearly disappeared. Three-year relative conditional survival rates were 83% for Asian patients, 82% for black patients, and 78% for white patients, Dr. Luyimbazi said in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
His study won a Merit Award at the meeting.
The investigators analyzed data from the Surveillance, Epidemiology and End Results (SEER) registry on patients with gastric cancer who were treated with curative surgery from 1988 to 2006.
Conditional survival analyses estimate a patient’s probability of surviving for a specified time given that the patient already has survived a specified time after diagnosis. In patients with gastric cancer, conditional survival estimates rely on disease staging, pathological tumor characteristics, and a variety of clinical factors. These estimates do not typically include the influence of racial disparities, even though previous studies have shown that racial disparities are a predictor of survival, independent of clinical or pathological features, said Dr. Luyimbazi, a surgical oncology fellow at City of Hope National Medical Center, Duarte, Calif.
Conditional survival can be a "confusing concept" but it’s gradually being embraced by oncologists because it makes sense that a patient’s prognosis at the time of diagnosis is not the same after the patient has survived a year or 2 or 3 years longer, he said in an interview.
Eventually, it may be possible to create a nomogram so that physicians can use a particular patient’s characteristics to estimate how much longer the patient might live, given how long the that person has lived since diagnosis, he suggested. A clinician might be able to suggest to a patient who has been followed every 6 months for the last 3 years that follow-up intervals be lengthened or shortened, depending on any change in conditional survival, Dr. Luyimbazi said. And if a patient reaches a point at which the estimated conditional survival is the same as it was before being diagnosed with cancer, the patient might revert to the same surveillance schedules used for the general population.
Conditional survival was reported in the study as a relative conditional survival rate, which is the observed conditional survival rate divided by the expected conditional survival rate from a general population that is matched to the study cohort by age, sex, and race.
One year after diagnosis, the 3-year relative conditional survival rates increased to 64% for Asian patients, 56% for black patients, and 55% for white patients. By 2 years after diagnosis, the 3-year relative conditional survival rates were 76% for Asian patients, 71% for black patients, and 68% for white patients. Rates improved further, and the racial gap narrowed even more, by the third year after diagnosis.
Dr. Luyimbazi reported having no financial disclosures.
On Twitter @sherryboschert
Race is a significant predictor of the odds of surviving gastric cancer at the time of diagnosis: Its impact lessens the longer the patient survives, an analysis of data on 24,657 patients who underwent potentially curative surgery suggests.
At the time of diagnosis, estimates of 3-year relative conditional survival rates were significantly different by race. Asian patients (17% of the cohort) had a 3-year relative conditional survival of 52%, compared with 42% for black patients (14% of the cohort), and 41% for white patients (69% of the cohort), Dr. David T. Luyimbazi and his associates reported.
For patients who were still alive 3 years after diagnosis, the estimates that they would survive another 3 years improved in each group, and the racial gap narrowed significantly and nearly disappeared. Three-year relative conditional survival rates were 83% for Asian patients, 82% for black patients, and 78% for white patients, Dr. Luyimbazi said in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
His study won a Merit Award at the meeting.
The investigators analyzed data from the Surveillance, Epidemiology and End Results (SEER) registry on patients with gastric cancer who were treated with curative surgery from 1988 to 2006.
Conditional survival analyses estimate a patient’s probability of surviving for a specified time given that the patient already has survived a specified time after diagnosis. In patients with gastric cancer, conditional survival estimates rely on disease staging, pathological tumor characteristics, and a variety of clinical factors. These estimates do not typically include the influence of racial disparities, even though previous studies have shown that racial disparities are a predictor of survival, independent of clinical or pathological features, said Dr. Luyimbazi, a surgical oncology fellow at City of Hope National Medical Center, Duarte, Calif.
Conditional survival can be a "confusing concept" but it’s gradually being embraced by oncologists because it makes sense that a patient’s prognosis at the time of diagnosis is not the same after the patient has survived a year or 2 or 3 years longer, he said in an interview.
Eventually, it may be possible to create a nomogram so that physicians can use a particular patient’s characteristics to estimate how much longer the patient might live, given how long the that person has lived since diagnosis, he suggested. A clinician might be able to suggest to a patient who has been followed every 6 months for the last 3 years that follow-up intervals be lengthened or shortened, depending on any change in conditional survival, Dr. Luyimbazi said. And if a patient reaches a point at which the estimated conditional survival is the same as it was before being diagnosed with cancer, the patient might revert to the same surveillance schedules used for the general population.
Conditional survival was reported in the study as a relative conditional survival rate, which is the observed conditional survival rate divided by the expected conditional survival rate from a general population that is matched to the study cohort by age, sex, and race.
One year after diagnosis, the 3-year relative conditional survival rates increased to 64% for Asian patients, 56% for black patients, and 55% for white patients. By 2 years after diagnosis, the 3-year relative conditional survival rates were 76% for Asian patients, 71% for black patients, and 68% for white patients. Rates improved further, and the racial gap narrowed even more, by the third year after diagnosis.
Dr. Luyimbazi reported having no financial disclosures.
On Twitter @sherryboschert
AT A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Three-year relative conditional survival rates for Asian, black, or white patients with gastric cancer who underwent curative surgery improved from 52%, 42%, and 41% at baseline, respectively, to 83%, 82% and 78%, respectively, 3 years later.
Data Source: Retrospective analysis of SEER registry data on 24,657 patients with gastric cancer treated with potentially curative surgery.
Disclosures: Dr. Luyimbazi reported having no financial disclosures.
Capecitabine chemoradiotherapy effective in local pancreatic cancer
SAN FRANCISCO – Following induction chemotherapy with radiotherapy plus capecitabine seemed to be equally effective and less toxic compared with following with radiotherapy plus gemcitabine in a randomized trial of 74 patients with locally advanced pancreatic cancer.
The multicenter phase II clinical trial randomized 36 patients to radiotherapy plus capecitabine (Xeloda, Roche/Genentech) and 38 to radiotherapy plus gemcitabine (Gemzar, Eli Lilly) after induction chemotherapy. Analysis of the primary outcome, progression-free survival after 9 months, included 35 evaluable patients in each group. No disease progression was noted in 62% of patients in the capecitabine-radiotherapy arm and in 51% in the gemcitabine-radiotherapy arm, Dr. Somnath Mukherjee reported.
The median time to disease progression was 12 months in patients given capecitabine-radiotherapy and 10.4 months in those given gemcitabine-radiotherapy. The differences between groups in progression-free survival were not statistically significant, Dr. Mukherjee and his associates said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Based on secondary outcomes, however, capecitabine-radiotherapy seemed to show some advantages, including less toxicity and improved overall survival, said Dr. Mukherjee of the University of Oxford, England.
None of the patients in the capecitabine-radiotherapy arm and 18% of those in the gemcitabine-radiotherapy arm had grade 3 or 4 hematologic adverse events. The rates of nonhematologic adverse events were similarly lower with capecitabine-radiotherapy, 12%, than with gemcitabine-radiotherapy, 26%. Median overall survival was 15.2 months in the capecitabine-radiotherapy group and 13.4 months in the gemcitabine-radiotherapy group.
There is no consensus on the optimal treatment for locally advanced pancreatic cancer, Dr. Mukherjee said. Previous trials of chemotherapy alone or chemoradiotherapy suggest a median survival of 10 months. One meta-analysis suggested that gemcitabine-based chemoradiotherapy might be more effective but also more toxic compared with chemoradiotherapy based on 5-fluoruracil. No prior study has compared gemcitabine-radiotherapy with capecitabine-radiotherapy, he added.
The study, known as the SCALOP trial, initially registered 114 patients, but excluded 40 patients from randomization due to disease progression (15 patients), the clinician’s decision (10 patients), the patient’s decision (9), death (5), or because the patient shouldn’t have been eligible for the trial (1). Among randomized patients, median overall survival was 14.6 months, and 78% were alive after 1 year. Among nonrandomized patients, median survival was 8.1 months, and 17% were alive at 1 year.
All 114 registered patients were to receive three cycles of induction chemotherapy with gemcitabine plus capecitabine. The investigators then randomized 74 patients to the two groups, all of whom received another cycle of gemcitabine-capecitabine chemotherapy before starting radiation therapy plus either gemcitabine or capecitabine.
Among 35 patients on capecitabine-radiotherapy and 36 on gemcitabine-radiotherapy who had follow-up data at 26 weeks, the pancreatic cancer showed a complete response, partial response, or stable disease in 86% of each treatment group. The proportions of patients who became eligible for surgical resection after radiotherapy were 6% in the capecitabine group and 10% in the gemcitabine group.
Any kind of grade 3 or 4 toxicities occurred in 12% on capecitabine-radiotherapy and in 37% on gemcitabine-chemotherapy.
Males comprised 47% of the capecitabine-radiotherapy arm and 63% of the gemcitabine-radiotherapy arm. The median patient age was 63 years in the capecitabine group and 66 years in the gemcitabine group.
Meeting cosponsors were the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Sanofi, or Roche, which markets capecitabine through its subsidiary, Genentech.
On Twitter @sherryboschert
The primary endpoint of this study was progression-free survival at 9 months, but keep in mind that all the patients received the same induction chemotherapy for 4 months, and the same radiotherapy dose, but with the sole difference of being either on capecitabine or low-dose gemcitabine during the 6 weeks of radiotherapy. The use of this primary endpoint, therefore, challenges our ability to properly ask a regular standardization question and must make us think about how best to choose endpoints that are more informative in this multimodality treatment setting in a complex disease.
The efficacy and toxicity parameters favored capecitabine. The impact of subject selection is beautifully illustrated by a table that showed almost doubling in survival in patients who made it to randomization versus those who were taken off the study.
What does SCALOP tell us? The major take-home message confirms the feasibility of the common practice of using capecitabine concurrently with radiotherapy in patients with pancreatic cancer. A number of other factors may have contributed to the differences in outcome, such as proportion of males to females. Several important questions remain in this disease, including the role of chemoradiation.
Ultimately we have to find better systemic therapies. However, one of the most important things in my mind is that we have to design trials to include primary endpoints that stick with the question we are asking. There are different questions we can ask in pancreatic cancer, but each question should have a specific design and a specific endpoint.
Dr. Philip A. Philip is leader of the gastrointestinal cancer multidisciplinary team, and a professor of medicine and oncology, at Wayne State University, Detroit. These were among his comments as discussant of Dr. Mukherjee’s study at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies including Eli Lilly, Roche, and Genentech.
The primary endpoint of this study was progression-free survival at 9 months, but keep in mind that all the patients received the same induction chemotherapy for 4 months, and the same radiotherapy dose, but with the sole difference of being either on capecitabine or low-dose gemcitabine during the 6 weeks of radiotherapy. The use of this primary endpoint, therefore, challenges our ability to properly ask a regular standardization question and must make us think about how best to choose endpoints that are more informative in this multimodality treatment setting in a complex disease.
The efficacy and toxicity parameters favored capecitabine. The impact of subject selection is beautifully illustrated by a table that showed almost doubling in survival in patients who made it to randomization versus those who were taken off the study.
What does SCALOP tell us? The major take-home message confirms the feasibility of the common practice of using capecitabine concurrently with radiotherapy in patients with pancreatic cancer. A number of other factors may have contributed to the differences in outcome, such as proportion of males to females. Several important questions remain in this disease, including the role of chemoradiation.
Ultimately we have to find better systemic therapies. However, one of the most important things in my mind is that we have to design trials to include primary endpoints that stick with the question we are asking. There are different questions we can ask in pancreatic cancer, but each question should have a specific design and a specific endpoint.
Dr. Philip A. Philip is leader of the gastrointestinal cancer multidisciplinary team, and a professor of medicine and oncology, at Wayne State University, Detroit. These were among his comments as discussant of Dr. Mukherjee’s study at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies including Eli Lilly, Roche, and Genentech.
The primary endpoint of this study was progression-free survival at 9 months, but keep in mind that all the patients received the same induction chemotherapy for 4 months, and the same radiotherapy dose, but with the sole difference of being either on capecitabine or low-dose gemcitabine during the 6 weeks of radiotherapy. The use of this primary endpoint, therefore, challenges our ability to properly ask a regular standardization question and must make us think about how best to choose endpoints that are more informative in this multimodality treatment setting in a complex disease.
The efficacy and toxicity parameters favored capecitabine. The impact of subject selection is beautifully illustrated by a table that showed almost doubling in survival in patients who made it to randomization versus those who were taken off the study.
What does SCALOP tell us? The major take-home message confirms the feasibility of the common practice of using capecitabine concurrently with radiotherapy in patients with pancreatic cancer. A number of other factors may have contributed to the differences in outcome, such as proportion of males to females. Several important questions remain in this disease, including the role of chemoradiation.
Ultimately we have to find better systemic therapies. However, one of the most important things in my mind is that we have to design trials to include primary endpoints that stick with the question we are asking. There are different questions we can ask in pancreatic cancer, but each question should have a specific design and a specific endpoint.
Dr. Philip A. Philip is leader of the gastrointestinal cancer multidisciplinary team, and a professor of medicine and oncology, at Wayne State University, Detroit. These were among his comments as discussant of Dr. Mukherjee’s study at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies including Eli Lilly, Roche, and Genentech.
SAN FRANCISCO – Following induction chemotherapy with radiotherapy plus capecitabine seemed to be equally effective and less toxic compared with following with radiotherapy plus gemcitabine in a randomized trial of 74 patients with locally advanced pancreatic cancer.
The multicenter phase II clinical trial randomized 36 patients to radiotherapy plus capecitabine (Xeloda, Roche/Genentech) and 38 to radiotherapy plus gemcitabine (Gemzar, Eli Lilly) after induction chemotherapy. Analysis of the primary outcome, progression-free survival after 9 months, included 35 evaluable patients in each group. No disease progression was noted in 62% of patients in the capecitabine-radiotherapy arm and in 51% in the gemcitabine-radiotherapy arm, Dr. Somnath Mukherjee reported.
The median time to disease progression was 12 months in patients given capecitabine-radiotherapy and 10.4 months in those given gemcitabine-radiotherapy. The differences between groups in progression-free survival were not statistically significant, Dr. Mukherjee and his associates said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Based on secondary outcomes, however, capecitabine-radiotherapy seemed to show some advantages, including less toxicity and improved overall survival, said Dr. Mukherjee of the University of Oxford, England.
None of the patients in the capecitabine-radiotherapy arm and 18% of those in the gemcitabine-radiotherapy arm had grade 3 or 4 hematologic adverse events. The rates of nonhematologic adverse events were similarly lower with capecitabine-radiotherapy, 12%, than with gemcitabine-radiotherapy, 26%. Median overall survival was 15.2 months in the capecitabine-radiotherapy group and 13.4 months in the gemcitabine-radiotherapy group.
There is no consensus on the optimal treatment for locally advanced pancreatic cancer, Dr. Mukherjee said. Previous trials of chemotherapy alone or chemoradiotherapy suggest a median survival of 10 months. One meta-analysis suggested that gemcitabine-based chemoradiotherapy might be more effective but also more toxic compared with chemoradiotherapy based on 5-fluoruracil. No prior study has compared gemcitabine-radiotherapy with capecitabine-radiotherapy, he added.
The study, known as the SCALOP trial, initially registered 114 patients, but excluded 40 patients from randomization due to disease progression (15 patients), the clinician’s decision (10 patients), the patient’s decision (9), death (5), or because the patient shouldn’t have been eligible for the trial (1). Among randomized patients, median overall survival was 14.6 months, and 78% were alive after 1 year. Among nonrandomized patients, median survival was 8.1 months, and 17% were alive at 1 year.
All 114 registered patients were to receive three cycles of induction chemotherapy with gemcitabine plus capecitabine. The investigators then randomized 74 patients to the two groups, all of whom received another cycle of gemcitabine-capecitabine chemotherapy before starting radiation therapy plus either gemcitabine or capecitabine.
Among 35 patients on capecitabine-radiotherapy and 36 on gemcitabine-radiotherapy who had follow-up data at 26 weeks, the pancreatic cancer showed a complete response, partial response, or stable disease in 86% of each treatment group. The proportions of patients who became eligible for surgical resection after radiotherapy were 6% in the capecitabine group and 10% in the gemcitabine group.
Any kind of grade 3 or 4 toxicities occurred in 12% on capecitabine-radiotherapy and in 37% on gemcitabine-chemotherapy.
Males comprised 47% of the capecitabine-radiotherapy arm and 63% of the gemcitabine-radiotherapy arm. The median patient age was 63 years in the capecitabine group and 66 years in the gemcitabine group.
Meeting cosponsors were the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Sanofi, or Roche, which markets capecitabine through its subsidiary, Genentech.
On Twitter @sherryboschert
SAN FRANCISCO – Following induction chemotherapy with radiotherapy plus capecitabine seemed to be equally effective and less toxic compared with following with radiotherapy plus gemcitabine in a randomized trial of 74 patients with locally advanced pancreatic cancer.
The multicenter phase II clinical trial randomized 36 patients to radiotherapy plus capecitabine (Xeloda, Roche/Genentech) and 38 to radiotherapy plus gemcitabine (Gemzar, Eli Lilly) after induction chemotherapy. Analysis of the primary outcome, progression-free survival after 9 months, included 35 evaluable patients in each group. No disease progression was noted in 62% of patients in the capecitabine-radiotherapy arm and in 51% in the gemcitabine-radiotherapy arm, Dr. Somnath Mukherjee reported.
The median time to disease progression was 12 months in patients given capecitabine-radiotherapy and 10.4 months in those given gemcitabine-radiotherapy. The differences between groups in progression-free survival were not statistically significant, Dr. Mukherjee and his associates said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Based on secondary outcomes, however, capecitabine-radiotherapy seemed to show some advantages, including less toxicity and improved overall survival, said Dr. Mukherjee of the University of Oxford, England.
None of the patients in the capecitabine-radiotherapy arm and 18% of those in the gemcitabine-radiotherapy arm had grade 3 or 4 hematologic adverse events. The rates of nonhematologic adverse events were similarly lower with capecitabine-radiotherapy, 12%, than with gemcitabine-radiotherapy, 26%. Median overall survival was 15.2 months in the capecitabine-radiotherapy group and 13.4 months in the gemcitabine-radiotherapy group.
There is no consensus on the optimal treatment for locally advanced pancreatic cancer, Dr. Mukherjee said. Previous trials of chemotherapy alone or chemoradiotherapy suggest a median survival of 10 months. One meta-analysis suggested that gemcitabine-based chemoradiotherapy might be more effective but also more toxic compared with chemoradiotherapy based on 5-fluoruracil. No prior study has compared gemcitabine-radiotherapy with capecitabine-radiotherapy, he added.
The study, known as the SCALOP trial, initially registered 114 patients, but excluded 40 patients from randomization due to disease progression (15 patients), the clinician’s decision (10 patients), the patient’s decision (9), death (5), or because the patient shouldn’t have been eligible for the trial (1). Among randomized patients, median overall survival was 14.6 months, and 78% were alive after 1 year. Among nonrandomized patients, median survival was 8.1 months, and 17% were alive at 1 year.
All 114 registered patients were to receive three cycles of induction chemotherapy with gemcitabine plus capecitabine. The investigators then randomized 74 patients to the two groups, all of whom received another cycle of gemcitabine-capecitabine chemotherapy before starting radiation therapy plus either gemcitabine or capecitabine.
Among 35 patients on capecitabine-radiotherapy and 36 on gemcitabine-radiotherapy who had follow-up data at 26 weeks, the pancreatic cancer showed a complete response, partial response, or stable disease in 86% of each treatment group. The proportions of patients who became eligible for surgical resection after radiotherapy were 6% in the capecitabine group and 10% in the gemcitabine group.
Any kind of grade 3 or 4 toxicities occurred in 12% on capecitabine-radiotherapy and in 37% on gemcitabine-chemotherapy.
Males comprised 47% of the capecitabine-radiotherapy arm and 63% of the gemcitabine-radiotherapy arm. The median patient age was 63 years in the capecitabine group and 66 years in the gemcitabine group.
Meeting cosponsors were the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Sanofi, or Roche, which markets capecitabine through its subsidiary, Genentech.
On Twitter @sherryboschert
AT A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Median progression-free survival after 9 months of follow-up was 12 months in 35 patients given capecitabine plus radiotherapy after induction chemotherapy and 10.4 months in patients given gemcitabine plus radiotherapy following induction chemotherapy.
Data Source: A multicenter trial that randomized 74 patients with locally advanced pancreatic cancer.
Disclosures: Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Roche, or Sanofi.
Beware of subgroup analyses in trial results
Studies often include subgroup analyses outlining how a specific treatment is more or less effective in one group of patients compared with another. But clinicians, beware: Subgroup analyses too often are not clinically meaningful and should be interpreted cautiously, Dr. Sarah R. Barton and her associates reported in a poster presentation at the American Society for Clinical Oncology’s Gastrointestinal Cancers Symposium.
The investigators reviewed 145 randomized, controlled phase III trials published in peer-reviewed journals from January 2003 to January 2012 that tested an investigational therapy in GI cancer and that involved at least 150 patients. Subgroup analyses appeared in 100 studies (69%), more often in larger ones.
Here’s the shocking part: Only 25% of trials that claimed the treatment worked in a subgroup of patients had the statistical measures to back that up, reported Dr. Barton of Royal Marsden Hospital, Sutton, England. That proportion was the same for industry-sponsored and nonindustry trials.
The study, which won a Merit Award at the meeting, conducted some interesting subgroup analyses of its own. Trials sponsored by for-profit companies included a significantly higher number of subgroup analyses compared with nonindustry trials – a median of six versus two, respectively.
Trials of targeted therapies were more than three times as likely to report subgroup analyses compared with studies of cytotoxic therapies and included significantly more subgroup analyses (a median of six vs. two, respectively). Studies that reported a positive effect in the primary outcome also included a significantly higher median number of subgroup analyses compared with negative trials (again, six versus two).
Industry-sponsored trials that reported a positive effect in the primary outcome of the study were the most likely to report subgroup analyses (23 of 25 studies, or 95%) and to include the highest median number of subgroup analyses (eight) compared with industry-funded trials with a negative primary outcome or nonindustry trials, positive or negative.
Dr. Barton gave some clues that, in general, should cause physicians to look closely at efficacy claims. These include subgroup analyses conducted post hoc, when multiple tests are applied, when multiple endpoints are used, and if there’s no statistically significant test of interaction.
This is not just a problem in oncology. A previous study of 469 randomized, controlled trials published in 118 journals reported that industry-funded trials were less likely to define subgroups before starting the trial, less likely to use the interaction test for analyses of subgroup effects, and more likely to report on subgroups if the primary outcome in the study did not show a positive result (BMJ 2011;342:d1569)
The New England Journal of Medicine provides similar cautions in its guidelines for investigators reporting on subgroup analyses (N. Engl. J. Med. 2007;357:2189-2194).
Dr. Barton reported having no financial disclosures.
– Sherry Boschert
On Twitter @sherryboschert
Studies often include subgroup analyses outlining how a specific treatment is more or less effective in one group of patients compared with another. But clinicians, beware: Subgroup analyses too often are not clinically meaningful and should be interpreted cautiously, Dr. Sarah R. Barton and her associates reported in a poster presentation at the American Society for Clinical Oncology’s Gastrointestinal Cancers Symposium.
The investigators reviewed 145 randomized, controlled phase III trials published in peer-reviewed journals from January 2003 to January 2012 that tested an investigational therapy in GI cancer and that involved at least 150 patients. Subgroup analyses appeared in 100 studies (69%), more often in larger ones.
Here’s the shocking part: Only 25% of trials that claimed the treatment worked in a subgroup of patients had the statistical measures to back that up, reported Dr. Barton of Royal Marsden Hospital, Sutton, England. That proportion was the same for industry-sponsored and nonindustry trials.
The study, which won a Merit Award at the meeting, conducted some interesting subgroup analyses of its own. Trials sponsored by for-profit companies included a significantly higher number of subgroup analyses compared with nonindustry trials – a median of six versus two, respectively.
Trials of targeted therapies were more than three times as likely to report subgroup analyses compared with studies of cytotoxic therapies and included significantly more subgroup analyses (a median of six vs. two, respectively). Studies that reported a positive effect in the primary outcome also included a significantly higher median number of subgroup analyses compared with negative trials (again, six versus two).
Industry-sponsored trials that reported a positive effect in the primary outcome of the study were the most likely to report subgroup analyses (23 of 25 studies, or 95%) and to include the highest median number of subgroup analyses (eight) compared with industry-funded trials with a negative primary outcome or nonindustry trials, positive or negative.
Dr. Barton gave some clues that, in general, should cause physicians to look closely at efficacy claims. These include subgroup analyses conducted post hoc, when multiple tests are applied, when multiple endpoints are used, and if there’s no statistically significant test of interaction.
This is not just a problem in oncology. A previous study of 469 randomized, controlled trials published in 118 journals reported that industry-funded trials were less likely to define subgroups before starting the trial, less likely to use the interaction test for analyses of subgroup effects, and more likely to report on subgroups if the primary outcome in the study did not show a positive result (BMJ 2011;342:d1569)
The New England Journal of Medicine provides similar cautions in its guidelines for investigators reporting on subgroup analyses (N. Engl. J. Med. 2007;357:2189-2194).
Dr. Barton reported having no financial disclosures.
– Sherry Boschert
On Twitter @sherryboschert
Studies often include subgroup analyses outlining how a specific treatment is more or less effective in one group of patients compared with another. But clinicians, beware: Subgroup analyses too often are not clinically meaningful and should be interpreted cautiously, Dr. Sarah R. Barton and her associates reported in a poster presentation at the American Society for Clinical Oncology’s Gastrointestinal Cancers Symposium.
The investigators reviewed 145 randomized, controlled phase III trials published in peer-reviewed journals from January 2003 to January 2012 that tested an investigational therapy in GI cancer and that involved at least 150 patients. Subgroup analyses appeared in 100 studies (69%), more often in larger ones.
Here’s the shocking part: Only 25% of trials that claimed the treatment worked in a subgroup of patients had the statistical measures to back that up, reported Dr. Barton of Royal Marsden Hospital, Sutton, England. That proportion was the same for industry-sponsored and nonindustry trials.
The study, which won a Merit Award at the meeting, conducted some interesting subgroup analyses of its own. Trials sponsored by for-profit companies included a significantly higher number of subgroup analyses compared with nonindustry trials – a median of six versus two, respectively.
Trials of targeted therapies were more than three times as likely to report subgroup analyses compared with studies of cytotoxic therapies and included significantly more subgroup analyses (a median of six vs. two, respectively). Studies that reported a positive effect in the primary outcome also included a significantly higher median number of subgroup analyses compared with negative trials (again, six versus two).
Industry-sponsored trials that reported a positive effect in the primary outcome of the study were the most likely to report subgroup analyses (23 of 25 studies, or 95%) and to include the highest median number of subgroup analyses (eight) compared with industry-funded trials with a negative primary outcome or nonindustry trials, positive or negative.
Dr. Barton gave some clues that, in general, should cause physicians to look closely at efficacy claims. These include subgroup analyses conducted post hoc, when multiple tests are applied, when multiple endpoints are used, and if there’s no statistically significant test of interaction.
This is not just a problem in oncology. A previous study of 469 randomized, controlled trials published in 118 journals reported that industry-funded trials were less likely to define subgroups before starting the trial, less likely to use the interaction test for analyses of subgroup effects, and more likely to report on subgroups if the primary outcome in the study did not show a positive result (BMJ 2011;342:d1569)
The New England Journal of Medicine provides similar cautions in its guidelines for investigators reporting on subgroup analyses (N. Engl. J. Med. 2007;357:2189-2194).
Dr. Barton reported having no financial disclosures.
– Sherry Boschert
On Twitter @sherryboschert
Survival shorter in young gastric cancer patients
Patients with gastric adenocarcinoma who were diagnosed before age 40 years died significantly sooner than did older patients, based on the results of a single-center, retrospective study of 520 cases.
Patients diagnosed before age 40 survived a median of 5 months after diagnosis; 24% were alive at 1 year. Older patients survived a median of 8 months, and 39% were alive at 1 year, reported Dr. Bryan Goldner and his associates.
Surgical exploration was often futile in the younger patients, said Dr. Goldner of Harbor-UCLA Medical Center in Torrance, Calif. Surgery removed all tumors with histologically free margins (R0 resection) in 33% of younger patients, compared with 60% of older patients, he reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Recent reports in the medical literature suggest that younger patients with gastric adenocarcinoma are more likely to be diagnosed with node-positive and metastatic disease. One retrospective study of 350 patients found that younger patients had more aggressive gastric adenocarcinomas and died sooner than older patients (Arch. Surg. 2009;144:506-10).
A separate retrospective study of 33,236 U.S. patients found that younger patients presented with more advanced gastric adenocarcinoma but had better survival outcomes than older patients when stratified by disease stage (Ann. Surg. Oncol. 2011;18:2800-7).
Gastric cancer might not be suspected in younger patients, which could result in young patients going undiagnosed until their cancers are more advanced, Dr. Goldner suggested.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Goldner reported having no financial disclosures.
On Twitter @sherryboschert
Patients with gastric adenocarcinoma who were diagnosed before age 40 years died significantly sooner than did older patients, based on the results of a single-center, retrospective study of 520 cases.
Patients diagnosed before age 40 survived a median of 5 months after diagnosis; 24% were alive at 1 year. Older patients survived a median of 8 months, and 39% were alive at 1 year, reported Dr. Bryan Goldner and his associates.
Surgical exploration was often futile in the younger patients, said Dr. Goldner of Harbor-UCLA Medical Center in Torrance, Calif. Surgery removed all tumors with histologically free margins (R0 resection) in 33% of younger patients, compared with 60% of older patients, he reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Recent reports in the medical literature suggest that younger patients with gastric adenocarcinoma are more likely to be diagnosed with node-positive and metastatic disease. One retrospective study of 350 patients found that younger patients had more aggressive gastric adenocarcinomas and died sooner than older patients (Arch. Surg. 2009;144:506-10).
A separate retrospective study of 33,236 U.S. patients found that younger patients presented with more advanced gastric adenocarcinoma but had better survival outcomes than older patients when stratified by disease stage (Ann. Surg. Oncol. 2011;18:2800-7).
Gastric cancer might not be suspected in younger patients, which could result in young patients going undiagnosed until their cancers are more advanced, Dr. Goldner suggested.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Goldner reported having no financial disclosures.
On Twitter @sherryboschert
Patients with gastric adenocarcinoma who were diagnosed before age 40 years died significantly sooner than did older patients, based on the results of a single-center, retrospective study of 520 cases.
Patients diagnosed before age 40 survived a median of 5 months after diagnosis; 24% were alive at 1 year. Older patients survived a median of 8 months, and 39% were alive at 1 year, reported Dr. Bryan Goldner and his associates.
Surgical exploration was often futile in the younger patients, said Dr. Goldner of Harbor-UCLA Medical Center in Torrance, Calif. Surgery removed all tumors with histologically free margins (R0 resection) in 33% of younger patients, compared with 60% of older patients, he reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Recent reports in the medical literature suggest that younger patients with gastric adenocarcinoma are more likely to be diagnosed with node-positive and metastatic disease. One retrospective study of 350 patients found that younger patients had more aggressive gastric adenocarcinomas and died sooner than older patients (Arch. Surg. 2009;144:506-10).
A separate retrospective study of 33,236 U.S. patients found that younger patients presented with more advanced gastric adenocarcinoma but had better survival outcomes than older patients when stratified by disease stage (Ann. Surg. Oncol. 2011;18:2800-7).
Gastric cancer might not be suspected in younger patients, which could result in young patients going undiagnosed until their cancers are more advanced, Dr. Goldner suggested.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Goldner reported having no financial disclosures.
On Twitter @sherryboschert
AT A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Patients diagnosed with gastric adenocarcinoma before age 40 years lived a median of 5 months; older patients lived a median of 8 months.
Data Source: Retrospective study of 520 patients with gastric cancer at one public hospital.
Disclosures: Dr. Goldner reported having no financial disclosures.
Gene profiling predicted responses to colorectal, pancreatic cancer treatment
SAN FRANCISCO – Gene expression profiling of patients with colorectal cancer and pharmacogenomic modeling of patients with pancreatic cancer could help identify which patients will respond to particular chemotherapies, preliminary evidence from two small studies suggests.
Spanish investigators developed a molecular classification system using gene expression data from 188 patients with colorectal cancer to identify three subtypes of the cancer, which they called subtypes A, B and C. They then performed a multicenter validation study using tumor samples from 543 patients with stage II and III colorectal cancer, and classified 35% of samples as subtype A, 50% as subtype B, and 15% as subtype C.
They found that the different subtypes were associated with different clinical and biological characteristics and helped predict response to adjuvant chemotherapy regimens based on 5-fluorouracil (5-FU) when compared with 10 years of patient records, Dr. Josep Tabernero and his associates reported at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium.
Patients with subtype C colorectal cancer had a mesenchymal gene expression phenotype and did not respond to 5-FU–based chemotherapy, suggesting that new, targeted treatments need to be found for these tumors, said Dr. Tabernero, director of clinical research at Vall d’Hebron Institute of Oncology, Barcelona.
Patients with subtype A colorectal cancer had the best prognosis – "some of them don’t even need adjuvant therapy," he said in a separate press briefing – and did respond to 5-FU–based chemotherapy. Patients with subtype B had a poor prognosis but showed an even more dramatic response to adjuvant chemotherapy.
Subtypes A and B had more proliferative and epithelial phenotypes than did subtype C. Tumors in subtype B showed a low frequency of overall kinase mutation, compared with subtype A or C.
Dr. Tabernero’s gene expression research follows previous work by others who successfully used gene expression patterns in breast cancer to create molecular subtypes that have been associated with prognosis and used to help create treatment plans. In colorectal cancer, previously only KRAS gene status has been shown to be a predictor of response to treatment focusing on epidermal growth factor receptor activity in advanced disease, he added.
A separate study is underway to validate the molecular subtype classification system in patients with stage IV colorectal cancer.
Dr. Kenneth H. Yu and his associates reported preliminary results of an ongoing, separate study that suggests pharmacogenomic profiling of 20 patients with nonresectable pancreatic adenocarcinomas predicted who would, or would not, respond to first-line chemotherapy.
The study so far has enrolled 50 patients with stage II-IV pancreatic adenocarcinoma who get blood samples taken before starting 1 of 12 different drug combinations chosen by their physician for first-line chemotherapy. If the tumor progresses on first-line treatment, another blood sample is taken before starting second-line chemotherapy. The blood is analyzed for pharmacogenomic characteristics in circulating tumor cells and invasive cells that might predict response or resistance to treatment.
The scientists analyzing the blood samples are blinded to treatment choices, and the treating physicians are blinded to the pharmacogenomic profile results of the blood samples, noted Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
Twenty patients so far have had the two blood samples. Using a pharmacogenomic model created in laboratory work by CellPath Therapeutics, the investigators predicted that tumors in six patients would be sensitive to the first-line treatment received, six other patients in an intermediate group were predicted to have some response to the first-line treatment, and tumors in eight patients were predicted to be resistant to the first-line treatments received.
The median time to tumor progression supported these classifications – 7.3 months in the sensitive group, 5.3 months in the intermediate group, and 3.7 months in the resistant group, Dr. Yu reported.
Analyses of gene pathways seem to have identified other predictors of treatment response. "Genes do not exist in isolation. The proteins these genes encode interact with each other in pathways – you can think of them as networks of genes and gene products. Changes in one gene along the pathway can affect other genes," he said in a separate press briefing.
A longer response to treatment was seen in patients with disruptions in the pathway called E2F1, which is known for regulating cell division. A shorter response to treatment was seen in patients who had disruptions in the NFkB pathway, which has been implicated in regulating cell division and cell survival, particularly in cancer. The investigators also found disruptions in the phospholipase C and retinoblastoma 1 pathways when tumors became resistant to treatment.
"Pharmacogenetic profiling is a promising and exploratory tool for predicting treatment response in pancreatic cancer," Dr. Yu said. The validation study continues, and future validation studies are planned.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
One of Dr. Yu’s coinvestigators works for CellPath Therapeutics and owns stock in the company, and another coinvestigator owns stock and is a consultant to CellPath. Dr. Tabernero has received funding from Agendia. Some of his associates in the study work for Agendia and/or own stock in the company, including the lead author, Iris Simon, Ph.D.
These two studies "highlight the direction that the field of oncology is going, both in terms of research and practice. The notion being that tumors that look the same under the microscope – colon cancers, for example – at the level of their molecular makeup may actually fit into several different categories that all look the same to a pathologist. We’re starting to use these categorizations based on the genetic makeup, the profile, and of what genes are turned on and off to help us make treatment decisions about which drugs might work best against which particular tumors, and which drugs might not work at all," Dr. Neal J. Meropol said.
The studies look at different ways of profiling tumors and tumor cells that ultimately could help guide treatment by predicting which tumors will respond to chemotherapy and which are likely to develop resistance.
Dr. Yu’s study of pharmacogenetic modeling "shows that it’s possible using a noninvasive methodology – simply a blood sample – to identify tumor cells and to characterize them at the molecular level. This is important, first of all, because it doesn’t require another biopsy of a patient’s tumor, which would be more invasive," Dr. Meropol said. "But, also, we know that when a tumor that initially responds to treatment starts to grow again, it has acquired new mutations, new characteristics that make it resistant to the therapy that it once responded to. This new technique allows you to sample the tumor over time through the bloodstream and change therapy appropriately based on changes in the tumor genomics at that point in time."
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
These two studies "highlight the direction that the field of oncology is going, both in terms of research and practice. The notion being that tumors that look the same under the microscope – colon cancers, for example – at the level of their molecular makeup may actually fit into several different categories that all look the same to a pathologist. We’re starting to use these categorizations based on the genetic makeup, the profile, and of what genes are turned on and off to help us make treatment decisions about which drugs might work best against which particular tumors, and which drugs might not work at all," Dr. Neal J. Meropol said.
The studies look at different ways of profiling tumors and tumor cells that ultimately could help guide treatment by predicting which tumors will respond to chemotherapy and which are likely to develop resistance.
Dr. Yu’s study of pharmacogenetic modeling "shows that it’s possible using a noninvasive methodology – simply a blood sample – to identify tumor cells and to characterize them at the molecular level. This is important, first of all, because it doesn’t require another biopsy of a patient’s tumor, which would be more invasive," Dr. Meropol said. "But, also, we know that when a tumor that initially responds to treatment starts to grow again, it has acquired new mutations, new characteristics that make it resistant to the therapy that it once responded to. This new technique allows you to sample the tumor over time through the bloodstream and change therapy appropriately based on changes in the tumor genomics at that point in time."
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
These two studies "highlight the direction that the field of oncology is going, both in terms of research and practice. The notion being that tumors that look the same under the microscope – colon cancers, for example – at the level of their molecular makeup may actually fit into several different categories that all look the same to a pathologist. We’re starting to use these categorizations based on the genetic makeup, the profile, and of what genes are turned on and off to help us make treatment decisions about which drugs might work best against which particular tumors, and which drugs might not work at all," Dr. Neal J. Meropol said.
The studies look at different ways of profiling tumors and tumor cells that ultimately could help guide treatment by predicting which tumors will respond to chemotherapy and which are likely to develop resistance.
Dr. Yu’s study of pharmacogenetic modeling "shows that it’s possible using a noninvasive methodology – simply a blood sample – to identify tumor cells and to characterize them at the molecular level. This is important, first of all, because it doesn’t require another biopsy of a patient’s tumor, which would be more invasive," Dr. Meropol said. "But, also, we know that when a tumor that initially responds to treatment starts to grow again, it has acquired new mutations, new characteristics that make it resistant to the therapy that it once responded to. This new technique allows you to sample the tumor over time through the bloodstream and change therapy appropriately based on changes in the tumor genomics at that point in time."
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
SAN FRANCISCO – Gene expression profiling of patients with colorectal cancer and pharmacogenomic modeling of patients with pancreatic cancer could help identify which patients will respond to particular chemotherapies, preliminary evidence from two small studies suggests.
Spanish investigators developed a molecular classification system using gene expression data from 188 patients with colorectal cancer to identify three subtypes of the cancer, which they called subtypes A, B and C. They then performed a multicenter validation study using tumor samples from 543 patients with stage II and III colorectal cancer, and classified 35% of samples as subtype A, 50% as subtype B, and 15% as subtype C.
They found that the different subtypes were associated with different clinical and biological characteristics and helped predict response to adjuvant chemotherapy regimens based on 5-fluorouracil (5-FU) when compared with 10 years of patient records, Dr. Josep Tabernero and his associates reported at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium.
Patients with subtype C colorectal cancer had a mesenchymal gene expression phenotype and did not respond to 5-FU–based chemotherapy, suggesting that new, targeted treatments need to be found for these tumors, said Dr. Tabernero, director of clinical research at Vall d’Hebron Institute of Oncology, Barcelona.
Patients with subtype A colorectal cancer had the best prognosis – "some of them don’t even need adjuvant therapy," he said in a separate press briefing – and did respond to 5-FU–based chemotherapy. Patients with subtype B had a poor prognosis but showed an even more dramatic response to adjuvant chemotherapy.
Subtypes A and B had more proliferative and epithelial phenotypes than did subtype C. Tumors in subtype B showed a low frequency of overall kinase mutation, compared with subtype A or C.
Dr. Tabernero’s gene expression research follows previous work by others who successfully used gene expression patterns in breast cancer to create molecular subtypes that have been associated with prognosis and used to help create treatment plans. In colorectal cancer, previously only KRAS gene status has been shown to be a predictor of response to treatment focusing on epidermal growth factor receptor activity in advanced disease, he added.
A separate study is underway to validate the molecular subtype classification system in patients with stage IV colorectal cancer.
Dr. Kenneth H. Yu and his associates reported preliminary results of an ongoing, separate study that suggests pharmacogenomic profiling of 20 patients with nonresectable pancreatic adenocarcinomas predicted who would, or would not, respond to first-line chemotherapy.
The study so far has enrolled 50 patients with stage II-IV pancreatic adenocarcinoma who get blood samples taken before starting 1 of 12 different drug combinations chosen by their physician for first-line chemotherapy. If the tumor progresses on first-line treatment, another blood sample is taken before starting second-line chemotherapy. The blood is analyzed for pharmacogenomic characteristics in circulating tumor cells and invasive cells that might predict response or resistance to treatment.
The scientists analyzing the blood samples are blinded to treatment choices, and the treating physicians are blinded to the pharmacogenomic profile results of the blood samples, noted Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
Twenty patients so far have had the two blood samples. Using a pharmacogenomic model created in laboratory work by CellPath Therapeutics, the investigators predicted that tumors in six patients would be sensitive to the first-line treatment received, six other patients in an intermediate group were predicted to have some response to the first-line treatment, and tumors in eight patients were predicted to be resistant to the first-line treatments received.
The median time to tumor progression supported these classifications – 7.3 months in the sensitive group, 5.3 months in the intermediate group, and 3.7 months in the resistant group, Dr. Yu reported.
Analyses of gene pathways seem to have identified other predictors of treatment response. "Genes do not exist in isolation. The proteins these genes encode interact with each other in pathways – you can think of them as networks of genes and gene products. Changes in one gene along the pathway can affect other genes," he said in a separate press briefing.
A longer response to treatment was seen in patients with disruptions in the pathway called E2F1, which is known for regulating cell division. A shorter response to treatment was seen in patients who had disruptions in the NFkB pathway, which has been implicated in regulating cell division and cell survival, particularly in cancer. The investigators also found disruptions in the phospholipase C and retinoblastoma 1 pathways when tumors became resistant to treatment.
"Pharmacogenetic profiling is a promising and exploratory tool for predicting treatment response in pancreatic cancer," Dr. Yu said. The validation study continues, and future validation studies are planned.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
One of Dr. Yu’s coinvestigators works for CellPath Therapeutics and owns stock in the company, and another coinvestigator owns stock and is a consultant to CellPath. Dr. Tabernero has received funding from Agendia. Some of his associates in the study work for Agendia and/or own stock in the company, including the lead author, Iris Simon, Ph.D.
SAN FRANCISCO – Gene expression profiling of patients with colorectal cancer and pharmacogenomic modeling of patients with pancreatic cancer could help identify which patients will respond to particular chemotherapies, preliminary evidence from two small studies suggests.
Spanish investigators developed a molecular classification system using gene expression data from 188 patients with colorectal cancer to identify three subtypes of the cancer, which they called subtypes A, B and C. They then performed a multicenter validation study using tumor samples from 543 patients with stage II and III colorectal cancer, and classified 35% of samples as subtype A, 50% as subtype B, and 15% as subtype C.
They found that the different subtypes were associated with different clinical and biological characteristics and helped predict response to adjuvant chemotherapy regimens based on 5-fluorouracil (5-FU) when compared with 10 years of patient records, Dr. Josep Tabernero and his associates reported at the American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium.
Patients with subtype C colorectal cancer had a mesenchymal gene expression phenotype and did not respond to 5-FU–based chemotherapy, suggesting that new, targeted treatments need to be found for these tumors, said Dr. Tabernero, director of clinical research at Vall d’Hebron Institute of Oncology, Barcelona.
Patients with subtype A colorectal cancer had the best prognosis – "some of them don’t even need adjuvant therapy," he said in a separate press briefing – and did respond to 5-FU–based chemotherapy. Patients with subtype B had a poor prognosis but showed an even more dramatic response to adjuvant chemotherapy.
Subtypes A and B had more proliferative and epithelial phenotypes than did subtype C. Tumors in subtype B showed a low frequency of overall kinase mutation, compared with subtype A or C.
Dr. Tabernero’s gene expression research follows previous work by others who successfully used gene expression patterns in breast cancer to create molecular subtypes that have been associated with prognosis and used to help create treatment plans. In colorectal cancer, previously only KRAS gene status has been shown to be a predictor of response to treatment focusing on epidermal growth factor receptor activity in advanced disease, he added.
A separate study is underway to validate the molecular subtype classification system in patients with stage IV colorectal cancer.
Dr. Kenneth H. Yu and his associates reported preliminary results of an ongoing, separate study that suggests pharmacogenomic profiling of 20 patients with nonresectable pancreatic adenocarcinomas predicted who would, or would not, respond to first-line chemotherapy.
The study so far has enrolled 50 patients with stage II-IV pancreatic adenocarcinoma who get blood samples taken before starting 1 of 12 different drug combinations chosen by their physician for first-line chemotherapy. If the tumor progresses on first-line treatment, another blood sample is taken before starting second-line chemotherapy. The blood is analyzed for pharmacogenomic characteristics in circulating tumor cells and invasive cells that might predict response or resistance to treatment.
The scientists analyzing the blood samples are blinded to treatment choices, and the treating physicians are blinded to the pharmacogenomic profile results of the blood samples, noted Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
Twenty patients so far have had the two blood samples. Using a pharmacogenomic model created in laboratory work by CellPath Therapeutics, the investigators predicted that tumors in six patients would be sensitive to the first-line treatment received, six other patients in an intermediate group were predicted to have some response to the first-line treatment, and tumors in eight patients were predicted to be resistant to the first-line treatments received.
The median time to tumor progression supported these classifications – 7.3 months in the sensitive group, 5.3 months in the intermediate group, and 3.7 months in the resistant group, Dr. Yu reported.
Analyses of gene pathways seem to have identified other predictors of treatment response. "Genes do not exist in isolation. The proteins these genes encode interact with each other in pathways – you can think of them as networks of genes and gene products. Changes in one gene along the pathway can affect other genes," he said in a separate press briefing.
A longer response to treatment was seen in patients with disruptions in the pathway called E2F1, which is known for regulating cell division. A shorter response to treatment was seen in patients who had disruptions in the NFkB pathway, which has been implicated in regulating cell division and cell survival, particularly in cancer. The investigators also found disruptions in the phospholipase C and retinoblastoma 1 pathways when tumors became resistant to treatment.
"Pharmacogenetic profiling is a promising and exploratory tool for predicting treatment response in pancreatic cancer," Dr. Yu said. The validation study continues, and future validation studies are planned.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
One of Dr. Yu’s coinvestigators works for CellPath Therapeutics and owns stock in the company, and another coinvestigator owns stock and is a consultant to CellPath. Dr. Tabernero has received funding from Agendia. Some of his associates in the study work for Agendia and/or own stock in the company, including the lead author, Iris Simon, Ph.D.
AT ASCO'S GASTROINTESTINAL CANCERS SYMPOSIUM
Major finding: Gene expression patterns identified three subtypes of stage II or III colorectal cancer with different responses to 5-FU–based adjuvant chemotherapy. Pharmacogenomic profiling predicted which patients with pancreatic cancer would respond to, have intermediate sensitivity, or fail first-line chemotherapy.
Data source: Prospective validation of colorectal cancer subtyping and treatment response in gene expression analysis of tumors in 385 patients, compared with records on 10 years of follow-up, and preliminary results of pharmacogenomic profiling in 20 of 50 patients with unresectable pancreatic adenocarcinoma.
Disclosures: One of Dr. Yu’s coinvestigators works for CellPath Therapeutics and owns stock in the company, and another coinvestigator owns stock and is a consultant to CellPath. Dr. Tabernero has received funding from Agendia. Some of his associates in the study work for Agendia and/or own stock in the company, including the lead author, Iris Simon, Ph.D.
Japanese study: S-1 adjuvant chemo improved pancreatic cancer survival
SAN FRANCISCO – Japanese patients who underwent surgery for pancreatic cancer were 44% less likely to die within 2 years if they were treated postoperatively with the chemotherapy drug S-1, compared with those given gemcitabine, an interim analysis of an ongoing phase III clinical trial found.
S-1 is not approved in the United States but is used in Japan to treat pancreatic cancer and several other cancers. A separate phase III clinical trial in the United States is underway to study S-1 in the treatment of stomach cancer, several oncology experts said in a press briefing held by the American Society of Clinical Oncology (ASCO).
The current Japanese study randomized 385 patients with pancreatic cancer to postoperative adjuvant therapy with S-1 or gemcitabine. A preplanned interim analysis conducted after the first 205 deaths found that 70% of the 187 patients on S-1 were alive at 2 years, compared with 53% of the 191 patients on gemcitabine, Dr. Katsuhiko Uesaka and his associates reported at a meeting on gastrointestinal cancers.
Patients in the S-1 group also were less likely to relapse. At 2 years, 49% on S-1 were free of disease progression, compared with 29% on gemcitabine, said Dr. Uesaka, medical deputy director of the Shizuoka (Japan) Cancer Center Hospital. The median time to disease progression was 23 months on S-1 and 11 months on gemcitabine.
The study is ongoing; a final analysis is planned after 240 deaths.
S-1 is an oral fluoropyrimidine that combines tegafur, gimeracil, and oteracil. It is approved in Europe for the treatment of gastric cancer at a lower dose than is used in Japan because the drug causes higher rates of diarrhea in white patients. "If the dose and schedule are optimized or adjusted, I expect that S-1 may be applicable for Caucasian patients with pancreatic cancer," he said. "I also expect that some kind of clinical study with S-1 will be done among Caucasian patients with pancreatic cancer."
Patients in the Japanese study tolerated S-1 relatively well, with rates of grade 3 or 4 adverse events below 5% for all except grade 3 hemoglobin toxicity, which affected 9% in the S-1 group. Rates of hematologic adverse events such as leukocytopenia or thrombocytopenia were lower with S-1, compared with gemcitabine, but the S-1 group had slightly higher rates of GI side effects such as stomatitis or diarrhea, he said.
Twenty-eight percent of patients in the S-1 group and 42% in the gemcitabine discontinued treatment, mainly because of toxicity or cancer recurrence, Dr. Uesaka said.
Dr. Philip A. Philip, who discussed Dr. Uesaka’s study at the meeting, said it’s likely that S-1 will become the standard of care for pancreatic cancer treatment in Japan. "In my opinion, non-Japanese studies must be considered to define the role of S-1" in non-Japanese populations, said Dr. Philip, leader of the gastrointestinal cancer multidisciplinary team and professor of medicine and oncology at Wayne State University, Detroit.
Studies should examine the feasibility of using a lower dose of S-1 in non-Japanese populations, he suggested, and explore S-1 treatment for early- and late-stage pancreatic cancer, use of the drug with other cancer drugs or drug combinations, and potential biomarkers that might identify which patients will respond best to S-1.
In a press briefing before the meeting, Dr. Kenneth H. Yu called the results from Dr. Uesaka’s study "very impressive." The findings "will lead to a lot more discussion about whether or not S-1 can be developed for use in the U.S. population," said Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies. Dr. Philip disclosed financial relationships with multiple pharmaceutical companies, though not with Taiho.
On Twitter @SherryBoschert
To put this into perspective, pancreatic cancer worldwide remains a highly lethal disease, yet about a third of patients who present with pancreatic cancer can undergo surgery with potentially curative intent. Among these patients, we’ve viewed gemcitabine as the standard adjuvant therapy to improve survival over surgery alone. For the first time, we now have another option that appears superior to gemcitabine in this setting, improving the cure rate for patients with pancreatic cancer that is resectable.
 |
|
S-1 is an oral formulation that contains three different components. One component, tegafur, is turned into 5-fluorouracil (5-FU) in the bloodstream. 5-FU is a commonly used drug in pancreatic cancer and other types of cancers worldwide. The other components of S-1 are added to improve the effectiveness of the tegafur and to reduce its side effects.
Oral capecitabine, which is available in the United States for a variety of cancers, also gets turned into 5-FU in the bloodstream. S-1 is similar, but with these other ingredients. S-1 is licensed in other countries and is in clinical development with the potential for future licensing in the United States. There’s a question of dosing and how the side effects profile might differ in different populations.
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
Dr. Philip A. Philip,
To put this into perspective, pancreatic cancer worldwide remains a highly lethal disease, yet about a third of patients who present with pancreatic cancer can undergo surgery with potentially curative intent. Among these patients, we’ve viewed gemcitabine as the standard adjuvant therapy to improve survival over surgery alone. For the first time, we now have another option that appears superior to gemcitabine in this setting, improving the cure rate for patients with pancreatic cancer that is resectable.
|
|
S-1 is an oral formulation that contains three different components. One component, tegafur, is turned into 5-fluorouracil (5-FU) in the bloodstream. 5-FU is a commonly used drug in pancreatic cancer and other types of cancers worldwide. The other components of S-1 are added to improve the effectiveness of the tegafur and to reduce its side effects.
Oral capecitabine, which is available in the United States for a variety of cancers, also gets turned into 5-FU in the bloodstream. S-1 is similar, but with these other ingredients. S-1 is licensed in other countries and is in clinical development with the potential for future licensing in the United States. There’s a question of dosing and how the side effects profile might differ in different populations.
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
To put this into perspective, pancreatic cancer worldwide remains a highly lethal disease, yet about a third of patients who present with pancreatic cancer can undergo surgery with potentially curative intent. Among these patients, we’ve viewed gemcitabine as the standard adjuvant therapy to improve survival over surgery alone. For the first time, we now have another option that appears superior to gemcitabine in this setting, improving the cure rate for patients with pancreatic cancer that is resectable.
|
|
S-1 is an oral formulation that contains three different components. One component, tegafur, is turned into 5-fluorouracil (5-FU) in the bloodstream. 5-FU is a commonly used drug in pancreatic cancer and other types of cancers worldwide. The other components of S-1 are added to improve the effectiveness of the tegafur and to reduce its side effects.
Oral capecitabine, which is available in the United States for a variety of cancers, also gets turned into 5-FU in the bloodstream. S-1 is similar, but with these other ingredients. S-1 is licensed in other countries and is in clinical development with the potential for future licensing in the United States. There’s a question of dosing and how the side effects profile might differ in different populations.
Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.
SAN FRANCISCO – Japanese patients who underwent surgery for pancreatic cancer were 44% less likely to die within 2 years if they were treated postoperatively with the chemotherapy drug S-1, compared with those given gemcitabine, an interim analysis of an ongoing phase III clinical trial found.
S-1 is not approved in the United States but is used in Japan to treat pancreatic cancer and several other cancers. A separate phase III clinical trial in the United States is underway to study S-1 in the treatment of stomach cancer, several oncology experts said in a press briefing held by the American Society of Clinical Oncology (ASCO).
The current Japanese study randomized 385 patients with pancreatic cancer to postoperative adjuvant therapy with S-1 or gemcitabine. A preplanned interim analysis conducted after the first 205 deaths found that 70% of the 187 patients on S-1 were alive at 2 years, compared with 53% of the 191 patients on gemcitabine, Dr. Katsuhiko Uesaka and his associates reported at a meeting on gastrointestinal cancers.
Patients in the S-1 group also were less likely to relapse. At 2 years, 49% on S-1 were free of disease progression, compared with 29% on gemcitabine, said Dr. Uesaka, medical deputy director of the Shizuoka (Japan) Cancer Center Hospital. The median time to disease progression was 23 months on S-1 and 11 months on gemcitabine.
The study is ongoing; a final analysis is planned after 240 deaths.
S-1 is an oral fluoropyrimidine that combines tegafur, gimeracil, and oteracil. It is approved in Europe for the treatment of gastric cancer at a lower dose than is used in Japan because the drug causes higher rates of diarrhea in white patients. "If the dose and schedule are optimized or adjusted, I expect that S-1 may be applicable for Caucasian patients with pancreatic cancer," he said. "I also expect that some kind of clinical study with S-1 will be done among Caucasian patients with pancreatic cancer."
Patients in the Japanese study tolerated S-1 relatively well, with rates of grade 3 or 4 adverse events below 5% for all except grade 3 hemoglobin toxicity, which affected 9% in the S-1 group. Rates of hematologic adverse events such as leukocytopenia or thrombocytopenia were lower with S-1, compared with gemcitabine, but the S-1 group had slightly higher rates of GI side effects such as stomatitis or diarrhea, he said.
Twenty-eight percent of patients in the S-1 group and 42% in the gemcitabine discontinued treatment, mainly because of toxicity or cancer recurrence, Dr. Uesaka said.
Dr. Philip A. Philip, who discussed Dr. Uesaka’s study at the meeting, said it’s likely that S-1 will become the standard of care for pancreatic cancer treatment in Japan. "In my opinion, non-Japanese studies must be considered to define the role of S-1" in non-Japanese populations, said Dr. Philip, leader of the gastrointestinal cancer multidisciplinary team and professor of medicine and oncology at Wayne State University, Detroit.
Studies should examine the feasibility of using a lower dose of S-1 in non-Japanese populations, he suggested, and explore S-1 treatment for early- and late-stage pancreatic cancer, use of the drug with other cancer drugs or drug combinations, and potential biomarkers that might identify which patients will respond best to S-1.
In a press briefing before the meeting, Dr. Kenneth H. Yu called the results from Dr. Uesaka’s study "very impressive." The findings "will lead to a lot more discussion about whether or not S-1 can be developed for use in the U.S. population," said Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies. Dr. Philip disclosed financial relationships with multiple pharmaceutical companies, though not with Taiho.
On Twitter @SherryBoschert
SAN FRANCISCO – Japanese patients who underwent surgery for pancreatic cancer were 44% less likely to die within 2 years if they were treated postoperatively with the chemotherapy drug S-1, compared with those given gemcitabine, an interim analysis of an ongoing phase III clinical trial found.
S-1 is not approved in the United States but is used in Japan to treat pancreatic cancer and several other cancers. A separate phase III clinical trial in the United States is underway to study S-1 in the treatment of stomach cancer, several oncology experts said in a press briefing held by the American Society of Clinical Oncology (ASCO).
The current Japanese study randomized 385 patients with pancreatic cancer to postoperative adjuvant therapy with S-1 or gemcitabine. A preplanned interim analysis conducted after the first 205 deaths found that 70% of the 187 patients on S-1 were alive at 2 years, compared with 53% of the 191 patients on gemcitabine, Dr. Katsuhiko Uesaka and his associates reported at a meeting on gastrointestinal cancers.
Patients in the S-1 group also were less likely to relapse. At 2 years, 49% on S-1 were free of disease progression, compared with 29% on gemcitabine, said Dr. Uesaka, medical deputy director of the Shizuoka (Japan) Cancer Center Hospital. The median time to disease progression was 23 months on S-1 and 11 months on gemcitabine.
The study is ongoing; a final analysis is planned after 240 deaths.
S-1 is an oral fluoropyrimidine that combines tegafur, gimeracil, and oteracil. It is approved in Europe for the treatment of gastric cancer at a lower dose than is used in Japan because the drug causes higher rates of diarrhea in white patients. "If the dose and schedule are optimized or adjusted, I expect that S-1 may be applicable for Caucasian patients with pancreatic cancer," he said. "I also expect that some kind of clinical study with S-1 will be done among Caucasian patients with pancreatic cancer."
Patients in the Japanese study tolerated S-1 relatively well, with rates of grade 3 or 4 adverse events below 5% for all except grade 3 hemoglobin toxicity, which affected 9% in the S-1 group. Rates of hematologic adverse events such as leukocytopenia or thrombocytopenia were lower with S-1, compared with gemcitabine, but the S-1 group had slightly higher rates of GI side effects such as stomatitis or diarrhea, he said.
Twenty-eight percent of patients in the S-1 group and 42% in the gemcitabine discontinued treatment, mainly because of toxicity or cancer recurrence, Dr. Uesaka said.
Dr. Philip A. Philip, who discussed Dr. Uesaka’s study at the meeting, said it’s likely that S-1 will become the standard of care for pancreatic cancer treatment in Japan. "In my opinion, non-Japanese studies must be considered to define the role of S-1" in non-Japanese populations, said Dr. Philip, leader of the gastrointestinal cancer multidisciplinary team and professor of medicine and oncology at Wayne State University, Detroit.
Studies should examine the feasibility of using a lower dose of S-1 in non-Japanese populations, he suggested, and explore S-1 treatment for early- and late-stage pancreatic cancer, use of the drug with other cancer drugs or drug combinations, and potential biomarkers that might identify which patients will respond best to S-1.
In a press briefing before the meeting, Dr. Kenneth H. Yu called the results from Dr. Uesaka’s study "very impressive." The findings "will lead to a lot more discussion about whether or not S-1 can be developed for use in the U.S. population," said Dr. Yu of Memorial Sloan-Kettering Cancer Center, New York.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies. Dr. Philip disclosed financial relationships with multiple pharmaceutical companies, though not with Taiho.
On Twitter @SherryBoschert
Dr. Philip A. Philip,
Dr. Philip A. Philip,
AT A MEETING ON GASTROINTESTINAL CANCERS
Major Finding: 2-year survival rates for Japanese patients who underwent resection of pancreatic cancer were 70% for those receiving postoperative S-1 and 44% for patients receiving postoperative gemcitabine.
Data Source: A preplanned interim analysis of 205 patients in an ongoing randomized, phase III clinical trial of 385 patients.
Disclosures: Taiho Pharmaceutical Company, which makes S-1, funded the study. Dr. Uesaka has received honoraria from Taiho and Eli Lilly and Co. Some of his associates in the study have received honoraria or research funding from Taiho or other pharmaceutical companies.
Add-on nab-paclitaxel extends survival in metastatic pancreatic cancer
Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.
Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.
 |
|
Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.
In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.
The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.
If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.
What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.
Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.
Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.
Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.
This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.
Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.
|
|
Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.
In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.
The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.
If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.
What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.
Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.
Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.
Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.
This study showed a highly statistically significant difference in primary and secondary endpoints. It’s important that the benefit was across predefined patient subgroups.
Nab-paclitaxel plus gemcitabine is a new treatment option for patients with metastatic pancreatic cancer, along with gemcitabine with or without erlotinib, and FOLFIRINOX (combination therapy with folinic acid, fluorouracil, irinotecan, and oxaliplatin). The immediate question would be the relative roles of nab-paclitaxel versus FOLFIRINOX in our day-to-day practice and in our future clinical research activities. Related to this question is how to sequence these two regimens in a given patient.
|
|
Obviously, a head-to-head comparison will answer these questions, but I’m not sure if a study like that will happen, or will happen soon enough. Whenever it happens, we will have to wait several years before we get an answer.
In my informal comparison of data on tolerability in this study and previous data from a multicenter, randomized trial of FOLFIRINOX versus gemcitabine, it seems that comparisons of selected side effects that would most impact quality of life in our patients may not be as simple as we’d like them to be (N. Engl. J. Med. 2011;364:1817-25).FOLFIRINOX causes more fatigue (in 24% vs. 17%) and diarrhea (in 13% vs. 6%), but there’s more neuropathy with patients who got nab-paclitaxel (in 17% vs. 9%). Keep in mind that the nature of the neuropathy is different with the two agents, especially with regard to reversibility.
The proportion of patients who were taken off the study or refused the study drug in the MPACT trial was not reported.
If we look at efficacy parameters, we see differences that may favor FOLFIRINOX (median overall survival, 11.1 months vs. 8.7 months). That leads to the question of whether there were any differences in the two populations. Here again, when we try to compare the two populations, we see some randomness between the two. One difference is that MPACT accrued patients from different parts of the world, with more than 50% from the United States. Pivotal trial data on FOLFIRINOX came from fewer centers in a single country, France.
What can we conclude? MPACT is the fourth positive clinical trial in advanced pancreatic cancer in more than four decades. We have to do much better. This study is an example of developing a drug from preclinical trial to pilot study to phase III trial, and the investigators have to be congratulated for that.
Nab-paclitaxel plus gemcitabine is a new standard regimen in patients with metastatic pancreatic cancer who have a favorable performance status. It represents an incremental benefit in this patient population. Nab-paclitaxel alone, with gemcitabine, or in combination with other agents, must be considered for further development in earlier-stage disease as well as possibly a platform for adding biologicals.
Finally, an important point: The rationale for developing nab-paclitaxel in pancreatic cancer was based on hypotheses largely related to targeting the stroma. I strongly urge the investigators to grab this opportunity and go back to the lab to determine the molecular basis of this clinical benefit and its association with any biomarkers.
Dr. Philip A. Philip is leader of the Gastrointestinal Cancer Multidisciplinary Team and a professor of medicine and oncology at Wayne State University, Detroit. He presented these comments after Dr. Von Hoff’s talk at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies, though not with Celgene.
Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
Median overall survival in 861 patients with metastatic pancreatic cancer increased from 6.7 months in those randomized to gemcitabine therapy to 8.5 months in patients receiving gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel).
The international phase III clinical trial, known as MPACT, also showed significantly improved long-term survival rates in patients on the combination compared with gemcitabine alone – 35% versus 22% at 1 year and 9% versus 4% at 2 years, Dr. Daniel D. Von Hoff and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The findings suggest that first-line therapy with nab-paclitaxel (Abraxane) plus gemcitabine "could become the backbone of new regimens" for metastatic pancreatic cancer, said Dr. Von Hoff, chief scientific officer at Scottsdale (Ariz.) Healthcare’s Clinical Research Institute and at TGen (the Translational Genomics Research Institute), Phoenix.
The study randomized patients with metastatic cancer and a Karnofsky Performance Status score of at least 70 to treatment with either gemcitabine (a first cycle of 1,000 mg/m2 weekly for 7 weeks, then a second cycle on days 1, 8, and 15 every 4 weeks), or the combination (nab-paclitaxel 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks). Both therapies were delivered intravenously.
The improved survival on combination therapy began appearing after 2-3 months of treatment and continued to separate from the monotherapy group over time, said Dr. Von Hoff, who also is a professor of medicine at the University of Arizona, Phoenix.
The time to disease progression (progression-free survival) increased from 3.7 months on gemcitabine alone to 5.5 months on nab-paclitaxel plus gemcitabine, independent reviews in preplanned sensitivity analyses found. Seven percent of patients on gemcitabine alone and 23% of patients on the combination showed an objective response to treatment, independent reviewers also reported.
The benefits extended across all patient subgroups, according to analyses of prespecified subgroups.
The most common adverse events rated grade 3 or higher included neutropenia (38% in the combination group versus 27% on gemcitabine alone), fatigue (17% versus 7%), and peripheral neuropathy (17% versus 1%). The neuropathy improved to grade 1 or lower in a median of 29 days, he reported. Three percent of the combination group and 1% of the gemcitabine group developed febrile neutropenia. Growth factors were given to 26% in the combination group and 15% on monotherapy. The proportion of patients with at least one adverse event leading to death was 4% in each group.
Baseline characteristics were well balanced in the patient groups, who were enrolled at 151 sites in 11 countries. The median age was 63 years. The cohort came from community and academic centers and represented "typical patients" seen in oncology practices, Dr. Von Hoff said.
Positive results from in vitro studies and a phase I/II clinical trial preceded the MPACT study.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
FROM A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Median overall survival in patients with metastatic pancreatic cancer increased from 6.7 months on gemcitabine to 8.5 months on nab-paclitaxel plus gemcitabine.
Data Source: International phase III clinical trial of first-line therapy in 861 patients.
Disclosures: Celgene, which markets Abraxane, funded the study. Dr. Von Hoff and most of his associates in the study reported having financial relationships with Celgene.
Statins may reduce mortality in hepatocellular cancer
The use of statins may reduce the risk of death in patients with hepatocellular cancer by 30%, a retrospective study of 639 patients suggests.
Median overall survival from 2000 until 2011 was 22 months for the 68 statin users, significantly longer than the 18-month median survival for the 571 non-statin users, Dr. Young Kwang Chae and his associates reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO). The study won a Merit Award at the meeting.
The 30% improvement in survival with statin use also was seen in subgroups of patients who received systemic or local therapy. The benefits were still seen after controlling for the effects of age, sex, race, cancer staging, liver cirrhosis, cancer treatment, alcohol use, diabetes, and hepatitis C or hepatitis B infection.
The findings warrant a large prospective study to validate the results, said Dr. Chae, a fellow at the University of Texas M.D. Anderson Cancer Center, Houston.
Some preclinical evidence supports the idea that statins may have antitumor activity, and several observational studies have reported inverse associations between statin use and the incidence of hepatocellular cancer.
In the current study – the largest so far to look at the effects of statins on hepatocellular cancer outcomes – median survival for all 639 patients with hepatocellular cancer was 19 months. Approximately 11% of patients reported statin use.
Statin users were significantly less likely to have underlying liver cirrhosis (48%) compared with non-statin users (64%). Only patients free of cirrhosis showed a significant, 30% decrease in mortality with statin use. The survival benefit of statins was not seen in patients with cirrhosis.
Among patients without cirrhosis, the median survival was 32 months for statin users and 22 months for non-statin users. Among patients with cirrhosis, the median survival was 18 months for statin users and 19 months for non-statin users.
There were some other significant differences between statin users and nonusers. Statin users were more likely to be aged 50 years or older (97%) compared with nonusers (86%), and more likely to have diabetes (52% and 32%, respectively).
Patients not using statins were more likely to have a history of hepatitis C or B infection (50%) compared with statin users (29%). A history of hepatitis, however, did not affect the association between statin use and improved mortality, Dr. Chae reported.
Fifty-three percent of patients in each group were treated with chemotherapy for the hepatocellular cancer. Statin users were more likely to undergo surgery (24%) or to receive local treatment (28%) compared with non-statin users, 18% of whom had surgery and 15% of whom had local treatment. The remaining option – no treatment – was more likely in non-statin users than in patients on statins (15% vs. 9%, respectively). Patients could receive more than one category of treatment.
Patients had a mean age of 63 years; 73% were male, and 66% were white. Seventy-one percent of the hepatocellular cancers were diagnosed at tumor stage III or IV.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Chae reported having no financial disclosures.
On Twitter @sherryboschert
The use of statins may reduce the risk of death in patients with hepatocellular cancer by 30%, a retrospective study of 639 patients suggests.
Median overall survival from 2000 until 2011 was 22 months for the 68 statin users, significantly longer than the 18-month median survival for the 571 non-statin users, Dr. Young Kwang Chae and his associates reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO). The study won a Merit Award at the meeting.
The 30% improvement in survival with statin use also was seen in subgroups of patients who received systemic or local therapy. The benefits were still seen after controlling for the effects of age, sex, race, cancer staging, liver cirrhosis, cancer treatment, alcohol use, diabetes, and hepatitis C or hepatitis B infection.
The findings warrant a large prospective study to validate the results, said Dr. Chae, a fellow at the University of Texas M.D. Anderson Cancer Center, Houston.
Some preclinical evidence supports the idea that statins may have antitumor activity, and several observational studies have reported inverse associations between statin use and the incidence of hepatocellular cancer.
In the current study – the largest so far to look at the effects of statins on hepatocellular cancer outcomes – median survival for all 639 patients with hepatocellular cancer was 19 months. Approximately 11% of patients reported statin use.
Statin users were significantly less likely to have underlying liver cirrhosis (48%) compared with non-statin users (64%). Only patients free of cirrhosis showed a significant, 30% decrease in mortality with statin use. The survival benefit of statins was not seen in patients with cirrhosis.
Among patients without cirrhosis, the median survival was 32 months for statin users and 22 months for non-statin users. Among patients with cirrhosis, the median survival was 18 months for statin users and 19 months for non-statin users.
There were some other significant differences between statin users and nonusers. Statin users were more likely to be aged 50 years or older (97%) compared with nonusers (86%), and more likely to have diabetes (52% and 32%, respectively).
Patients not using statins were more likely to have a history of hepatitis C or B infection (50%) compared with statin users (29%). A history of hepatitis, however, did not affect the association between statin use and improved mortality, Dr. Chae reported.
Fifty-three percent of patients in each group were treated with chemotherapy for the hepatocellular cancer. Statin users were more likely to undergo surgery (24%) or to receive local treatment (28%) compared with non-statin users, 18% of whom had surgery and 15% of whom had local treatment. The remaining option – no treatment – was more likely in non-statin users than in patients on statins (15% vs. 9%, respectively). Patients could receive more than one category of treatment.
Patients had a mean age of 63 years; 73% were male, and 66% were white. Seventy-one percent of the hepatocellular cancers were diagnosed at tumor stage III or IV.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Chae reported having no financial disclosures.
On Twitter @sherryboschert
The use of statins may reduce the risk of death in patients with hepatocellular cancer by 30%, a retrospective study of 639 patients suggests.
Median overall survival from 2000 until 2011 was 22 months for the 68 statin users, significantly longer than the 18-month median survival for the 571 non-statin users, Dr. Young Kwang Chae and his associates reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO). The study won a Merit Award at the meeting.
The 30% improvement in survival with statin use also was seen in subgroups of patients who received systemic or local therapy. The benefits were still seen after controlling for the effects of age, sex, race, cancer staging, liver cirrhosis, cancer treatment, alcohol use, diabetes, and hepatitis C or hepatitis B infection.
The findings warrant a large prospective study to validate the results, said Dr. Chae, a fellow at the University of Texas M.D. Anderson Cancer Center, Houston.
Some preclinical evidence supports the idea that statins may have antitumor activity, and several observational studies have reported inverse associations between statin use and the incidence of hepatocellular cancer.
In the current study – the largest so far to look at the effects of statins on hepatocellular cancer outcomes – median survival for all 639 patients with hepatocellular cancer was 19 months. Approximately 11% of patients reported statin use.
Statin users were significantly less likely to have underlying liver cirrhosis (48%) compared with non-statin users (64%). Only patients free of cirrhosis showed a significant, 30% decrease in mortality with statin use. The survival benefit of statins was not seen in patients with cirrhosis.
Among patients without cirrhosis, the median survival was 32 months for statin users and 22 months for non-statin users. Among patients with cirrhosis, the median survival was 18 months for statin users and 19 months for non-statin users.
There were some other significant differences between statin users and nonusers. Statin users were more likely to be aged 50 years or older (97%) compared with nonusers (86%), and more likely to have diabetes (52% and 32%, respectively).
Patients not using statins were more likely to have a history of hepatitis C or B infection (50%) compared with statin users (29%). A history of hepatitis, however, did not affect the association between statin use and improved mortality, Dr. Chae reported.
Fifty-three percent of patients in each group were treated with chemotherapy for the hepatocellular cancer. Statin users were more likely to undergo surgery (24%) or to receive local treatment (28%) compared with non-statin users, 18% of whom had surgery and 15% of whom had local treatment. The remaining option – no treatment – was more likely in non-statin users than in patients on statins (15% vs. 9%, respectively). Patients could receive more than one category of treatment.
Patients had a mean age of 63 years; 73% were male, and 66% were white. Seventy-one percent of the hepatocellular cancers were diagnosed at tumor stage III or IV.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Chae reported having no financial disclosures.
On Twitter @sherryboschert
FROM A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major finding: Patients with hepatocellular cancer showed significantly improved median survival if they were on statins (22 months) compared with non-statin users (18 months).
Data source: Retrospective study of 639 adults with hepatocellular cancer followed over an 11-year period from 2000 to 2011.
Disclosures: Dr. Chae reported having no financial disclosures.
