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Bevacizumab boosts capecitabine response in elderly with metastatic colorectal cancer
SAN FRANCISCO – Adding bevacizumab to capecitabine for first-line therapy for elderly patients with metastatic colorectal cancer significantly delayed disease progression and improved treatment response rates compared with capecitabine alone in a study of 280 patients.
The study is the first prospective, phase III clinical trial of a biologic agent (bevacizumab) for metastatic colorectal cancer in patients aged 70 years or older, who comprise many patients with this disease and generally are underrepresented in clinical trials, Dr. David Cunningham said.
Median progression-free survival rates were 5.1 months with capecitabine (Xeloda, Roche) and 9.1 months with capecitabine plus bevacizumab (Avastin, Roche/Genentech), an intent-to-treat analysis showed. Patients were followed for a median of 22 months in the monotherapy arm and 25 months in the combination therapy arm.
Among secondary outcomes, overall response rates were significantly better with the combination regimen (19%) compared with monotherapy (10%), he and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
The capecitabine/bevacizumab group also showed improved median overall survival (20.7 months) compared with the control group (16.8 months). This difference did not reach statistical significance, but the study was not powered to show a difference in overall survival. The primary outcome was progression-free survival, said Dr. Cunningham, head of the gastrointestinal unit at Royal Marsden Hospital, London.
The benefits were seen across all subgroups, he added.
The Avastin in the Elderly with Xeloda (AVEX) trial randomized elderly patients from 10 countries to first-line treatment with capecitabine 1,000 mg/m2 b.i.d. on days 1-4 with or without bevacizumab 7.5 mg/kg every 3 weeks. Patients had a median age of 76 years at enrollment and an Eastern Cooperative Oncology Group performance status of 0-2. The study recruited patients who were not considered optimal candidates for combination therapy including irinotecan or oxaliplatin. Baseline characteristics were similar between treatment groups.
Grade 3 or higher adverse events occurred in 59% of patients on the combination therapy, compared with 44% on capecitabine alone, a safety analysis on 270 patients found. Rates of any serious adverse events were 31% with combination therapy and 32% with monotherapy. Adverse events led to death in 8% of the combination group and 12% on monotherapy.
"As a clinician, I was impressed with how well tolerated this combination was," Dr. Cunningham said. No signals of unusual adverse events were seen in this older population.
Among grade 3 or higher adverse events of special interest with bevacizumab or related to chemotherapy, hypertension developed in 2.2% on the combination and 1.5% on monotherapy, venous thromboembolic events were seen in 8.2% on the combination and 4.4% on monotherapy, arterial thromboembolic events occurred in 3.7% on the combination and 1.5% on monotherapy, and proteinuria was seen in 1.5% on the combination and in no patients on monotherapy. Grade 3 or higher bleeding, pulmonary hemorrhage, or heart failure occurred in less than 1% on monotherapy and no patients on combination treatment.
Patients on the combination therapy were exposed to treatment for a longer duration (5.8 months) compared with those on monotherapy (4.2 months). The capecitabine-plus-bevacizumab group underwent a median of nine cycles of therapy compared with six cycles in the capecitabine group.
The combination treatment was "effective, generally well tolerated, and produced meaningful disease control and good survival," Dr. Cunningham said. Because the multicenter study included patients from around the world, "these results should be transferable" and generalizable to elderly patients with metastatic colorectal cancer, he added.
Thirty-seven percent of patients in each treatment group received subsequent therapy for metastatic colorectal cancer.
Bevacizumab is considered part of standard care for metastatic colorectal cancer in general, and prior studies had suggested that elderly patients would benefit from adding bevacizumab to chemotherapy, he said.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Cunningham reported receiving research funding from Roche, which markets capecitabine and bevacizumab, and from AstraZeneca and Merck KGaA. Several of his associates in the study were employees, leaders, or stockholders in Roche.
On Twitter @sherryboschert
SAN FRANCISCO – Adding bevacizumab to capecitabine for first-line therapy for elderly patients with metastatic colorectal cancer significantly delayed disease progression and improved treatment response rates compared with capecitabine alone in a study of 280 patients.
The study is the first prospective, phase III clinical trial of a biologic agent (bevacizumab) for metastatic colorectal cancer in patients aged 70 years or older, who comprise many patients with this disease and generally are underrepresented in clinical trials, Dr. David Cunningham said.
Median progression-free survival rates were 5.1 months with capecitabine (Xeloda, Roche) and 9.1 months with capecitabine plus bevacizumab (Avastin, Roche/Genentech), an intent-to-treat analysis showed. Patients were followed for a median of 22 months in the monotherapy arm and 25 months in the combination therapy arm.
Among secondary outcomes, overall response rates were significantly better with the combination regimen (19%) compared with monotherapy (10%), he and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
The capecitabine/bevacizumab group also showed improved median overall survival (20.7 months) compared with the control group (16.8 months). This difference did not reach statistical significance, but the study was not powered to show a difference in overall survival. The primary outcome was progression-free survival, said Dr. Cunningham, head of the gastrointestinal unit at Royal Marsden Hospital, London.
The benefits were seen across all subgroups, he added.
The Avastin in the Elderly with Xeloda (AVEX) trial randomized elderly patients from 10 countries to first-line treatment with capecitabine 1,000 mg/m2 b.i.d. on days 1-4 with or without bevacizumab 7.5 mg/kg every 3 weeks. Patients had a median age of 76 years at enrollment and an Eastern Cooperative Oncology Group performance status of 0-2. The study recruited patients who were not considered optimal candidates for combination therapy including irinotecan or oxaliplatin. Baseline characteristics were similar between treatment groups.
Grade 3 or higher adverse events occurred in 59% of patients on the combination therapy, compared with 44% on capecitabine alone, a safety analysis on 270 patients found. Rates of any serious adverse events were 31% with combination therapy and 32% with monotherapy. Adverse events led to death in 8% of the combination group and 12% on monotherapy.
"As a clinician, I was impressed with how well tolerated this combination was," Dr. Cunningham said. No signals of unusual adverse events were seen in this older population.
Among grade 3 or higher adverse events of special interest with bevacizumab or related to chemotherapy, hypertension developed in 2.2% on the combination and 1.5% on monotherapy, venous thromboembolic events were seen in 8.2% on the combination and 4.4% on monotherapy, arterial thromboembolic events occurred in 3.7% on the combination and 1.5% on monotherapy, and proteinuria was seen in 1.5% on the combination and in no patients on monotherapy. Grade 3 or higher bleeding, pulmonary hemorrhage, or heart failure occurred in less than 1% on monotherapy and no patients on combination treatment.
Patients on the combination therapy were exposed to treatment for a longer duration (5.8 months) compared with those on monotherapy (4.2 months). The capecitabine-plus-bevacizumab group underwent a median of nine cycles of therapy compared with six cycles in the capecitabine group.
The combination treatment was "effective, generally well tolerated, and produced meaningful disease control and good survival," Dr. Cunningham said. Because the multicenter study included patients from around the world, "these results should be transferable" and generalizable to elderly patients with metastatic colorectal cancer, he added.
Thirty-seven percent of patients in each treatment group received subsequent therapy for metastatic colorectal cancer.
Bevacizumab is considered part of standard care for metastatic colorectal cancer in general, and prior studies had suggested that elderly patients would benefit from adding bevacizumab to chemotherapy, he said.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Cunningham reported receiving research funding from Roche, which markets capecitabine and bevacizumab, and from AstraZeneca and Merck KGaA. Several of his associates in the study were employees, leaders, or stockholders in Roche.
On Twitter @sherryboschert
SAN FRANCISCO – Adding bevacizumab to capecitabine for first-line therapy for elderly patients with metastatic colorectal cancer significantly delayed disease progression and improved treatment response rates compared with capecitabine alone in a study of 280 patients.
The study is the first prospective, phase III clinical trial of a biologic agent (bevacizumab) for metastatic colorectal cancer in patients aged 70 years or older, who comprise many patients with this disease and generally are underrepresented in clinical trials, Dr. David Cunningham said.
Median progression-free survival rates were 5.1 months with capecitabine (Xeloda, Roche) and 9.1 months with capecitabine plus bevacizumab (Avastin, Roche/Genentech), an intent-to-treat analysis showed. Patients were followed for a median of 22 months in the monotherapy arm and 25 months in the combination therapy arm.
Among secondary outcomes, overall response rates were significantly better with the combination regimen (19%) compared with monotherapy (10%), he and his associates reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
The capecitabine/bevacizumab group also showed improved median overall survival (20.7 months) compared with the control group (16.8 months). This difference did not reach statistical significance, but the study was not powered to show a difference in overall survival. The primary outcome was progression-free survival, said Dr. Cunningham, head of the gastrointestinal unit at Royal Marsden Hospital, London.
The benefits were seen across all subgroups, he added.
The Avastin in the Elderly with Xeloda (AVEX) trial randomized elderly patients from 10 countries to first-line treatment with capecitabine 1,000 mg/m2 b.i.d. on days 1-4 with or without bevacizumab 7.5 mg/kg every 3 weeks. Patients had a median age of 76 years at enrollment and an Eastern Cooperative Oncology Group performance status of 0-2. The study recruited patients who were not considered optimal candidates for combination therapy including irinotecan or oxaliplatin. Baseline characteristics were similar between treatment groups.
Grade 3 or higher adverse events occurred in 59% of patients on the combination therapy, compared with 44% on capecitabine alone, a safety analysis on 270 patients found. Rates of any serious adverse events were 31% with combination therapy and 32% with monotherapy. Adverse events led to death in 8% of the combination group and 12% on monotherapy.
"As a clinician, I was impressed with how well tolerated this combination was," Dr. Cunningham said. No signals of unusual adverse events were seen in this older population.
Among grade 3 or higher adverse events of special interest with bevacizumab or related to chemotherapy, hypertension developed in 2.2% on the combination and 1.5% on monotherapy, venous thromboembolic events were seen in 8.2% on the combination and 4.4% on monotherapy, arterial thromboembolic events occurred in 3.7% on the combination and 1.5% on monotherapy, and proteinuria was seen in 1.5% on the combination and in no patients on monotherapy. Grade 3 or higher bleeding, pulmonary hemorrhage, or heart failure occurred in less than 1% on monotherapy and no patients on combination treatment.
Patients on the combination therapy were exposed to treatment for a longer duration (5.8 months) compared with those on monotherapy (4.2 months). The capecitabine-plus-bevacizumab group underwent a median of nine cycles of therapy compared with six cycles in the capecitabine group.
The combination treatment was "effective, generally well tolerated, and produced meaningful disease control and good survival," Dr. Cunningham said. Because the multicenter study included patients from around the world, "these results should be transferable" and generalizable to elderly patients with metastatic colorectal cancer, he added.
Thirty-seven percent of patients in each treatment group received subsequent therapy for metastatic colorectal cancer.
Bevacizumab is considered part of standard care for metastatic colorectal cancer in general, and prior studies had suggested that elderly patients would benefit from adding bevacizumab to chemotherapy, he said.
The meeting was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Cunningham reported receiving research funding from Roche, which markets capecitabine and bevacizumab, and from AstraZeneca and Merck KGaA. Several of his associates in the study were employees, leaders, or stockholders in Roche.
On Twitter @sherryboschert
FROM A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF ONCOLOGY
Major Finding: Progression-free survival improved from 5.1 months on capecitabine to 9.1 months on capecitabine plus bevacizumab in elderly patients with metastatic colorectal cancer, and overall response rates increased from 10% to 19%, respectively.
Data Source: International, randomized, controlled, open-label phase III clinical trial of 280 patients.
Disclosures: Dr. Cunningham reported receiving research funding from Roche, which markets capecitabine and bevacizumab, and from AstraZeneca and Merck KGaA. Several of his associates in the study were employees, leaders, or stockholders in Roche.
Adding cetuximab to chemoradiotherapy harmful in esophageal cancer
SAN FRANCISCO – A phase II/III clinical trial of adding cetuximab to chemoradiotherapy for localized esophageal cancer was stopped early when interim results showed greater toxicity, less completion of chemoradiotherapy, and worse survival with cetuximab.
Patients had been randomized to potentially curative treatment with cisplatin, capecitabine, and radiation, with or without cetuximab (Erbitux). Six months of follow-up on 258 patients found significantly lower median overall survival in the cetuximab arm compared with the control group (22.1 months vs. 25.4 months) and fewer patients free of treatment failure (66% vs. 77%), Dr. Thomas Crosby reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The number of patients lost to follow-up before 26 weeks was similar between groups: 10 in the cetuximab group and 8 in the control group, he added.
Significantly fewer patients in the cetuximab arm were able to receive the full protocol dose of radiotherapy compared with the control arm (75% vs. 86%) and to complete all four cycles of cisplatin and capecitabine at full doses (77% vs. 90%) or reduced doses (69% vs. 85%), reported Dr. Crosby of Velindre Hospital, Cardiff, Wales.
The cetuximab group also showed significantly higher rates of grade 3 or 4 nonhematologic toxicities (78%) compared with the control arm (63%), primarily because of increases in cardiac toxicities (6% vs. 2%), dermatologic toxicities (22% vs. 4%), and metabolic toxicities (24% vs. 11%).
"The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer," Dr. Crosby said.
All patients were to receive four cycles of cisplatin 60 mg/m2 on day 1 and capecitabine 625 mg/m2 daily on days 1-21, with cycles three and four given concurrently with radiotherapy (60 Gy in 25 fractions). The cetuximab group also received 400 mg/m2 of the drug on day 1 of cycle three, followed by cetuximab 250 mg/m2 weekly.
Patients in the multicenter study, known as the SCOPE 1 trial, had a median age of 67 years in both groups.
Survival outcomes associated with chemoradiotherapy for localized, poor-prognosis esophageal cancer in SCOPE 1 were better than results previously reported in trials of radiotherapy or surgery for these cancers, he noted. Future research should look at improving definitive chemoradiotherapy by identifying biomarkers to help select patients for treatment and incorporating newer radiology techniques to intensify treatment, he suggested.
Definitive chemoradiotherapy is used in the United Kingdom predominantly for patients with esophageal cancer who are not candidates for surgery and is considered a standard of care for patients with localized squamous cell carcinoma of the esophagus, Dr. Crosby said.
Other previous studies have reported that cetuximab improved outcomes when added to chemotherapy for advanced colorectal or head and neck cancers, and when added to radiotherapy for localized squamous cell carcinomas of the head and neck, he said. A separate study recently reported worse outcomes when cetuximab was added to first-line chemotherapy for gastric cancer.
Dr. Crosby reported having no relevant financial disclosures. Cetuximab is a product of ImClone, a subsidiary of Eli Lilly and Bristol-Myers Squibb, that is licensed to Merck KGaA for marketing outside the United States. Some of his associates reported receiving research funding from Merck, AstraZeneca, or Roche.
SAN FRANCISCO – A phase II/III clinical trial of adding cetuximab to chemoradiotherapy for localized esophageal cancer was stopped early when interim results showed greater toxicity, less completion of chemoradiotherapy, and worse survival with cetuximab.
Patients had been randomized to potentially curative treatment with cisplatin, capecitabine, and radiation, with or without cetuximab (Erbitux). Six months of follow-up on 258 patients found significantly lower median overall survival in the cetuximab arm compared with the control group (22.1 months vs. 25.4 months) and fewer patients free of treatment failure (66% vs. 77%), Dr. Thomas Crosby reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The number of patients lost to follow-up before 26 weeks was similar between groups: 10 in the cetuximab group and 8 in the control group, he added.
Significantly fewer patients in the cetuximab arm were able to receive the full protocol dose of radiotherapy compared with the control arm (75% vs. 86%) and to complete all four cycles of cisplatin and capecitabine at full doses (77% vs. 90%) or reduced doses (69% vs. 85%), reported Dr. Crosby of Velindre Hospital, Cardiff, Wales.
The cetuximab group also showed significantly higher rates of grade 3 or 4 nonhematologic toxicities (78%) compared with the control arm (63%), primarily because of increases in cardiac toxicities (6% vs. 2%), dermatologic toxicities (22% vs. 4%), and metabolic toxicities (24% vs. 11%).
"The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer," Dr. Crosby said.
All patients were to receive four cycles of cisplatin 60 mg/m2 on day 1 and capecitabine 625 mg/m2 daily on days 1-21, with cycles three and four given concurrently with radiotherapy (60 Gy in 25 fractions). The cetuximab group also received 400 mg/m2 of the drug on day 1 of cycle three, followed by cetuximab 250 mg/m2 weekly.
Patients in the multicenter study, known as the SCOPE 1 trial, had a median age of 67 years in both groups.
Survival outcomes associated with chemoradiotherapy for localized, poor-prognosis esophageal cancer in SCOPE 1 were better than results previously reported in trials of radiotherapy or surgery for these cancers, he noted. Future research should look at improving definitive chemoradiotherapy by identifying biomarkers to help select patients for treatment and incorporating newer radiology techniques to intensify treatment, he suggested.
Definitive chemoradiotherapy is used in the United Kingdom predominantly for patients with esophageal cancer who are not candidates for surgery and is considered a standard of care for patients with localized squamous cell carcinoma of the esophagus, Dr. Crosby said.
Other previous studies have reported that cetuximab improved outcomes when added to chemotherapy for advanced colorectal or head and neck cancers, and when added to radiotherapy for localized squamous cell carcinomas of the head and neck, he said. A separate study recently reported worse outcomes when cetuximab was added to first-line chemotherapy for gastric cancer.
Dr. Crosby reported having no relevant financial disclosures. Cetuximab is a product of ImClone, a subsidiary of Eli Lilly and Bristol-Myers Squibb, that is licensed to Merck KGaA for marketing outside the United States. Some of his associates reported receiving research funding from Merck, AstraZeneca, or Roche.
SAN FRANCISCO – A phase II/III clinical trial of adding cetuximab to chemoradiotherapy for localized esophageal cancer was stopped early when interim results showed greater toxicity, less completion of chemoradiotherapy, and worse survival with cetuximab.
Patients had been randomized to potentially curative treatment with cisplatin, capecitabine, and radiation, with or without cetuximab (Erbitux). Six months of follow-up on 258 patients found significantly lower median overall survival in the cetuximab arm compared with the control group (22.1 months vs. 25.4 months) and fewer patients free of treatment failure (66% vs. 77%), Dr. Thomas Crosby reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
The number of patients lost to follow-up before 26 weeks was similar between groups: 10 in the cetuximab group and 8 in the control group, he added.
Significantly fewer patients in the cetuximab arm were able to receive the full protocol dose of radiotherapy compared with the control arm (75% vs. 86%) and to complete all four cycles of cisplatin and capecitabine at full doses (77% vs. 90%) or reduced doses (69% vs. 85%), reported Dr. Crosby of Velindre Hospital, Cardiff, Wales.
The cetuximab group also showed significantly higher rates of grade 3 or 4 nonhematologic toxicities (78%) compared with the control arm (63%), primarily because of increases in cardiac toxicities (6% vs. 2%), dermatologic toxicities (22% vs. 4%), and metabolic toxicities (24% vs. 11%).
"The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer," Dr. Crosby said.
All patients were to receive four cycles of cisplatin 60 mg/m2 on day 1 and capecitabine 625 mg/m2 daily on days 1-21, with cycles three and four given concurrently with radiotherapy (60 Gy in 25 fractions). The cetuximab group also received 400 mg/m2 of the drug on day 1 of cycle three, followed by cetuximab 250 mg/m2 weekly.
Patients in the multicenter study, known as the SCOPE 1 trial, had a median age of 67 years in both groups.
Survival outcomes associated with chemoradiotherapy for localized, poor-prognosis esophageal cancer in SCOPE 1 were better than results previously reported in trials of radiotherapy or surgery for these cancers, he noted. Future research should look at improving definitive chemoradiotherapy by identifying biomarkers to help select patients for treatment and incorporating newer radiology techniques to intensify treatment, he suggested.
Definitive chemoradiotherapy is used in the United Kingdom predominantly for patients with esophageal cancer who are not candidates for surgery and is considered a standard of care for patients with localized squamous cell carcinoma of the esophagus, Dr. Crosby said.
Other previous studies have reported that cetuximab improved outcomes when added to chemotherapy for advanced colorectal or head and neck cancers, and when added to radiotherapy for localized squamous cell carcinomas of the head and neck, he said. A separate study recently reported worse outcomes when cetuximab was added to first-line chemotherapy for gastric cancer.
Dr. Crosby reported having no relevant financial disclosures. Cetuximab is a product of ImClone, a subsidiary of Eli Lilly and Bristol-Myers Squibb, that is licensed to Merck KGaA for marketing outside the United States. Some of his associates reported receiving research funding from Merck, AstraZeneca, or Roche.
AT A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY ASCO
Major Finding: Adding cetuximab to chemoradiotherapy for localized esophageal cancer was associated with significantly shorter median survival compared with no cetuximab – 22.1 vs. 25.4 months.
Data Source: Six months of follow-up on 258 patients in a randomized, controlled multicenter trial.
Disclosures: Dr. Crosby reported having no relevant financial disclosures. Cetuximab is a product of ImClone, a subsidiary of Eli Lilly and Bristol-Myers Squibb, that is licensed to Merck KGaA for marketing outside the United States. Some of his associates reported receiving research funding from Merck, AstraZeneca, or Roche.
Second-line agent for gastroesophageal adenocarcinoma ups survival
SAN FRANCISCO – A phase III clinical trial of an experimental monoclonal antibody for patients failing first-line treatment of metastatic gastric or gastroesophageal junction adenocarcinoma increased median overall survival to 5.2 months, compared with 3.8 months on placebo.
The difference was statistically significant and the treatment effect generally was consistent across major subgroups of the 355 patients in the international, prospective, double-blind trial. At 6 months, 42% of patients on ramucirumab and 32% on placebo were alive. At 12 months, 18% on ramucirumab and 11% on placebo were alive, Dr. Charles S. Fuchs and his associates reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
Ramucirumab is a fully human IgG1 monoclonal antibody receptor antagonist designed to inhibit the receptor for vascular endothelial cell growth factor (VEGF), which is believed to contribute to gastric cancer pathogenesis.
The study randomized 238 patients to second-line treatment with IV ramucirumab 8 mg/kg plus best supportive care or placebo plus best supportive care every 2 weeks until disease progression, unacceptable toxicity, or death. All patients had shown disease progression within 4 months of treatment for metastatic disease or within 6 months of adjuvant therapy using first-line regimens containing platinum and/or fluoropyrimidine.
Among secondary outcomes, patients in the ramucirumab group showed a significantly longer interval to disease progression – 2.1 months, compared with 1.3 months on placebo – the intent-to-treat analysis found. At 12 weeks, 40% of patients in the ramucirumab group and 16% on placebo showed no disease progression, reported Dr. Fuchs, director of the gastrointestinal cancer center at the Dana Farber Cancer Institute, Boston.
Overall, 49% of patients on ramucirumab showed a complete or partial response or stable disease, compared with 23% on placebo, a significant difference.
Two patients in each group did not receive the drug or placebo. Among 351 patients who did, the proportions that died because of an adverse event were similar between groups – 11% on ramucirumab and 13% on placebo. The two groups did not differ significantly in rates of most individual adverse events, most commonly fatigue, abdominal pain, decreased appetite, or vomiting. Hypertension was more likely to develop in the ramucirumab group than the placebo group (16% vs. 8%), and grade 3 or higher hypertension was more common on ramucirumab (8% vs. 3% on placebo), though no patients on ramucirumab developed grade 4 hypertension.
No unexpected or new findings regarding safety were seen, Dr. Fuchs reported. Hypertension is one of the adverse events generally associated with antiangiogenic agents and therapeutic antibodies. Rates did not differ between groups for other adverse events of special interest with these agents, including bleeding/hemorrhage, arteriothromboembolic or venous thrombolic events, proteinuria, GI perforation, fistula, and others.
Patient characteristics were similar between the groups at baseline.
The study enrolled patients at 120 centers in 30 countries on six continents.
Ramucirumab is a potential new second-line treatment for patients with metastatic adenocarcinoma of the stomach or the gastroesophageal junction, Dr. Fuchs suggested.
The symposium was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The study was funded by ImClone Systems, a subsidiary of Eli Lilly and Co., which is developing ramucirumab. Some of Dr. Fuchs’ associates in the study disclosed employment or other financial relationships with ImClone Systems and stock ownership in Eli Lilly. Dr. Fuchs has been an advisor to Amgen, Bayer, Bristol-Myers Squibb, Genentech, Infinity Pharmaceuticals, Metamark Genetics, Momenta Pharmaceuticals, Pfizer, Roche, and Sanofi.
On Twitter @sherryboschert
Charles S. Fuchs, gastrointestinal cancers sponsored by the American Society of Clinical Oncology, ASCO
SAN FRANCISCO – A phase III clinical trial of an experimental monoclonal antibody for patients failing first-line treatment of metastatic gastric or gastroesophageal junction adenocarcinoma increased median overall survival to 5.2 months, compared with 3.8 months on placebo.
The difference was statistically significant and the treatment effect generally was consistent across major subgroups of the 355 patients in the international, prospective, double-blind trial. At 6 months, 42% of patients on ramucirumab and 32% on placebo were alive. At 12 months, 18% on ramucirumab and 11% on placebo were alive, Dr. Charles S. Fuchs and his associates reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
Ramucirumab is a fully human IgG1 monoclonal antibody receptor antagonist designed to inhibit the receptor for vascular endothelial cell growth factor (VEGF), which is believed to contribute to gastric cancer pathogenesis.
The study randomized 238 patients to second-line treatment with IV ramucirumab 8 mg/kg plus best supportive care or placebo plus best supportive care every 2 weeks until disease progression, unacceptable toxicity, or death. All patients had shown disease progression within 4 months of treatment for metastatic disease or within 6 months of adjuvant therapy using first-line regimens containing platinum and/or fluoropyrimidine.
Among secondary outcomes, patients in the ramucirumab group showed a significantly longer interval to disease progression – 2.1 months, compared with 1.3 months on placebo – the intent-to-treat analysis found. At 12 weeks, 40% of patients in the ramucirumab group and 16% on placebo showed no disease progression, reported Dr. Fuchs, director of the gastrointestinal cancer center at the Dana Farber Cancer Institute, Boston.
Overall, 49% of patients on ramucirumab showed a complete or partial response or stable disease, compared with 23% on placebo, a significant difference.
Two patients in each group did not receive the drug or placebo. Among 351 patients who did, the proportions that died because of an adverse event were similar between groups – 11% on ramucirumab and 13% on placebo. The two groups did not differ significantly in rates of most individual adverse events, most commonly fatigue, abdominal pain, decreased appetite, or vomiting. Hypertension was more likely to develop in the ramucirumab group than the placebo group (16% vs. 8%), and grade 3 or higher hypertension was more common on ramucirumab (8% vs. 3% on placebo), though no patients on ramucirumab developed grade 4 hypertension.
No unexpected or new findings regarding safety were seen, Dr. Fuchs reported. Hypertension is one of the adverse events generally associated with antiangiogenic agents and therapeutic antibodies. Rates did not differ between groups for other adverse events of special interest with these agents, including bleeding/hemorrhage, arteriothromboembolic or venous thrombolic events, proteinuria, GI perforation, fistula, and others.
Patient characteristics were similar between the groups at baseline.
The study enrolled patients at 120 centers in 30 countries on six continents.
Ramucirumab is a potential new second-line treatment for patients with metastatic adenocarcinoma of the stomach or the gastroesophageal junction, Dr. Fuchs suggested.
The symposium was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The study was funded by ImClone Systems, a subsidiary of Eli Lilly and Co., which is developing ramucirumab. Some of Dr. Fuchs’ associates in the study disclosed employment or other financial relationships with ImClone Systems and stock ownership in Eli Lilly. Dr. Fuchs has been an advisor to Amgen, Bayer, Bristol-Myers Squibb, Genentech, Infinity Pharmaceuticals, Metamark Genetics, Momenta Pharmaceuticals, Pfizer, Roche, and Sanofi.
On Twitter @sherryboschert
SAN FRANCISCO – A phase III clinical trial of an experimental monoclonal antibody for patients failing first-line treatment of metastatic gastric or gastroesophageal junction adenocarcinoma increased median overall survival to 5.2 months, compared with 3.8 months on placebo.
The difference was statistically significant and the treatment effect generally was consistent across major subgroups of the 355 patients in the international, prospective, double-blind trial. At 6 months, 42% of patients on ramucirumab and 32% on placebo were alive. At 12 months, 18% on ramucirumab and 11% on placebo were alive, Dr. Charles S. Fuchs and his associates reported in a poster presentation at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology (ASCO).
Ramucirumab is a fully human IgG1 monoclonal antibody receptor antagonist designed to inhibit the receptor for vascular endothelial cell growth factor (VEGF), which is believed to contribute to gastric cancer pathogenesis.
The study randomized 238 patients to second-line treatment with IV ramucirumab 8 mg/kg plus best supportive care or placebo plus best supportive care every 2 weeks until disease progression, unacceptable toxicity, or death. All patients had shown disease progression within 4 months of treatment for metastatic disease or within 6 months of adjuvant therapy using first-line regimens containing platinum and/or fluoropyrimidine.
Among secondary outcomes, patients in the ramucirumab group showed a significantly longer interval to disease progression – 2.1 months, compared with 1.3 months on placebo – the intent-to-treat analysis found. At 12 weeks, 40% of patients in the ramucirumab group and 16% on placebo showed no disease progression, reported Dr. Fuchs, director of the gastrointestinal cancer center at the Dana Farber Cancer Institute, Boston.
Overall, 49% of patients on ramucirumab showed a complete or partial response or stable disease, compared with 23% on placebo, a significant difference.
Two patients in each group did not receive the drug or placebo. Among 351 patients who did, the proportions that died because of an adverse event were similar between groups – 11% on ramucirumab and 13% on placebo. The two groups did not differ significantly in rates of most individual adverse events, most commonly fatigue, abdominal pain, decreased appetite, or vomiting. Hypertension was more likely to develop in the ramucirumab group than the placebo group (16% vs. 8%), and grade 3 or higher hypertension was more common on ramucirumab (8% vs. 3% on placebo), though no patients on ramucirumab developed grade 4 hypertension.
No unexpected or new findings regarding safety were seen, Dr. Fuchs reported. Hypertension is one of the adverse events generally associated with antiangiogenic agents and therapeutic antibodies. Rates did not differ between groups for other adverse events of special interest with these agents, including bleeding/hemorrhage, arteriothromboembolic or venous thrombolic events, proteinuria, GI perforation, fistula, and others.
Patient characteristics were similar between the groups at baseline.
The study enrolled patients at 120 centers in 30 countries on six continents.
Ramucirumab is a potential new second-line treatment for patients with metastatic adenocarcinoma of the stomach or the gastroesophageal junction, Dr. Fuchs suggested.
The symposium was cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The study was funded by ImClone Systems, a subsidiary of Eli Lilly and Co., which is developing ramucirumab. Some of Dr. Fuchs’ associates in the study disclosed employment or other financial relationships with ImClone Systems and stock ownership in Eli Lilly. Dr. Fuchs has been an advisor to Amgen, Bayer, Bristol-Myers Squibb, Genentech, Infinity Pharmaceuticals, Metamark Genetics, Momenta Pharmaceuticals, Pfizer, Roche, and Sanofi.
On Twitter @sherryboschert
Charles S. Fuchs, gastrointestinal cancers sponsored by the American Society of Clinical Oncology, ASCO
Charles S. Fuchs, gastrointestinal cancers sponsored by the American Society of Clinical Oncology, ASCO
AT A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Patients who failed first-line treatment for metastatic gastric or gastroesophageal junction adenocarcinoma lived a median of 5.2 months on second-line treatment with ramucirumab or 3.8 months on placebo.
Data Source: International, randomized, double-blind trial in 355 patients.
Disclosures: The study was funded by ImClone Systems, a subsidiary of Eli Lilly and Co., which is developing ramucirumab. Some of Dr. Fuchs’ associates in the study disclosed employment or other financial relationships with ImClone Systems and stock ownership in Eli Lilly. Dr. Fuchs has been an advisor to Amgen, Bayer, Bristol-Myers Squibb, Genentech, Infinity Pharmaceuticals, Metamark Genetics, Momenta Pharmaceuticals, Pfizer, Roche, and Sanofi.
Resecting residual gastrointestinal stromal tumors improved survival
SAN FRANCISCO – Surgically removing residual gastrointestinal stromal tumors in patients who respond to imatinib therapy significantly increased time to tumor progression to 88 months, compared with 43 months using imatinib alone, based on findings from a retrospective study of 134 patients.
After controlling for the effects of other risk factors, the surgery decreased threefold the likelihood of disease progression and decreased fivefold the risk of death, Dr. Seong Joon Park reported in a press briefing sponsored by the American Society of Clinical Oncology (ASCO). The press conference was held in advance of at a meeting on gastrointestinal cancers sponsored by ASCO and three other cancer organizations.
The findings support the widely adopted practice of removing residual tumors in these patients, despite the retrospective and observational design of the study, Dr. Park said. A prospective European study of similar design to this one terminated early due to poor patient enrollment. "It’s really hard to conduct a prospective study of this design," said Dr. Park of Asan Medical Center, Seoul, South Korea.
He and his associates reviewed the records of patients who showed at least 6 months of disease stabilization or response to imatinib (Gleevec) treatment, 92 of whom got the drug treatment alone and 42 of whom underwent surgery to remove residual tumors after a median of 19 months of imatinib therapy. The imatinib therapy was restarted after surgery. Median follow-up for the cohort as a whole was 59 months.
"This treatment strategy is worth trying as a clinical practice if the medical center is large enough to have an experienced multidisciplinary team and to have low morbidity and mortality associated with surgery," he said.
Each year, approximately 5,000 new cases of gastrointestinal stromal tumors are diagnosed in the United States, most often in the stomach and small intestine, though they can occur anywhere in or near the GI tract. Imatinib typically is first-line therapy, and 80%-85% of patients will respond to the treatment, he said. A majority of patients who respond to imatinib will have residual tumors, however, which are believed to contribute to the development of drug resistance, leading to the hypothesis that removing the residual tumors would improve survival.
In general, one-third of patients are candidates for surgical removal of residual lesions, depending on the tumor size and other tumor and patient characteristics, Dr. Park said.
The two patient groups in the study were similar except that the surgery group was significantly younger (51 vs. 58 years) and was less likely to have metastases in the peritoneum (41% in the surgery group vs. 61% in the control group).
As it is an aggressive and difficult treatment, surgery is more likely to be considered and recommended to younger patients who have a good performance status and, thus, less likely to be recommended in patients with multiple peritoneal metastases.
Factors associated with longer progression-free and overall survival included surgery and having an initial tumor size less than 150 mm, multivariate analyses showed. Female sex and having the KIT exon 11 mutation also were associated with longer progression-free survival. The researchers used propensity scores and inverse-probability-weighting adjustments to account for the effects of factors other than surgery.
The gastrointestinal cancers meeting, where Dr. Park will present the results, is cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Park reported having no financial disclosures.
On Twitter @sherryboschert
GI stromal tumors are an uncommon type of gastrointestinal tumor that can arise at many different places within the GI tract. This disease is notable because it’s really been a triumph of molecularly targeted therapy with imatinib (Gleevec), a drug that targets a particular molecular abnormality present in GI stromal tumors. Because of this, there is an extremely high response rate in patients with GI stromal tumors and drug therapy can control the disease for years.
Unfortunately, resistance ultimately develops to imatinib. This study provides provocative evidence that taking an aggressive approach surgically in addition to medical treatment with imatinib may result in longer survival of patients with GI stromal tumors.
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.
GI stromal tumors are an uncommon type of gastrointestinal tumor that can arise at many different places within the GI tract. This disease is notable because it’s really been a triumph of molecularly targeted therapy with imatinib (Gleevec), a drug that targets a particular molecular abnormality present in GI stromal tumors. Because of this, there is an extremely high response rate in patients with GI stromal tumors and drug therapy can control the disease for years.
Unfortunately, resistance ultimately develops to imatinib. This study provides provocative evidence that taking an aggressive approach surgically in addition to medical treatment with imatinib may result in longer survival of patients with GI stromal tumors.
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.
GI stromal tumors are an uncommon type of gastrointestinal tumor that can arise at many different places within the GI tract. This disease is notable because it’s really been a triumph of molecularly targeted therapy with imatinib (Gleevec), a drug that targets a particular molecular abnormality present in GI stromal tumors. Because of this, there is an extremely high response rate in patients with GI stromal tumors and drug therapy can control the disease for years.
Unfortunately, resistance ultimately develops to imatinib. This study provides provocative evidence that taking an aggressive approach surgically in addition to medical treatment with imatinib may result in longer survival of patients with GI stromal tumors.
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 – Surgically removing residual gastrointestinal stromal tumors in patients who respond to imatinib therapy significantly increased time to tumor progression to 88 months, compared with 43 months using imatinib alone, based on findings from a retrospective study of 134 patients.
After controlling for the effects of other risk factors, the surgery decreased threefold the likelihood of disease progression and decreased fivefold the risk of death, Dr. Seong Joon Park reported in a press briefing sponsored by the American Society of Clinical Oncology (ASCO). The press conference was held in advance of at a meeting on gastrointestinal cancers sponsored by ASCO and three other cancer organizations.
The findings support the widely adopted practice of removing residual tumors in these patients, despite the retrospective and observational design of the study, Dr. Park said. A prospective European study of similar design to this one terminated early due to poor patient enrollment. "It’s really hard to conduct a prospective study of this design," said Dr. Park of Asan Medical Center, Seoul, South Korea.
He and his associates reviewed the records of patients who showed at least 6 months of disease stabilization or response to imatinib (Gleevec) treatment, 92 of whom got the drug treatment alone and 42 of whom underwent surgery to remove residual tumors after a median of 19 months of imatinib therapy. The imatinib therapy was restarted after surgery. Median follow-up for the cohort as a whole was 59 months.
"This treatment strategy is worth trying as a clinical practice if the medical center is large enough to have an experienced multidisciplinary team and to have low morbidity and mortality associated with surgery," he said.
Each year, approximately 5,000 new cases of gastrointestinal stromal tumors are diagnosed in the United States, most often in the stomach and small intestine, though they can occur anywhere in or near the GI tract. Imatinib typically is first-line therapy, and 80%-85% of patients will respond to the treatment, he said. A majority of patients who respond to imatinib will have residual tumors, however, which are believed to contribute to the development of drug resistance, leading to the hypothesis that removing the residual tumors would improve survival.
In general, one-third of patients are candidates for surgical removal of residual lesions, depending on the tumor size and other tumor and patient characteristics, Dr. Park said.
The two patient groups in the study were similar except that the surgery group was significantly younger (51 vs. 58 years) and was less likely to have metastases in the peritoneum (41% in the surgery group vs. 61% in the control group).
As it is an aggressive and difficult treatment, surgery is more likely to be considered and recommended to younger patients who have a good performance status and, thus, less likely to be recommended in patients with multiple peritoneal metastases.
Factors associated with longer progression-free and overall survival included surgery and having an initial tumor size less than 150 mm, multivariate analyses showed. Female sex and having the KIT exon 11 mutation also were associated with longer progression-free survival. The researchers used propensity scores and inverse-probability-weighting adjustments to account for the effects of factors other than surgery.
The gastrointestinal cancers meeting, where Dr. Park will present the results, is cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Park reported having no financial disclosures.
On Twitter @sherryboschert
SAN FRANCISCO – Surgically removing residual gastrointestinal stromal tumors in patients who respond to imatinib therapy significantly increased time to tumor progression to 88 months, compared with 43 months using imatinib alone, based on findings from a retrospective study of 134 patients.
After controlling for the effects of other risk factors, the surgery decreased threefold the likelihood of disease progression and decreased fivefold the risk of death, Dr. Seong Joon Park reported in a press briefing sponsored by the American Society of Clinical Oncology (ASCO). The press conference was held in advance of at a meeting on gastrointestinal cancers sponsored by ASCO and three other cancer organizations.
The findings support the widely adopted practice of removing residual tumors in these patients, despite the retrospective and observational design of the study, Dr. Park said. A prospective European study of similar design to this one terminated early due to poor patient enrollment. "It’s really hard to conduct a prospective study of this design," said Dr. Park of Asan Medical Center, Seoul, South Korea.
He and his associates reviewed the records of patients who showed at least 6 months of disease stabilization or response to imatinib (Gleevec) treatment, 92 of whom got the drug treatment alone and 42 of whom underwent surgery to remove residual tumors after a median of 19 months of imatinib therapy. The imatinib therapy was restarted after surgery. Median follow-up for the cohort as a whole was 59 months.
"This treatment strategy is worth trying as a clinical practice if the medical center is large enough to have an experienced multidisciplinary team and to have low morbidity and mortality associated with surgery," he said.
Each year, approximately 5,000 new cases of gastrointestinal stromal tumors are diagnosed in the United States, most often in the stomach and small intestine, though they can occur anywhere in or near the GI tract. Imatinib typically is first-line therapy, and 80%-85% of patients will respond to the treatment, he said. A majority of patients who respond to imatinib will have residual tumors, however, which are believed to contribute to the development of drug resistance, leading to the hypothesis that removing the residual tumors would improve survival.
In general, one-third of patients are candidates for surgical removal of residual lesions, depending on the tumor size and other tumor and patient characteristics, Dr. Park said.
The two patient groups in the study were similar except that the surgery group was significantly younger (51 vs. 58 years) and was less likely to have metastases in the peritoneum (41% in the surgery group vs. 61% in the control group).
As it is an aggressive and difficult treatment, surgery is more likely to be considered and recommended to younger patients who have a good performance status and, thus, less likely to be recommended in patients with multiple peritoneal metastases.
Factors associated with longer progression-free and overall survival included surgery and having an initial tumor size less than 150 mm, multivariate analyses showed. Female sex and having the KIT exon 11 mutation also were associated with longer progression-free survival. The researchers used propensity scores and inverse-probability-weighting adjustments to account for the effects of factors other than surgery.
The gastrointestinal cancers meeting, where Dr. Park will present the results, is cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Park reported having no financial disclosures.
On Twitter @sherryboschert
FROM A PRESS BRIEFING SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Time to tumor progression was 88 months in 42 patients who had surgery for residual disease and 42 months in 92 patients given imatinib alone. Metastases in the peritoneum were present in 41% of the imatinib-and-surgery group and 61% of the imatinib-only group.
Data Source: Retrospective study of 134 patients with metastatic or recurrent gastrointestinal tumors who showed at least 6 months of disease stabilization or response to imatinib, 42 of whom had residual tumors resected.
Disclosures: Dr. Park reported having no financial disclosures.
Second-line docetaxel benefits seen for esophagogastric cancers
Results of a phase III trial support a common clinical practice – giving docetaxel as second-line chemotherapy to patients with advanced adenocarcinomas of the stomach or esophagus that progressed after first-line chemotherapy.
The randomized, controlled, open-label study showed significantly longer overall survival in 84 patients who received docetaxel (a median of 5.2 months), compared with 84 patients who received only "active symptom control" as second-line therapy (3.6 months), Dr. Hugo Ford reported. Active symptom control could include anything that the treating clinicians felt might be appropriate to manage symptoms, including radiotherapy, steroids, and supportive medications.
The finding bolsters previous, weaker evidence of survival benefit from second-line chemotherapy in these patients. Perhaps more important, though, is the current study’s finding of improved quality of life in patients who underwent second-line chemotherapy with docetaxel, compared with no second-line chemotherapy, he said.
Although scores for global quality of life and function did not differ significantly between groups, pain scores were significantly better in the treatment group than the control group, Dr. Ford said during a press briefing sponsored by the American Society for Clinical Oncology (ASCO).
"This is the first trial to show a quality of life benefit" from second-line chemotherapy in patients with esophagogastric cancer, "which is a very important finding in terms of informing patients about the likely benefits of the treatment we’re offering them," added Dr. Ford, director of cancer services at Addenbrooke’s Hospital, Cambridge, England. "Docetaxel should be a standard second-line treatment for esophagogastric adenocarcinoma."
He will present the findings in San Francisco on Jan. 24 at a meeting on gastrointestinal cancers sponsored by ASCO.
Clinicians in the United States and Europe commonly give second-line chemotherapy to patients with advanced esophagogastric cancers that progress after first-line treatment, despite a lack of strong evidence for the practice. Without second-line chemotherapy, the median survival time of patients who relapse after first-line chemotherapy for advanced esophagogastric adenocarcinoma is 3-4 months, previous data suggest.
Two separate trials recently reported small survival benefits from second-line chemotherapy using other drugs. A German study using irinotecan was too small (only 40 patients) to be considered robust evidence, Dr. Ford said. A Korean study used either irinotecan or docetaxel for second-line therapy but included only gastric cancers in patients who were Asian and younger and fitter than patients normally seen in U.S. practices, he added.
Paclitaxel also is used commonly as second-line chemotherapy for esophagogastric cancers and similar to docetaxel. Although there are no randomized data showing benefits from second-line paclitaxel, compared with supportive care, "one would be reasonable extrapolating a benefit there," he said.
The current trial enrolled patients with locally advanced or metastatic esophagogastric cancer who had a performance status of 0-2 and whose cancer had progressed within 6 months of first-line chemotherapy with platinum/fluoropyrimidine. Patients randomized to second-line docetaxel received IV 75 mg/m2 every 3 weeks for up to six cycles.
Only 19 patients in the docetaxel group completed six cycles of the chemotherapy (23%); the median number of cycles was three per patient. Disease progression and toxicity were the main reasons for not completing six cycles. Grade 4 toxicity occurred in 18 patients on docetaxel (21%).
Nearly a third of patients in the docetaxel group received either one round or no chemotherapy, which points to the generally poor prognosis with this aggressive disease and the fact that a significant number of patients will not benefit from chemotherapy, Dr. Ford said.
"For me, it makes the case that in those people that are benefitting from chemotherapy, the benefits are probably more marked even than we saw in the trial," he said.
The study was unable to identify any subgroup as being less likely to benefit from second-line chemotherapy. Future studies may try to find ways to identify patients who won’t benefit from the treatment, he said.
"Docetaxel should be standard second-line treatment for esophagogastric adenocarcinoma, and we think it’s likely to be the standard arm against which future treatments should be compared," Dr. Ford said.
After second-line chemotherapy, 7% of patients had a partial response, and 46% had stable disease.
The median age in the study was 65 years, and 81% of patients were male. The performance status at randomization was 0 in 27% of patients, 1 in 57%, and 2 in 15%. A total of 46% of cancers were in the stomach, 34% were in the esophagogastric junction, and 20% were in the esophagus. The disease had metastasized in 86% of patients.
Disease progression occurred during primary chemotherapy in 43% of patients, within 3 months of finishing primary chemotherapy in 28%, and between 3 and 6 months after primary chemotherapy in 29% of patients.
Dr. Ford and his associates now are analyzing cost-effectiveness data collected during the study.
Approximately 39,000 new cases of esophagogastric cancer are diagnosed each year in the United States and 1.5 million cases worldwide, most commonly adenocarcinomas. All patients with esophagogastric adenocarcinoma who present with advanced disease and 60%-70% of patients who present with local disease will relapse after first-line chemotherapy.
The gastrointestinal cancers meeting, where Dr. Ford will present the results, is cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The charity Cancer Research UK funded the study. Sanofi-Aventis, which makes docetaxel, provided the drug for free. Some of Dr. Ford’s associates in the study have been consultants or advisers to Sanofi and/or received honoraria or research funding from the company.
It’s extremely difficult to conduct studies comparing an active therapy like chemotherapy treatment vs. a supportive care approach, because patients and their physicians tend to have biases that make random assignment particularly difficult to accept. That said, there are important questions in oncology for which a supportive care arm is appropriate, both because treatments often have side effects, and there’s concern for worsening of quality of life, and there are situations where treatment is commonly given, but there may not be the level of evidence you’d like to see, like we have in front-line therapy.
This very important study shows two things: One, that second-line therapy in patients with esophagus and gastric cancers is of benefit in prolonging survival. In addition, there’s a quality of life benefit – so there’s not detriment to patients from the side effects of this treatment.
 |
|
It’s really important to note that supportive care isn’t no-therapy. Supportive care means that there is an agreement that the goals of therapy are different than the goals of curative chemotherapy. But it’s still treatment, it’s still aggressive treatment, and it has specific goals.
There’s a lot of concern amongst the oncology community and beyond about how we approach the care of patients at the extremes, at the very end of life. There is significant evidence that a lot of treatment is given to patients within weeks of their death. Because treatment is toxic, we’re very cognizant of the question of whether patients are being harmed by this type of aggressive therapy.
This study is a critical type of study for providing an evidence base to help guide our treatment decisions at points in times when the goals are palliative and not curative, and where we’re talking about modest prolongations in survival. This is really a model for a type of study that we’d like to see more of, both from a clinical outcomes point of view and, of course, when evaluating health care costs.
Oncology, as a field, is one of the most clearly evidence-based fields of medicine. Most of what we do is based on high levels of evidence. Treatment towards the end of life is an area where perhaps we’ve fallen a little short and need to pay additional attention.
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 adviser to Precision Therapeutics.
It’s extremely difficult to conduct studies comparing an active therapy like chemotherapy treatment vs. a supportive care approach, because patients and their physicians tend to have biases that make random assignment particularly difficult to accept. That said, there are important questions in oncology for which a supportive care arm is appropriate, both because treatments often have side effects, and there’s concern for worsening of quality of life, and there are situations where treatment is commonly given, but there may not be the level of evidence you’d like to see, like we have in front-line therapy.
This very important study shows two things: One, that second-line therapy in patients with esophagus and gastric cancers is of benefit in prolonging survival. In addition, there’s a quality of life benefit – so there’s not detriment to patients from the side effects of this treatment.
|
|
It’s really important to note that supportive care isn’t no-therapy. Supportive care means that there is an agreement that the goals of therapy are different than the goals of curative chemotherapy. But it’s still treatment, it’s still aggressive treatment, and it has specific goals.
There’s a lot of concern amongst the oncology community and beyond about how we approach the care of patients at the extremes, at the very end of life. There is significant evidence that a lot of treatment is given to patients within weeks of their death. Because treatment is toxic, we’re very cognizant of the question of whether patients are being harmed by this type of aggressive therapy.
This study is a critical type of study for providing an evidence base to help guide our treatment decisions at points in times when the goals are palliative and not curative, and where we’re talking about modest prolongations in survival. This is really a model for a type of study that we’d like to see more of, both from a clinical outcomes point of view and, of course, when evaluating health care costs.
Oncology, as a field, is one of the most clearly evidence-based fields of medicine. Most of what we do is based on high levels of evidence. Treatment towards the end of life is an area where perhaps we’ve fallen a little short and need to pay additional attention.
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 adviser to Precision Therapeutics.
It’s extremely difficult to conduct studies comparing an active therapy like chemotherapy treatment vs. a supportive care approach, because patients and their physicians tend to have biases that make random assignment particularly difficult to accept. That said, there are important questions in oncology for which a supportive care arm is appropriate, both because treatments often have side effects, and there’s concern for worsening of quality of life, and there are situations where treatment is commonly given, but there may not be the level of evidence you’d like to see, like we have in front-line therapy.
This very important study shows two things: One, that second-line therapy in patients with esophagus and gastric cancers is of benefit in prolonging survival. In addition, there’s a quality of life benefit – so there’s not detriment to patients from the side effects of this treatment.
|
|
It’s really important to note that supportive care isn’t no-therapy. Supportive care means that there is an agreement that the goals of therapy are different than the goals of curative chemotherapy. But it’s still treatment, it’s still aggressive treatment, and it has specific goals.
There’s a lot of concern amongst the oncology community and beyond about how we approach the care of patients at the extremes, at the very end of life. There is significant evidence that a lot of treatment is given to patients within weeks of their death. Because treatment is toxic, we’re very cognizant of the question of whether patients are being harmed by this type of aggressive therapy.
This study is a critical type of study for providing an evidence base to help guide our treatment decisions at points in times when the goals are palliative and not curative, and where we’re talking about modest prolongations in survival. This is really a model for a type of study that we’d like to see more of, both from a clinical outcomes point of view and, of course, when evaluating health care costs.
Oncology, as a field, is one of the most clearly evidence-based fields of medicine. Most of what we do is based on high levels of evidence. Treatment towards the end of life is an area where perhaps we’ve fallen a little short and need to pay additional attention.
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 adviser to Precision Therapeutics.
Results of a phase III trial support a common clinical practice – giving docetaxel as second-line chemotherapy to patients with advanced adenocarcinomas of the stomach or esophagus that progressed after first-line chemotherapy.
The randomized, controlled, open-label study showed significantly longer overall survival in 84 patients who received docetaxel (a median of 5.2 months), compared with 84 patients who received only "active symptom control" as second-line therapy (3.6 months), Dr. Hugo Ford reported. Active symptom control could include anything that the treating clinicians felt might be appropriate to manage symptoms, including radiotherapy, steroids, and supportive medications.
The finding bolsters previous, weaker evidence of survival benefit from second-line chemotherapy in these patients. Perhaps more important, though, is the current study’s finding of improved quality of life in patients who underwent second-line chemotherapy with docetaxel, compared with no second-line chemotherapy, he said.
Although scores for global quality of life and function did not differ significantly between groups, pain scores were significantly better in the treatment group than the control group, Dr. Ford said during a press briefing sponsored by the American Society for Clinical Oncology (ASCO).
"This is the first trial to show a quality of life benefit" from second-line chemotherapy in patients with esophagogastric cancer, "which is a very important finding in terms of informing patients about the likely benefits of the treatment we’re offering them," added Dr. Ford, director of cancer services at Addenbrooke’s Hospital, Cambridge, England. "Docetaxel should be a standard second-line treatment for esophagogastric adenocarcinoma."
He will present the findings in San Francisco on Jan. 24 at a meeting on gastrointestinal cancers sponsored by ASCO.
Clinicians in the United States and Europe commonly give second-line chemotherapy to patients with advanced esophagogastric cancers that progress after first-line treatment, despite a lack of strong evidence for the practice. Without second-line chemotherapy, the median survival time of patients who relapse after first-line chemotherapy for advanced esophagogastric adenocarcinoma is 3-4 months, previous data suggest.
Two separate trials recently reported small survival benefits from second-line chemotherapy using other drugs. A German study using irinotecan was too small (only 40 patients) to be considered robust evidence, Dr. Ford said. A Korean study used either irinotecan or docetaxel for second-line therapy but included only gastric cancers in patients who were Asian and younger and fitter than patients normally seen in U.S. practices, he added.
Paclitaxel also is used commonly as second-line chemotherapy for esophagogastric cancers and similar to docetaxel. Although there are no randomized data showing benefits from second-line paclitaxel, compared with supportive care, "one would be reasonable extrapolating a benefit there," he said.
The current trial enrolled patients with locally advanced or metastatic esophagogastric cancer who had a performance status of 0-2 and whose cancer had progressed within 6 months of first-line chemotherapy with platinum/fluoropyrimidine. Patients randomized to second-line docetaxel received IV 75 mg/m2 every 3 weeks for up to six cycles.
Only 19 patients in the docetaxel group completed six cycles of the chemotherapy (23%); the median number of cycles was three per patient. Disease progression and toxicity were the main reasons for not completing six cycles. Grade 4 toxicity occurred in 18 patients on docetaxel (21%).
Nearly a third of patients in the docetaxel group received either one round or no chemotherapy, which points to the generally poor prognosis with this aggressive disease and the fact that a significant number of patients will not benefit from chemotherapy, Dr. Ford said.
"For me, it makes the case that in those people that are benefitting from chemotherapy, the benefits are probably more marked even than we saw in the trial," he said.
The study was unable to identify any subgroup as being less likely to benefit from second-line chemotherapy. Future studies may try to find ways to identify patients who won’t benefit from the treatment, he said.
"Docetaxel should be standard second-line treatment for esophagogastric adenocarcinoma, and we think it’s likely to be the standard arm against which future treatments should be compared," Dr. Ford said.
After second-line chemotherapy, 7% of patients had a partial response, and 46% had stable disease.
The median age in the study was 65 years, and 81% of patients were male. The performance status at randomization was 0 in 27% of patients, 1 in 57%, and 2 in 15%. A total of 46% of cancers were in the stomach, 34% were in the esophagogastric junction, and 20% were in the esophagus. The disease had metastasized in 86% of patients.
Disease progression occurred during primary chemotherapy in 43% of patients, within 3 months of finishing primary chemotherapy in 28%, and between 3 and 6 months after primary chemotherapy in 29% of patients.
Dr. Ford and his associates now are analyzing cost-effectiveness data collected during the study.
Approximately 39,000 new cases of esophagogastric cancer are diagnosed each year in the United States and 1.5 million cases worldwide, most commonly adenocarcinomas. All patients with esophagogastric adenocarcinoma who present with advanced disease and 60%-70% of patients who present with local disease will relapse after first-line chemotherapy.
The gastrointestinal cancers meeting, where Dr. Ford will present the results, is cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The charity Cancer Research UK funded the study. Sanofi-Aventis, which makes docetaxel, provided the drug for free. Some of Dr. Ford’s associates in the study have been consultants or advisers to Sanofi and/or received honoraria or research funding from the company.
Results of a phase III trial support a common clinical practice – giving docetaxel as second-line chemotherapy to patients with advanced adenocarcinomas of the stomach or esophagus that progressed after first-line chemotherapy.
The randomized, controlled, open-label study showed significantly longer overall survival in 84 patients who received docetaxel (a median of 5.2 months), compared with 84 patients who received only "active symptom control" as second-line therapy (3.6 months), Dr. Hugo Ford reported. Active symptom control could include anything that the treating clinicians felt might be appropriate to manage symptoms, including radiotherapy, steroids, and supportive medications.
The finding bolsters previous, weaker evidence of survival benefit from second-line chemotherapy in these patients. Perhaps more important, though, is the current study’s finding of improved quality of life in patients who underwent second-line chemotherapy with docetaxel, compared with no second-line chemotherapy, he said.
Although scores for global quality of life and function did not differ significantly between groups, pain scores were significantly better in the treatment group than the control group, Dr. Ford said during a press briefing sponsored by the American Society for Clinical Oncology (ASCO).
"This is the first trial to show a quality of life benefit" from second-line chemotherapy in patients with esophagogastric cancer, "which is a very important finding in terms of informing patients about the likely benefits of the treatment we’re offering them," added Dr. Ford, director of cancer services at Addenbrooke’s Hospital, Cambridge, England. "Docetaxel should be a standard second-line treatment for esophagogastric adenocarcinoma."
He will present the findings in San Francisco on Jan. 24 at a meeting on gastrointestinal cancers sponsored by ASCO.
Clinicians in the United States and Europe commonly give second-line chemotherapy to patients with advanced esophagogastric cancers that progress after first-line treatment, despite a lack of strong evidence for the practice. Without second-line chemotherapy, the median survival time of patients who relapse after first-line chemotherapy for advanced esophagogastric adenocarcinoma is 3-4 months, previous data suggest.
Two separate trials recently reported small survival benefits from second-line chemotherapy using other drugs. A German study using irinotecan was too small (only 40 patients) to be considered robust evidence, Dr. Ford said. A Korean study used either irinotecan or docetaxel for second-line therapy but included only gastric cancers in patients who were Asian and younger and fitter than patients normally seen in U.S. practices, he added.
Paclitaxel also is used commonly as second-line chemotherapy for esophagogastric cancers and similar to docetaxel. Although there are no randomized data showing benefits from second-line paclitaxel, compared with supportive care, "one would be reasonable extrapolating a benefit there," he said.
The current trial enrolled patients with locally advanced or metastatic esophagogastric cancer who had a performance status of 0-2 and whose cancer had progressed within 6 months of first-line chemotherapy with platinum/fluoropyrimidine. Patients randomized to second-line docetaxel received IV 75 mg/m2 every 3 weeks for up to six cycles.
Only 19 patients in the docetaxel group completed six cycles of the chemotherapy (23%); the median number of cycles was three per patient. Disease progression and toxicity were the main reasons for not completing six cycles. Grade 4 toxicity occurred in 18 patients on docetaxel (21%).
Nearly a third of patients in the docetaxel group received either one round or no chemotherapy, which points to the generally poor prognosis with this aggressive disease and the fact that a significant number of patients will not benefit from chemotherapy, Dr. Ford said.
"For me, it makes the case that in those people that are benefitting from chemotherapy, the benefits are probably more marked even than we saw in the trial," he said.
The study was unable to identify any subgroup as being less likely to benefit from second-line chemotherapy. Future studies may try to find ways to identify patients who won’t benefit from the treatment, he said.
"Docetaxel should be standard second-line treatment for esophagogastric adenocarcinoma, and we think it’s likely to be the standard arm against which future treatments should be compared," Dr. Ford said.
After second-line chemotherapy, 7% of patients had a partial response, and 46% had stable disease.
The median age in the study was 65 years, and 81% of patients were male. The performance status at randomization was 0 in 27% of patients, 1 in 57%, and 2 in 15%. A total of 46% of cancers were in the stomach, 34% were in the esophagogastric junction, and 20% were in the esophagus. The disease had metastasized in 86% of patients.
Disease progression occurred during primary chemotherapy in 43% of patients, within 3 months of finishing primary chemotherapy in 28%, and between 3 and 6 months after primary chemotherapy in 29% of patients.
Dr. Ford and his associates now are analyzing cost-effectiveness data collected during the study.
Approximately 39,000 new cases of esophagogastric cancer are diagnosed each year in the United States and 1.5 million cases worldwide, most commonly adenocarcinomas. All patients with esophagogastric adenocarcinoma who present with advanced disease and 60%-70% of patients who present with local disease will relapse after first-line chemotherapy.
The gastrointestinal cancers meeting, where Dr. Ford will present the results, is cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
The charity Cancer Research UK funded the study. Sanofi-Aventis, which makes docetaxel, provided the drug for free. Some of Dr. Ford’s associates in the study have been consultants or advisers to Sanofi and/or received honoraria or research funding from the company.
FROM A PRESS BRIEFING SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Docetaxel significantly increased overall survival from a median of 3.6 months to 5.2 months and reduced pain scores in patients with esophagogastric adenocarcinoma that progressed after first-line chemotherapy.
Data Source: Multicenter, open-label study of 168 patients randomized to second-line chemotherapy with docetaxel or active control of symptoms with no second-line chemotherapy.
Disclosures: Cancer Research UK funded the study. Sanofi-Aventis, which makes docetaxel, provided the drug for free. Some of Dr. Ford’s associates in the study have been consultants or advisers to Sanofi and/or received honoraria or research funding from the company.
