Gastrointestinal Cancers Symposium 2014

SAN FRANCISCO – Circulating tumor cells may be useful for ascertaining both the presence and extent of pancreatic cancer, according to the findings of a prospective cohort study reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

A "nano-Velcro" assay to find circulating tumor cells (CTCs) was evaluated prospectively in 61 patients with suspicious pancreatic masses, two-thirds of whom were found to have pancreatic adenocarcinoma.

Finding at least one CTC/2 mL of blood had 71% sensitivity and 95% specificity for the presence of pancreatic cancer, and, among the patients with cancer, finding at least two CTCs/2 mL of blood had 69% sensitivity and 96% specificity for the presence of metastases, reported Dr. Jacob S. Ankeny of the department of surgery, University of California, Los Angeles.

"I think CTCs do have a potential role in aiding in our diagnosis of pancreas cancer and in discriminating which patients are at higher risk of having metastatic disease at the time of their disease presentation," said Dr. Ankeny.

"In our study, circulating tumor cells actually outperformed CA 19-9 [cancer antigen 19-9] for differentiating locoregional vs. metastatic disease, and as a result, I think they show marked promise as a biomarker at the time of disease presentation so that we can perform pretreatment staging and implement more effective initial therapies based on patient stage," he added.

Study limitations included the small sample size and the lack of outcome data, Dr. Ankeny acknowledged. "Additionally, we had minimal inclusion of inflammatory pancreatic conditions and didn’t have any patients with acute pancreatitis. It’s known that some other inflammatory conditions actually lead to false-positive results in some other circulating tumor cell platforms."

A key challenge to using CTCs is their rarity, according to invited discussant Rebecca A. Miksad of Harvard Medical School and the Beth Israel Deaconess Medical Center, both in Boston.

"In the data presented, the difference between cancer and no cancer is one CTC; similarly, the difference between metastatic and locoregional cancer is one CTC. Because CTCs are detected only in whole numbers, these close cutoffs raise questions about the accuracy, reliability, and reproducibility; in other words, will the same result be found in repeated analysis of the same sample and in different samples from the same patient," she commented.

"CTCs in pancreatic cancer are intriguing, although the role remains unclear," Dr. Miksad concluded. "The presented CTC data has a narrow diagnostic predictive window, and we may find with further work that the utility of CTCs as a test to detect the presence of pancreatic cancer may differ from its utility to assist with staging."

The nano-Velcro assay uses antibody-coated silicon nanowires to capture circulating cells with high efficiency, Dr. Ankeny explained. The captured cells are stained immunocytochemically, scanned with fluorescence microscopy, and counted.

In the study, a tumor cell was defined as a cell measuring at least 10 microns that had a DAPI-staining nucleus, was positive for cytokeratin, and was negative for the leukocyte marker CD45.

The investigators tested duplicate 2-mL aliquots from the study patients at the time of their presentation with suspicious pancreatic masses.

The 41 patients determined to have pancreatic adenocarcinoma were roughly equally distributed across tumor stages II, III, and IV. The other 20 patients had more than half a dozen pancreatic conditions, such as intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and serous cysts.

The assay identified CTCs in 71% of the patients with cancer, reported Dr. Ankeny, who disclosed no conflicts of interest related to the research.

A single patient in the control group was found to have a CTC, meaning a false-positive result. "That was a patient with a nondiagnostic FNA [fine-needle aspiration] of a large cyst containing a large solid component," he explained. "Unfortunately, the patient went elsewhere for surgery and refused surgery, and we don’t have any follow-up pathology. So it’s a theoretical false-positive in our non–adenocarcinoma group."

At an optimal diagnostic cutoff of at least one CTC/2 mL blood, the assay had a sensitivity of 71%, a specificity of 95%, a positive predictive value of 97%, and a negative predictive value of 59% for the presence of pancreatic cancer.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without cancer, Dr. Ankeny said.

Among the patients with cancer, at the optimal cutoff of two or more CTCs/2 mL of blood, the assay had a sensitivity of 69%, a specificity of 96%, and a positive predictive value of 92% for the presence of metastases.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without metastases.

A subset of seven patients with presumed stage II disease based on preoperative imaging were found to have liver metastases at the time of surgery. In five of them, preoperative blood samples showed at least two CTCs/2 mL, predicting metastatic disease.

"This indicates that CTCs may be potentially useful in predicting preoperative metastasis and directing patients toward more appropriate therapies while having them avoid potentially morbid surgery," Dr. Ankeny commented.

In a final analysis, CTCs were superior to CA 19-9 for discriminating between locoregional disease and metastatic disease, with an area under the receiver operating characteristic curve of 0.87 (P less than .001) vs. 0.69 (P = .06).

Dr. Ankeny disclosed no relevant conflicts of interest. Dr. Miksad disclosed no relevant conflicts of interest.

SAN FRANCISCO – Circulating tumor cells may be useful for ascertaining both the presence and extent of pancreatic cancer, according to the findings of a prospective cohort study reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

A "nano-Velcro" assay to find circulating tumor cells (CTCs) was evaluated prospectively in 61 patients with suspicious pancreatic masses, two-thirds of whom were found to have pancreatic adenocarcinoma.

Finding at least one CTC/2 mL of blood had 71% sensitivity and 95% specificity for the presence of pancreatic cancer, and, among the patients with cancer, finding at least two CTCs/2 mL of blood had 69% sensitivity and 96% specificity for the presence of metastases, reported Dr. Jacob S. Ankeny of the department of surgery, University of California, Los Angeles.

"I think CTCs do have a potential role in aiding in our diagnosis of pancreas cancer and in discriminating which patients are at higher risk of having metastatic disease at the time of their disease presentation," said Dr. Ankeny.

"In our study, circulating tumor cells actually outperformed CA 19-9 [cancer antigen 19-9] for differentiating locoregional vs. metastatic disease, and as a result, I think they show marked promise as a biomarker at the time of disease presentation so that we can perform pretreatment staging and implement more effective initial therapies based on patient stage," he added.

Study limitations included the small sample size and the lack of outcome data, Dr. Ankeny acknowledged. "Additionally, we had minimal inclusion of inflammatory pancreatic conditions and didn’t have any patients with acute pancreatitis. It’s known that some other inflammatory conditions actually lead to false-positive results in some other circulating tumor cell platforms."

A key challenge to using CTCs is their rarity, according to invited discussant Rebecca A. Miksad of Harvard Medical School and the Beth Israel Deaconess Medical Center, both in Boston.

"In the data presented, the difference between cancer and no cancer is one CTC; similarly, the difference between metastatic and locoregional cancer is one CTC. Because CTCs are detected only in whole numbers, these close cutoffs raise questions about the accuracy, reliability, and reproducibility; in other words, will the same result be found in repeated analysis of the same sample and in different samples from the same patient," she commented.

"CTCs in pancreatic cancer are intriguing, although the role remains unclear," Dr. Miksad concluded. "The presented CTC data has a narrow diagnostic predictive window, and we may find with further work that the utility of CTCs as a test to detect the presence of pancreatic cancer may differ from its utility to assist with staging."

The nano-Velcro assay uses antibody-coated silicon nanowires to capture circulating cells with high efficiency, Dr. Ankeny explained. The captured cells are stained immunocytochemically, scanned with fluorescence microscopy, and counted.

In the study, a tumor cell was defined as a cell measuring at least 10 microns that had a DAPI-staining nucleus, was positive for cytokeratin, and was negative for the leukocyte marker CD45.

The investigators tested duplicate 2-mL aliquots from the study patients at the time of their presentation with suspicious pancreatic masses.

The 41 patients determined to have pancreatic adenocarcinoma were roughly equally distributed across tumor stages II, III, and IV. The other 20 patients had more than half a dozen pancreatic conditions, such as intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and serous cysts.

The assay identified CTCs in 71% of the patients with cancer, reported Dr. Ankeny, who disclosed no conflicts of interest related to the research.

A single patient in the control group was found to have a CTC, meaning a false-positive result. "That was a patient with a nondiagnostic FNA [fine-needle aspiration] of a large cyst containing a large solid component," he explained. "Unfortunately, the patient went elsewhere for surgery and refused surgery, and we don’t have any follow-up pathology. So it’s a theoretical false-positive in our non–adenocarcinoma group."

At an optimal diagnostic cutoff of at least one CTC/2 mL blood, the assay had a sensitivity of 71%, a specificity of 95%, a positive predictive value of 97%, and a negative predictive value of 59% for the presence of pancreatic cancer.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without cancer, Dr. Ankeny said.

Among the patients with cancer, at the optimal cutoff of two or more CTCs/2 mL of blood, the assay had a sensitivity of 69%, a specificity of 96%, and a positive predictive value of 92% for the presence of metastases.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without metastases.

A subset of seven patients with presumed stage II disease based on preoperative imaging were found to have liver metastases at the time of surgery. In five of them, preoperative blood samples showed at least two CTCs/2 mL, predicting metastatic disease.

"This indicates that CTCs may be potentially useful in predicting preoperative metastasis and directing patients toward more appropriate therapies while having them avoid potentially morbid surgery," Dr. Ankeny commented.

In a final analysis, CTCs were superior to CA 19-9 for discriminating between locoregional disease and metastatic disease, with an area under the receiver operating characteristic curve of 0.87 (P less than .001) vs. 0.69 (P = .06).

Dr. Ankeny disclosed no relevant conflicts of interest. Dr. Miksad disclosed no relevant conflicts of interest.

SAN FRANCISCO – Circulating tumor cells may be useful for ascertaining both the presence and extent of pancreatic cancer, according to the findings of a prospective cohort study reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

A "nano-Velcro" assay to find circulating tumor cells (CTCs) was evaluated prospectively in 61 patients with suspicious pancreatic masses, two-thirds of whom were found to have pancreatic adenocarcinoma.

Finding at least one CTC/2 mL of blood had 71% sensitivity and 95% specificity for the presence of pancreatic cancer, and, among the patients with cancer, finding at least two CTCs/2 mL of blood had 69% sensitivity and 96% specificity for the presence of metastases, reported Dr. Jacob S. Ankeny of the department of surgery, University of California, Los Angeles.

"I think CTCs do have a potential role in aiding in our diagnosis of pancreas cancer and in discriminating which patients are at higher risk of having metastatic disease at the time of their disease presentation," said Dr. Ankeny.

"In our study, circulating tumor cells actually outperformed CA 19-9 [cancer antigen 19-9] for differentiating locoregional vs. metastatic disease, and as a result, I think they show marked promise as a biomarker at the time of disease presentation so that we can perform pretreatment staging and implement more effective initial therapies based on patient stage," he added.

Study limitations included the small sample size and the lack of outcome data, Dr. Ankeny acknowledged. "Additionally, we had minimal inclusion of inflammatory pancreatic conditions and didn’t have any patients with acute pancreatitis. It’s known that some other inflammatory conditions actually lead to false-positive results in some other circulating tumor cell platforms."

A key challenge to using CTCs is their rarity, according to invited discussant Rebecca A. Miksad of Harvard Medical School and the Beth Israel Deaconess Medical Center, both in Boston.

"In the data presented, the difference between cancer and no cancer is one CTC; similarly, the difference between metastatic and locoregional cancer is one CTC. Because CTCs are detected only in whole numbers, these close cutoffs raise questions about the accuracy, reliability, and reproducibility; in other words, will the same result be found in repeated analysis of the same sample and in different samples from the same patient," she commented.

"CTCs in pancreatic cancer are intriguing, although the role remains unclear," Dr. Miksad concluded. "The presented CTC data has a narrow diagnostic predictive window, and we may find with further work that the utility of CTCs as a test to detect the presence of pancreatic cancer may differ from its utility to assist with staging."

The nano-Velcro assay uses antibody-coated silicon nanowires to capture circulating cells with high efficiency, Dr. Ankeny explained. The captured cells are stained immunocytochemically, scanned with fluorescence microscopy, and counted.

In the study, a tumor cell was defined as a cell measuring at least 10 microns that had a DAPI-staining nucleus, was positive for cytokeratin, and was negative for the leukocyte marker CD45.

The investigators tested duplicate 2-mL aliquots from the study patients at the time of their presentation with suspicious pancreatic masses.

The 41 patients determined to have pancreatic adenocarcinoma were roughly equally distributed across tumor stages II, III, and IV. The other 20 patients had more than half a dozen pancreatic conditions, such as intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and serous cysts.

The assay identified CTCs in 71% of the patients with cancer, reported Dr. Ankeny, who disclosed no conflicts of interest related to the research.

A single patient in the control group was found to have a CTC, meaning a false-positive result. "That was a patient with a nondiagnostic FNA [fine-needle aspiration] of a large cyst containing a large solid component," he explained. "Unfortunately, the patient went elsewhere for surgery and refused surgery, and we don’t have any follow-up pathology. So it’s a theoretical false-positive in our non–adenocarcinoma group."

At an optimal diagnostic cutoff of at least one CTC/2 mL blood, the assay had a sensitivity of 71%, a specificity of 95%, a positive predictive value of 97%, and a negative predictive value of 59% for the presence of pancreatic cancer.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without cancer, Dr. Ankeny said.

Among the patients with cancer, at the optimal cutoff of two or more CTCs/2 mL of blood, the assay had a sensitivity of 69%, a specificity of 96%, and a positive predictive value of 92% for the presence of metastases.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without metastases.

A subset of seven patients with presumed stage II disease based on preoperative imaging were found to have liver metastases at the time of surgery. In five of them, preoperative blood samples showed at least two CTCs/2 mL, predicting metastatic disease.

"This indicates that CTCs may be potentially useful in predicting preoperative metastasis and directing patients toward more appropriate therapies while having them avoid potentially morbid surgery," Dr. Ankeny commented.

In a final analysis, CTCs were superior to CA 19-9 for discriminating between locoregional disease and metastatic disease, with an area under the receiver operating characteristic curve of 0.87 (P less than .001) vs. 0.69 (P = .06).

Dr. Ankeny disclosed no relevant conflicts of interest. Dr. Miksad disclosed no relevant conflicts of interest.

SAN FRANCISCO – Postoperative complications are prognostic for poor outcomes in patients undergoing resection of gastric cancer, researchers reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The team retrospectively analyzed data collected in the U.S. Gastric Cancer Collaborative, a joint effort of seven moderate- to high-volume academic institutions across the United States. Analyses were based on 850 patients who underwent curative resection of gastric or gastroesophageal junction adenocarcinoma by abdominal approach from 2000 to 2012.

Complications occurred within a month of surgery in 40% of the patients, reported coauthor Dr. Ryan C. Fields of Washington University in St. Louis. These patients were 20% less likely to receive adjuvant therapy than were their peers with an uncomplicated postoperative course. And during a median follow-up of almost 3 years, those with postop complications were 60% more likely to die after potential confounding factors were taken into account.

"The particular strength of this data set is the cross-section of real-world treatments and outcomes that it represents," Dr. Fields noted.

Patients who had complications were older, had higher levels of comorbidity and complexity, underwent more extensive surgery, and had more advanced disease. "We could potentially identify preoperatively [these patients] in an attempt to reduce the chance of complications," he said.

Not included in this analysis was "the finding of muscular sarcopenia as measured from the psoas muscle on a preoperative CT scan. There are ongoing studies using this measure to identify patients who may benefit from a short course of intensive physical therapy and nutritional supplementation prior to surgery in an attempt to reduce complications," he added.

The study was limited by its retrospective and nonrandomized design, and factors such as selection bias and missing data may have affected outcomes, Dr. Fields acknowledged. The researchers are therefore conducting further analyses using propensity matching and imputation.

The data set "may not be representative of (patients in) other countries or importantly of the nearly 40% of patients with gastric cancer that are treated at non-university, community-based hospitals in the United States," he added. "I would argue, however, that if we accept the relationship between volume and outcomes that has been shown to be significant in gastrectomy, the effect of complications on outcomes would be expected to be even more significant in these settings."

Groups stratified by Clavien-Dindo score were too small to draw definitive conclusions, but there were trends whereby worse complications had a greater negative impact on outcome, Dr. Fields said.

"One of the problems that we have – as an oncologic community –is there is no real consistent definition of complications in a lot of this literature," he added, which may be generating some of the disparate findings. For example, the severity of a wound infection can range widely, with more severe infections affecting decisions about whether to delay or even withhold adjuvant therapy.

In the study, there were a total of 699 complications in 342 patients, "highlighting the ... observation that often complications can beget further complications," according to Dr. Fields.

More than one-third of the complications (37%) were of Clavien-Dindo grade III or IV, requiring care more invasive than simple treatment at the bedside or with intravenous medications.

The most common were anemia/bleeding (12%), wound infections (8%), pneumonia (6%), and respiratory failure requiring reintubation (6%).

Relative to counterparts without complications, patients who had complications were on average significantly older and had significantly higher American Society of Anesthesiologists scores (reflecting greater preoperative comorbidity and complexity), more extensive and complex surgery, and more advanced cancer.

"Importantly, we did not find neoadjuvant therapy to be associated with an increase in postoperative complications, and this is consistent with literature in other solid tumor types, such as pancreatic cancer and rectal cancer," noted Dr. Fields, who disclosed no conflicts of interest related to the study. Also, the extent of lymphadenectomy was not associated with this outcome.

A minority of patients had a laparoscopic surgery, and the number was too small to say whether this factor influenced complication rate, he said.

"What we can surmise, one, from the literature, and two, is that the specific complications that are oftentimes reduced with laparoscopy and minimally invasive surgery certainly relate to wound infection and wound problems for sure," Dr. Fields commented. "So I think if we can do anything to achieve the same oncologic goals and reduce the morbidity of an operation, and improve the ability of patients to get on adjuvant therapy, that’s going to be critical. And laparoscopy may be a way to do that in gastric cancer. It may be more challenging in some of the bulkier, more advanced tumors to apply it globally, but I think it certainly holds promise for that exact point."

Overall, 60% of patients without complications received adjuvant therapy, compared with 48% of patients with complications (P = .001).

In multivariate analyses conducted after a median follow-up of 35 months, patients who experienced postoperative complications still had shorter median survival (25 vs. 45 months) and were more likely to die (hazard ratio, 1.6; P = .004).

Other significant risk factors were receipt of neoadjuvant therapy, perineural invasion, and stage III or IV disease.

Dr. Fields disclosed no relevant conflicts of interest.

SAN FRANCISCO – Postoperative complications are prognostic for poor outcomes in patients undergoing resection of gastric cancer, researchers reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The team retrospectively analyzed data collected in the U.S. Gastric Cancer Collaborative, a joint effort of seven moderate- to high-volume academic institutions across the United States. Analyses were based on 850 patients who underwent curative resection of gastric or gastroesophageal junction adenocarcinoma by abdominal approach from 2000 to 2012.

Complications occurred within a month of surgery in 40% of the patients, reported coauthor Dr. Ryan C. Fields of Washington University in St. Louis. These patients were 20% less likely to receive adjuvant therapy than were their peers with an uncomplicated postoperative course. And during a median follow-up of almost 3 years, those with postop complications were 60% more likely to die after potential confounding factors were taken into account.

"The particular strength of this data set is the cross-section of real-world treatments and outcomes that it represents," Dr. Fields noted.

Patients who had complications were older, had higher levels of comorbidity and complexity, underwent more extensive surgery, and had more advanced disease. "We could potentially identify preoperatively [these patients] in an attempt to reduce the chance of complications," he said.

Not included in this analysis was "the finding of muscular sarcopenia as measured from the psoas muscle on a preoperative CT scan. There are ongoing studies using this measure to identify patients who may benefit from a short course of intensive physical therapy and nutritional supplementation prior to surgery in an attempt to reduce complications," he added.

The study was limited by its retrospective and nonrandomized design, and factors such as selection bias and missing data may have affected outcomes, Dr. Fields acknowledged. The researchers are therefore conducting further analyses using propensity matching and imputation.

The data set "may not be representative of (patients in) other countries or importantly of the nearly 40% of patients with gastric cancer that are treated at non-university, community-based hospitals in the United States," he added. "I would argue, however, that if we accept the relationship between volume and outcomes that has been shown to be significant in gastrectomy, the effect of complications on outcomes would be expected to be even more significant in these settings."

Groups stratified by Clavien-Dindo score were too small to draw definitive conclusions, but there were trends whereby worse complications had a greater negative impact on outcome, Dr. Fields said.

"One of the problems that we have – as an oncologic community –is there is no real consistent definition of complications in a lot of this literature," he added, which may be generating some of the disparate findings. For example, the severity of a wound infection can range widely, with more severe infections affecting decisions about whether to delay or even withhold adjuvant therapy.

In the study, there were a total of 699 complications in 342 patients, "highlighting the ... observation that often complications can beget further complications," according to Dr. Fields.

More than one-third of the complications (37%) were of Clavien-Dindo grade III or IV, requiring care more invasive than simple treatment at the bedside or with intravenous medications.

The most common were anemia/bleeding (12%), wound infections (8%), pneumonia (6%), and respiratory failure requiring reintubation (6%).

Relative to counterparts without complications, patients who had complications were on average significantly older and had significantly higher American Society of Anesthesiologists scores (reflecting greater preoperative comorbidity and complexity), more extensive and complex surgery, and more advanced cancer.

"Importantly, we did not find neoadjuvant therapy to be associated with an increase in postoperative complications, and this is consistent with literature in other solid tumor types, such as pancreatic cancer and rectal cancer," noted Dr. Fields, who disclosed no conflicts of interest related to the study. Also, the extent of lymphadenectomy was not associated with this outcome.

A minority of patients had a laparoscopic surgery, and the number was too small to say whether this factor influenced complication rate, he said.

"What we can surmise, one, from the literature, and two, is that the specific complications that are oftentimes reduced with laparoscopy and minimally invasive surgery certainly relate to wound infection and wound problems for sure," Dr. Fields commented. "So I think if we can do anything to achieve the same oncologic goals and reduce the morbidity of an operation, and improve the ability of patients to get on adjuvant therapy, that’s going to be critical. And laparoscopy may be a way to do that in gastric cancer. It may be more challenging in some of the bulkier, more advanced tumors to apply it globally, but I think it certainly holds promise for that exact point."

Overall, 60% of patients without complications received adjuvant therapy, compared with 48% of patients with complications (P = .001).

In multivariate analyses conducted after a median follow-up of 35 months, patients who experienced postoperative complications still had shorter median survival (25 vs. 45 months) and were more likely to die (hazard ratio, 1.6; P = .004).

Other significant risk factors were receipt of neoadjuvant therapy, perineural invasion, and stage III or IV disease.

Dr. Fields disclosed no relevant conflicts of interest.

SAN FRANCISCO – Postoperative complications are prognostic for poor outcomes in patients undergoing resection of gastric cancer, researchers reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The team retrospectively analyzed data collected in the U.S. Gastric Cancer Collaborative, a joint effort of seven moderate- to high-volume academic institutions across the United States. Analyses were based on 850 patients who underwent curative resection of gastric or gastroesophageal junction adenocarcinoma by abdominal approach from 2000 to 2012.

Complications occurred within a month of surgery in 40% of the patients, reported coauthor Dr. Ryan C. Fields of Washington University in St. Louis. These patients were 20% less likely to receive adjuvant therapy than were their peers with an uncomplicated postoperative course. And during a median follow-up of almost 3 years, those with postop complications were 60% more likely to die after potential confounding factors were taken into account.

"The particular strength of this data set is the cross-section of real-world treatments and outcomes that it represents," Dr. Fields noted.

Patients who had complications were older, had higher levels of comorbidity and complexity, underwent more extensive surgery, and had more advanced disease. "We could potentially identify preoperatively [these patients] in an attempt to reduce the chance of complications," he said.

Not included in this analysis was "the finding of muscular sarcopenia as measured from the psoas muscle on a preoperative CT scan. There are ongoing studies using this measure to identify patients who may benefit from a short course of intensive physical therapy and nutritional supplementation prior to surgery in an attempt to reduce complications," he added.

The study was limited by its retrospective and nonrandomized design, and factors such as selection bias and missing data may have affected outcomes, Dr. Fields acknowledged. The researchers are therefore conducting further analyses using propensity matching and imputation.

The data set "may not be representative of (patients in) other countries or importantly of the nearly 40% of patients with gastric cancer that are treated at non-university, community-based hospitals in the United States," he added. "I would argue, however, that if we accept the relationship between volume and outcomes that has been shown to be significant in gastrectomy, the effect of complications on outcomes would be expected to be even more significant in these settings."

Groups stratified by Clavien-Dindo score were too small to draw definitive conclusions, but there were trends whereby worse complications had a greater negative impact on outcome, Dr. Fields said.

"One of the problems that we have – as an oncologic community –is there is no real consistent definition of complications in a lot of this literature," he added, which may be generating some of the disparate findings. For example, the severity of a wound infection can range widely, with more severe infections affecting decisions about whether to delay or even withhold adjuvant therapy.

In the study, there were a total of 699 complications in 342 patients, "highlighting the ... observation that often complications can beget further complications," according to Dr. Fields.

More than one-third of the complications (37%) were of Clavien-Dindo grade III or IV, requiring care more invasive than simple treatment at the bedside or with intravenous medications.

The most common were anemia/bleeding (12%), wound infections (8%), pneumonia (6%), and respiratory failure requiring reintubation (6%).

Relative to counterparts without complications, patients who had complications were on average significantly older and had significantly higher American Society of Anesthesiologists scores (reflecting greater preoperative comorbidity and complexity), more extensive and complex surgery, and more advanced cancer.

"Importantly, we did not find neoadjuvant therapy to be associated with an increase in postoperative complications, and this is consistent with literature in other solid tumor types, such as pancreatic cancer and rectal cancer," noted Dr. Fields, who disclosed no conflicts of interest related to the study. Also, the extent of lymphadenectomy was not associated with this outcome.

A minority of patients had a laparoscopic surgery, and the number was too small to say whether this factor influenced complication rate, he said.

"What we can surmise, one, from the literature, and two, is that the specific complications that are oftentimes reduced with laparoscopy and minimally invasive surgery certainly relate to wound infection and wound problems for sure," Dr. Fields commented. "So I think if we can do anything to achieve the same oncologic goals and reduce the morbidity of an operation, and improve the ability of patients to get on adjuvant therapy, that’s going to be critical. And laparoscopy may be a way to do that in gastric cancer. It may be more challenging in some of the bulkier, more advanced tumors to apply it globally, but I think it certainly holds promise for that exact point."

Overall, 60% of patients without complications received adjuvant therapy, compared with 48% of patients with complications (P = .001).

In multivariate analyses conducted after a median follow-up of 35 months, patients who experienced postoperative complications still had shorter median survival (25 vs. 45 months) and were more likely to die (hazard ratio, 1.6; P = .004).

Other significant risk factors were receipt of neoadjuvant therapy, perineural invasion, and stage III or IV disease.

Dr. Fields disclosed no relevant conflicts of interest.

SAN FRANCISCO – Circulating tumor cells may be useful for ascertaining both the presence and extent of pancreatic cancer, according to the findings of a prospective cohort study reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

A "nano-Velcro" assay to find circulating tumor cells (CTCs) was evaluated prospectively in 61 patients with suspicious pancreatic masses, two-thirds of whom were found to have pancreatic adenocarcinoma.

Finding at least one CTC/2 mL of blood had 71% sensitivity and 95% specificity for the presence of pancreatic cancer, and, among the patients with cancer, finding at least two CTCs/2 mL of blood had 69% sensitivity and 96% specificity for the presence of metastases, reported Dr. Jacob S. Ankeny of the department of surgery, University of California, Los Angeles.

"I think CTCs do have a potential role in aiding in our diagnosis of pancreas cancer and in discriminating which patients are at higher risk of having metastatic disease at the time of their disease presentation," said Dr. Ankeny.

"In our study, circulating tumor cells actually outperformed CA 19-9 [cancer antigen 19-9] for differentiating locoregional vs. metastatic disease, and as a result, I think they show marked promise as a biomarker at the time of disease presentation so that we can perform pretreatment staging and implement more effective initial therapies based on patient stage," he added.

Study limitations included the small sample size and the lack of outcome data, Dr. Ankeny acknowledged. "Additionally, we had minimal inclusion of inflammatory pancreatic conditions and didn’t have any patients with acute pancreatitis. It’s known that some other inflammatory conditions actually lead to false-positive results in some other circulating tumor cell platforms."

A key challenge to using CTCs is their rarity, according to invited discussant Rebecca A. Miksad of Harvard Medical School and the Beth Israel Deaconess Medical Center, both in Boston.

"In the data presented, the difference between cancer and no cancer is one CTC; similarly, the difference between metastatic and locoregional cancer is one CTC. Because CTCs are detected only in whole numbers, these close cutoffs raise questions about the accuracy, reliability, and reproducibility; in other words, will the same result be found in repeated analysis of the same sample and in different samples from the same patient," she commented.

"CTCs in pancreatic cancer are intriguing, although the role remains unclear," Dr. Miksad concluded. "The presented CTC data has a narrow diagnostic predictive window, and we may find with further work that the utility of CTCs as a test to detect the presence of pancreatic cancer may differ from its utility to assist with staging."

The nano-Velcro assay uses antibody-coated silicon nanowires to capture circulating cells with high efficiency, Dr. Ankeny explained. The captured cells are stained immunocytochemically, scanned with fluorescence microscopy, and counted.

In the study, a tumor cell was defined as a cell measuring at least 10 microns that had a DAPI-staining nucleus, was positive for cytokeratin, and was negative for the leukocyte marker CD45.

The investigators tested duplicate 2-mL aliquots from the study patients at the time of their presentation with suspicious pancreatic masses.

The 41 patients determined to have pancreatic adenocarcinoma were roughly equally distributed across tumor stages II, III, and IV. The other 20 patients had more than half a dozen pancreatic conditions, such as intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and serous cysts.

The assay identified CTCs in 71% of the patients with cancer, reported Dr. Ankeny, who disclosed no conflicts of interest related to the research.

A single patient in the control group was found to have a CTC, meaning a false-positive result. "That was a patient with a nondiagnostic FNA [fine-needle aspiration] of a large cyst containing a large solid component," he explained. "Unfortunately, the patient went elsewhere for surgery and refused surgery, and we don’t have any follow-up pathology. So it’s a theoretical false-positive in our non–adenocarcinoma group."

At an optimal diagnostic cutoff of at least one CTC/2 mL blood, the assay had a sensitivity of 71%, a specificity of 95%, a positive predictive value of 97%, and a negative predictive value of 59% for the presence of pancreatic cancer.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without cancer, Dr. Ankeny said.

Among the patients with cancer, at the optimal cutoff of two or more CTCs/2 mL of blood, the assay had a sensitivity of 69%, a specificity of 96%, and a positive predictive value of 92% for the presence of metastases.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without metastases.

A subset of seven patients with presumed stage II disease based on preoperative imaging were found to have liver metastases at the time of surgery. In five of them, preoperative blood samples showed at least two CTCs/2 mL, predicting metastatic disease.

"This indicates that CTCs may be potentially useful in predicting preoperative metastasis and directing patients toward more appropriate therapies while having them avoid potentially morbid surgery," Dr. Ankeny commented.

In a final analysis, CTCs were superior to CA 19-9 for discriminating between locoregional disease and metastatic disease, with an area under the receiver operating characteristic curve of 0.87 (P less than .001) vs. 0.69 (P = .06).

Dr. Ankeny disclosed no relevant conflicts of interest. Dr. Miksad disclosed no relevant conflicts of interest.

SAN FRANCISCO – Circulating tumor cells may be useful for ascertaining both the presence and extent of pancreatic cancer, according to the findings of a prospective cohort study reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

A "nano-Velcro" assay to find circulating tumor cells (CTCs) was evaluated prospectively in 61 patients with suspicious pancreatic masses, two-thirds of whom were found to have pancreatic adenocarcinoma.

Finding at least one CTC/2 mL of blood had 71% sensitivity and 95% specificity for the presence of pancreatic cancer, and, among the patients with cancer, finding at least two CTCs/2 mL of blood had 69% sensitivity and 96% specificity for the presence of metastases, reported Dr. Jacob S. Ankeny of the department of surgery, University of California, Los Angeles.

"I think CTCs do have a potential role in aiding in our diagnosis of pancreas cancer and in discriminating which patients are at higher risk of having metastatic disease at the time of their disease presentation," said Dr. Ankeny.

"In our study, circulating tumor cells actually outperformed CA 19-9 [cancer antigen 19-9] for differentiating locoregional vs. metastatic disease, and as a result, I think they show marked promise as a biomarker at the time of disease presentation so that we can perform pretreatment staging and implement more effective initial therapies based on patient stage," he added.

Study limitations included the small sample size and the lack of outcome data, Dr. Ankeny acknowledged. "Additionally, we had minimal inclusion of inflammatory pancreatic conditions and didn’t have any patients with acute pancreatitis. It’s known that some other inflammatory conditions actually lead to false-positive results in some other circulating tumor cell platforms."

A key challenge to using CTCs is their rarity, according to invited discussant Rebecca A. Miksad of Harvard Medical School and the Beth Israel Deaconess Medical Center, both in Boston.

"In the data presented, the difference between cancer and no cancer is one CTC; similarly, the difference between metastatic and locoregional cancer is one CTC. Because CTCs are detected only in whole numbers, these close cutoffs raise questions about the accuracy, reliability, and reproducibility; in other words, will the same result be found in repeated analysis of the same sample and in different samples from the same patient," she commented.

"CTCs in pancreatic cancer are intriguing, although the role remains unclear," Dr. Miksad concluded. "The presented CTC data has a narrow diagnostic predictive window, and we may find with further work that the utility of CTCs as a test to detect the presence of pancreatic cancer may differ from its utility to assist with staging."

The nano-Velcro assay uses antibody-coated silicon nanowires to capture circulating cells with high efficiency, Dr. Ankeny explained. The captured cells are stained immunocytochemically, scanned with fluorescence microscopy, and counted.

In the study, a tumor cell was defined as a cell measuring at least 10 microns that had a DAPI-staining nucleus, was positive for cytokeratin, and was negative for the leukocyte marker CD45.

The investigators tested duplicate 2-mL aliquots from the study patients at the time of their presentation with suspicious pancreatic masses.

The 41 patients determined to have pancreatic adenocarcinoma were roughly equally distributed across tumor stages II, III, and IV. The other 20 patients had more than half a dozen pancreatic conditions, such as intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and serous cysts.

The assay identified CTCs in 71% of the patients with cancer, reported Dr. Ankeny, who disclosed no conflicts of interest related to the research.

A single patient in the control group was found to have a CTC, meaning a false-positive result. "That was a patient with a nondiagnostic FNA [fine-needle aspiration] of a large cyst containing a large solid component," he explained. "Unfortunately, the patient went elsewhere for surgery and refused surgery, and we don’t have any follow-up pathology. So it’s a theoretical false-positive in our non–adenocarcinoma group."

At an optimal diagnostic cutoff of at least one CTC/2 mL blood, the assay had a sensitivity of 71%, a specificity of 95%, a positive predictive value of 97%, and a negative predictive value of 59% for the presence of pancreatic cancer.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without cancer, Dr. Ankeny said.

Among the patients with cancer, at the optimal cutoff of two or more CTCs/2 mL of blood, the assay had a sensitivity of 69%, a specificity of 96%, and a positive predictive value of 92% for the presence of metastases.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without metastases.

A subset of seven patients with presumed stage II disease based on preoperative imaging were found to have liver metastases at the time of surgery. In five of them, preoperative blood samples showed at least two CTCs/2 mL, predicting metastatic disease.

"This indicates that CTCs may be potentially useful in predicting preoperative metastasis and directing patients toward more appropriate therapies while having them avoid potentially morbid surgery," Dr. Ankeny commented.

In a final analysis, CTCs were superior to CA 19-9 for discriminating between locoregional disease and metastatic disease, with an area under the receiver operating characteristic curve of 0.87 (P less than .001) vs. 0.69 (P = .06).

Dr. Ankeny disclosed no relevant conflicts of interest. Dr. Miksad disclosed no relevant conflicts of interest.

SAN FRANCISCO – Circulating tumor cells may be useful for ascertaining both the presence and extent of pancreatic cancer, according to the findings of a prospective cohort study reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

A "nano-Velcro" assay to find circulating tumor cells (CTCs) was evaluated prospectively in 61 patients with suspicious pancreatic masses, two-thirds of whom were found to have pancreatic adenocarcinoma.

Finding at least one CTC/2 mL of blood had 71% sensitivity and 95% specificity for the presence of pancreatic cancer, and, among the patients with cancer, finding at least two CTCs/2 mL of blood had 69% sensitivity and 96% specificity for the presence of metastases, reported Dr. Jacob S. Ankeny of the department of surgery, University of California, Los Angeles.

"I think CTCs do have a potential role in aiding in our diagnosis of pancreas cancer and in discriminating which patients are at higher risk of having metastatic disease at the time of their disease presentation," said Dr. Ankeny.

"In our study, circulating tumor cells actually outperformed CA 19-9 [cancer antigen 19-9] for differentiating locoregional vs. metastatic disease, and as a result, I think they show marked promise as a biomarker at the time of disease presentation so that we can perform pretreatment staging and implement more effective initial therapies based on patient stage," he added.

Study limitations included the small sample size and the lack of outcome data, Dr. Ankeny acknowledged. "Additionally, we had minimal inclusion of inflammatory pancreatic conditions and didn’t have any patients with acute pancreatitis. It’s known that some other inflammatory conditions actually lead to false-positive results in some other circulating tumor cell platforms."

A key challenge to using CTCs is their rarity, according to invited discussant Rebecca A. Miksad of Harvard Medical School and the Beth Israel Deaconess Medical Center, both in Boston.

"In the data presented, the difference between cancer and no cancer is one CTC; similarly, the difference between metastatic and locoregional cancer is one CTC. Because CTCs are detected only in whole numbers, these close cutoffs raise questions about the accuracy, reliability, and reproducibility; in other words, will the same result be found in repeated analysis of the same sample and in different samples from the same patient," she commented.

"CTCs in pancreatic cancer are intriguing, although the role remains unclear," Dr. Miksad concluded. "The presented CTC data has a narrow diagnostic predictive window, and we may find with further work that the utility of CTCs as a test to detect the presence of pancreatic cancer may differ from its utility to assist with staging."

The nano-Velcro assay uses antibody-coated silicon nanowires to capture circulating cells with high efficiency, Dr. Ankeny explained. The captured cells are stained immunocytochemically, scanned with fluorescence microscopy, and counted.

In the study, a tumor cell was defined as a cell measuring at least 10 microns that had a DAPI-staining nucleus, was positive for cytokeratin, and was negative for the leukocyte marker CD45.

The investigators tested duplicate 2-mL aliquots from the study patients at the time of their presentation with suspicious pancreatic masses.

The 41 patients determined to have pancreatic adenocarcinoma were roughly equally distributed across tumor stages II, III, and IV. The other 20 patients had more than half a dozen pancreatic conditions, such as intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and serous cysts.

The assay identified CTCs in 71% of the patients with cancer, reported Dr. Ankeny, who disclosed no conflicts of interest related to the research.

A single patient in the control group was found to have a CTC, meaning a false-positive result. "That was a patient with a nondiagnostic FNA [fine-needle aspiration] of a large cyst containing a large solid component," he explained. "Unfortunately, the patient went elsewhere for surgery and refused surgery, and we don’t have any follow-up pathology. So it’s a theoretical false-positive in our non–adenocarcinoma group."

At an optimal diagnostic cutoff of at least one CTC/2 mL blood, the assay had a sensitivity of 71%, a specificity of 95%, a positive predictive value of 97%, and a negative predictive value of 59% for the presence of pancreatic cancer.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without cancer, Dr. Ankeny said.

Among the patients with cancer, at the optimal cutoff of two or more CTCs/2 mL of blood, the assay had a sensitivity of 69%, a specificity of 96%, and a positive predictive value of 92% for the presence of metastases.

The area under a receiver operating characteristic curve was 0.84 (P less than .001), indicating good discrimination between patients with and without metastases.

A subset of seven patients with presumed stage II disease based on preoperative imaging were found to have liver metastases at the time of surgery. In five of them, preoperative blood samples showed at least two CTCs/2 mL, predicting metastatic disease.

"This indicates that CTCs may be potentially useful in predicting preoperative metastasis and directing patients toward more appropriate therapies while having them avoid potentially morbid surgery," Dr. Ankeny commented.

In a final analysis, CTCs were superior to CA 19-9 for discriminating between locoregional disease and metastatic disease, with an area under the receiver operating characteristic curve of 0.87 (P less than .001) vs. 0.69 (P = .06).

Dr. Ankeny disclosed no relevant conflicts of interest. Dr. Miksad disclosed no relevant conflicts of interest.

SAN FRANCISCO – The incidence of colorectal cancer is rising sharply among younger adults in the United States, a study showed.

Researchers analyzed Surveillance, Epidemiology, and End Results (SEER) data for 383,241 patients in whom colorectal cancer was diagnosed between 1975 and 2010.

The results showed that the age-adjusted incidence rate of colorectal cancer fell steadily among patients aged 50 years and older at diagnosis, lead author Dr. Christina E. Bailey, a surgical oncology fellow at the M.D. Anderson Cancer Center in Houston, reported in a poster session at the annual Gastrointestinal Cancers Symposium. But the rate rose among younger patients.

The annual percentage change in the age-adjusted incidence rate of colorectal cancer during the 35-year period was a significant –0.92 in the cohort overall. In stratified analyses, the annual percentage change fell significantly among patients aged 50-74 at diagnosis (–0.97), and aged 75 years and older at diagnosis (–1.15). But it rose among patients aged 35-49 at diagnosis (0.41) and especially among patients aged 20-34 at diagnosis (1.99).

The findings were similar for colon cancer separately (with strongest results seen for disease that was distant at diagnosis) and for rectal/rectosigmoid cancer separately.

A predictive model suggested that if the observed trends persist between 2010 and 2030, the incidences of colon cancer and of rectal/rectosigmoid cancer will rise by 90% and 124%, respectively, among 20- to 34-year-olds, and by 28% and 46%, respectively, among 35- to 49-year-olds.

Much of the decreasing incidence among older adults "can be attributed to the fact that screening is recommended beginning at the age of 50," Dr. Bailey commented in an interview.

"We saw dramatic rises in the predicted incidences of both colon and rectal cancer in our younger cohort that point out that further studies need to be done to determine why this is happening and what can we do now to prevent this trajectory from occurring in the future," she said at the symposium, sponsored by the American Society of Clinical Oncology.

Likely explanations for this sharp uptick, she suggested, include increasing population levels of obesity and physical inactivity, and consumption of a diet high in fat and red meat – factors implicated as risks for colorectal cancer.

Another possibility is that primary care physicians are now more alert for this cancer in young patients with symptoms such as rectal bleeding, which previously may have been attributed to conditions such as hemorrhoids, delaying diagnosis until an older age.

Recommendations still call for routine colorectal cancer screening only in those patients younger than age 50 who have risk factors such as familial adenomatous polyposis and Lynch syndrome, Dr. Bailey noted. And even though the incidence is rising in the younger age groups, it is still considerably lower than it is among people aged 50 years and older.

Dr. Bailey said she had no relevant financial disclosures.

SAN FRANCISCO – The incidence of colorectal cancer is rising sharply among younger adults in the United States, a study showed.

Researchers analyzed Surveillance, Epidemiology, and End Results (SEER) data for 383,241 patients in whom colorectal cancer was diagnosed between 1975 and 2010.

The results showed that the age-adjusted incidence rate of colorectal cancer fell steadily among patients aged 50 years and older at diagnosis, lead author Dr. Christina E. Bailey, a surgical oncology fellow at the M.D. Anderson Cancer Center in Houston, reported in a poster session at the annual Gastrointestinal Cancers Symposium. But the rate rose among younger patients.

The annual percentage change in the age-adjusted incidence rate of colorectal cancer during the 35-year period was a significant –0.92 in the cohort overall. In stratified analyses, the annual percentage change fell significantly among patients aged 50-74 at diagnosis (–0.97), and aged 75 years and older at diagnosis (–1.15). But it rose among patients aged 35-49 at diagnosis (0.41) and especially among patients aged 20-34 at diagnosis (1.99).

The findings were similar for colon cancer separately (with strongest results seen for disease that was distant at diagnosis) and for rectal/rectosigmoid cancer separately.

A predictive model suggested that if the observed trends persist between 2010 and 2030, the incidences of colon cancer and of rectal/rectosigmoid cancer will rise by 90% and 124%, respectively, among 20- to 34-year-olds, and by 28% and 46%, respectively, among 35- to 49-year-olds.

Much of the decreasing incidence among older adults "can be attributed to the fact that screening is recommended beginning at the age of 50," Dr. Bailey commented in an interview.

"We saw dramatic rises in the predicted incidences of both colon and rectal cancer in our younger cohort that point out that further studies need to be done to determine why this is happening and what can we do now to prevent this trajectory from occurring in the future," she said at the symposium, sponsored by the American Society of Clinical Oncology.

Likely explanations for this sharp uptick, she suggested, include increasing population levels of obesity and physical inactivity, and consumption of a diet high in fat and red meat – factors implicated as risks for colorectal cancer.

Another possibility is that primary care physicians are now more alert for this cancer in young patients with symptoms such as rectal bleeding, which previously may have been attributed to conditions such as hemorrhoids, delaying diagnosis until an older age.

Recommendations still call for routine colorectal cancer screening only in those patients younger than age 50 who have risk factors such as familial adenomatous polyposis and Lynch syndrome, Dr. Bailey noted. And even though the incidence is rising in the younger age groups, it is still considerably lower than it is among people aged 50 years and older.

Dr. Bailey said she had no relevant financial disclosures.

SAN FRANCISCO – The incidence of colorectal cancer is rising sharply among younger adults in the United States, a study showed.

Researchers analyzed Surveillance, Epidemiology, and End Results (SEER) data for 383,241 patients in whom colorectal cancer was diagnosed between 1975 and 2010.

The results showed that the age-adjusted incidence rate of colorectal cancer fell steadily among patients aged 50 years and older at diagnosis, lead author Dr. Christina E. Bailey, a surgical oncology fellow at the M.D. Anderson Cancer Center in Houston, reported in a poster session at the annual Gastrointestinal Cancers Symposium. But the rate rose among younger patients.

The annual percentage change in the age-adjusted incidence rate of colorectal cancer during the 35-year period was a significant –0.92 in the cohort overall. In stratified analyses, the annual percentage change fell significantly among patients aged 50-74 at diagnosis (–0.97), and aged 75 years and older at diagnosis (–1.15). But it rose among patients aged 35-49 at diagnosis (0.41) and especially among patients aged 20-34 at diagnosis (1.99).

The findings were similar for colon cancer separately (with strongest results seen for disease that was distant at diagnosis) and for rectal/rectosigmoid cancer separately.

A predictive model suggested that if the observed trends persist between 2010 and 2030, the incidences of colon cancer and of rectal/rectosigmoid cancer will rise by 90% and 124%, respectively, among 20- to 34-year-olds, and by 28% and 46%, respectively, among 35- to 49-year-olds.

Much of the decreasing incidence among older adults "can be attributed to the fact that screening is recommended beginning at the age of 50," Dr. Bailey commented in an interview.

"We saw dramatic rises in the predicted incidences of both colon and rectal cancer in our younger cohort that point out that further studies need to be done to determine why this is happening and what can we do now to prevent this trajectory from occurring in the future," she said at the symposium, sponsored by the American Society of Clinical Oncology.

Likely explanations for this sharp uptick, she suggested, include increasing population levels of obesity and physical inactivity, and consumption of a diet high in fat and red meat – factors implicated as risks for colorectal cancer.

Another possibility is that primary care physicians are now more alert for this cancer in young patients with symptoms such as rectal bleeding, which previously may have been attributed to conditions such as hemorrhoids, delaying diagnosis until an older age.

Recommendations still call for routine colorectal cancer screening only in those patients younger than age 50 who have risk factors such as familial adenomatous polyposis and Lynch syndrome, Dr. Bailey noted. And even though the incidence is rising in the younger age groups, it is still considerably lower than it is among people aged 50 years and older.

Dr. Bailey said she had no relevant financial disclosures.

SAN FRANCISCO – Regular aspirin use did not improve outcomes among patients with colorectal cancers with mutations of the PIK3CA gene, suggest new data from the largest study yet of aspirin use in this patient population.

Regular aspirin use was reported by 26% of the 185 patients studied, researchers reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Users and nonusers were statistically indistinguishable with respect to a variety of recurrence- and survival-related outcomes, according to first author Dr. Nishi Kothari of the H. Lee Moffitt Cancer Center and Research Institute in Tampa.

"Our collaborative study did not validate overall or cancer-specific survival benefits associated with aspirin in PIK3CA-mutant patients across all stages, despite having a larger data set of patients" than earlier studies. "We were also not able to validate the recurrence-free survival benefits associated with aspirin in PIK3CA patients with stages II and III colorectal cancers."

The earlier health professionals study (N. Engl. J. Med. 2012;367:1596-606)and adjuvant VICTOR (Vioxx in Colorectal Cancer Therapy: Definition of Optimal Regime) trial (J. Clin. Oncol. 2013;31:4297-305) suggested that PIK3CA mutation, found in about 15% of colorectal cancers, is a biomarker for treatment benefit from aspirin.

Such research has been prompted by the known impact of constitutive PI3K signaling on cyclooxygenase-2 (COX-2) activity and prostaglandin E2 synthesis, blocking tumor cell apoptosis, according to Dr. Kothari. By inhibiting COX-2, aspirin may restore apoptosis.

Factors that may explain the studies’ differing results include differing patient populations, more advanced-stage disease in the new study, a relatively smaller share of right-sided primaries (which are associated with poorer survival) among patients with metastases, inclusion of patients with mutations of PIK3CA in exons 9 and 20 (which have an unclear impact on outcomes), and shorter follow-up.

"At this point, we have positive as well as negative results regarding the predictive value of PIK3CA for aspirin therapy. To help resolve this issue, we will contribute this data to an individual patient meta-analysis" encompassing all three studies, Dr. Kothari said. "To further explore the validity of PIK3CA as a predictive biomarker, a prospective randomized study design should be used."

"As we move into an era of next-generation sequencing, we need to consider which somatic mutations should be studied ... As we identify more mutations in PIK3CA and put together larger patient cohorts, prospective work on aspirin as targeted therapy can begin to evaluate outcomes by mutation," she added.

In the new study, the investigators performed targeted exome sequencing of tumors from patients with stage I to IV colorectal cancer treated at the Moffitt Cancer Center and Royal Melbourne Hospital to identify the cohort with PIK3CA mutations.

The primary colorectal cancer tumor was right sided in 107 patients, left sided in 77 patients, and of unknown location in 1 patient.

With a median follow-up of 46 months, aspirin users and nonusers had statistically indistinguishable overall survival and cancer-specific survival, reported Dr. Kothari. The findings remained the same in a multivariate analysis that included potential confounders.

Furthermore, there was no benefit in terms of recurrence-free survival among patients with stage II and III disease.

There was a trend toward better overall survival for aspirin users among patients with stage IV disease in univariate analysis (hazard ratio, 0.40; P = .06) but not in multivariate analysis.

"Of note, we did find a statistically significant worsened survival with right-sided cancers in this stage IV population," Dr. Kothari pointed out (HR for left vs. right, 0.43; P = .037). "The improved survival with aspirin use seen initially in our stage IV univariate analysis might thus be due to a decrease in incidence of right-sided cancers."

Dr. Kothari disclosed no relevant conflicts of interest.

SAN FRANCISCO – Regular aspirin use did not improve outcomes among patients with colorectal cancers with mutations of the PIK3CA gene, suggest new data from the largest study yet of aspirin use in this patient population.

Regular aspirin use was reported by 26% of the 185 patients studied, researchers reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Users and nonusers were statistically indistinguishable with respect to a variety of recurrence- and survival-related outcomes, according to first author Dr. Nishi Kothari of the H. Lee Moffitt Cancer Center and Research Institute in Tampa.

"Our collaborative study did not validate overall or cancer-specific survival benefits associated with aspirin in PIK3CA-mutant patients across all stages, despite having a larger data set of patients" than earlier studies. "We were also not able to validate the recurrence-free survival benefits associated with aspirin in PIK3CA patients with stages II and III colorectal cancers."

The earlier health professionals study (N. Engl. J. Med. 2012;367:1596-606)and adjuvant VICTOR (Vioxx in Colorectal Cancer Therapy: Definition of Optimal Regime) trial (J. Clin. Oncol. 2013;31:4297-305) suggested that PIK3CA mutation, found in about 15% of colorectal cancers, is a biomarker for treatment benefit from aspirin.

Such research has been prompted by the known impact of constitutive PI3K signaling on cyclooxygenase-2 (COX-2) activity and prostaglandin E2 synthesis, blocking tumor cell apoptosis, according to Dr. Kothari. By inhibiting COX-2, aspirin may restore apoptosis.

Factors that may explain the studies’ differing results include differing patient populations, more advanced-stage disease in the new study, a relatively smaller share of right-sided primaries (which are associated with poorer survival) among patients with metastases, inclusion of patients with mutations of PIK3CA in exons 9 and 20 (which have an unclear impact on outcomes), and shorter follow-up.

"At this point, we have positive as well as negative results regarding the predictive value of PIK3CA for aspirin therapy. To help resolve this issue, we will contribute this data to an individual patient meta-analysis" encompassing all three studies, Dr. Kothari said. "To further explore the validity of PIK3CA as a predictive biomarker, a prospective randomized study design should be used."

"As we move into an era of next-generation sequencing, we need to consider which somatic mutations should be studied ... As we identify more mutations in PIK3CA and put together larger patient cohorts, prospective work on aspirin as targeted therapy can begin to evaluate outcomes by mutation," she added.

In the new study, the investigators performed targeted exome sequencing of tumors from patients with stage I to IV colorectal cancer treated at the Moffitt Cancer Center and Royal Melbourne Hospital to identify the cohort with PIK3CA mutations.

The primary colorectal cancer tumor was right sided in 107 patients, left sided in 77 patients, and of unknown location in 1 patient.

With a median follow-up of 46 months, aspirin users and nonusers had statistically indistinguishable overall survival and cancer-specific survival, reported Dr. Kothari. The findings remained the same in a multivariate analysis that included potential confounders.

Furthermore, there was no benefit in terms of recurrence-free survival among patients with stage II and III disease.

There was a trend toward better overall survival for aspirin users among patients with stage IV disease in univariate analysis (hazard ratio, 0.40; P = .06) but not in multivariate analysis.

"Of note, we did find a statistically significant worsened survival with right-sided cancers in this stage IV population," Dr. Kothari pointed out (HR for left vs. right, 0.43; P = .037). "The improved survival with aspirin use seen initially in our stage IV univariate analysis might thus be due to a decrease in incidence of right-sided cancers."

Dr. Kothari disclosed no relevant conflicts of interest.

SAN FRANCISCO – Regular aspirin use did not improve outcomes among patients with colorectal cancers with mutations of the PIK3CA gene, suggest new data from the largest study yet of aspirin use in this patient population.

Regular aspirin use was reported by 26% of the 185 patients studied, researchers reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Users and nonusers were statistically indistinguishable with respect to a variety of recurrence- and survival-related outcomes, according to first author Dr. Nishi Kothari of the H. Lee Moffitt Cancer Center and Research Institute in Tampa.

"Our collaborative study did not validate overall or cancer-specific survival benefits associated with aspirin in PIK3CA-mutant patients across all stages, despite having a larger data set of patients" than earlier studies. "We were also not able to validate the recurrence-free survival benefits associated with aspirin in PIK3CA patients with stages II and III colorectal cancers."

The earlier health professionals study (N. Engl. J. Med. 2012;367:1596-606)and adjuvant VICTOR (Vioxx in Colorectal Cancer Therapy: Definition of Optimal Regime) trial (J. Clin. Oncol. 2013;31:4297-305) suggested that PIK3CA mutation, found in about 15% of colorectal cancers, is a biomarker for treatment benefit from aspirin.

Such research has been prompted by the known impact of constitutive PI3K signaling on cyclooxygenase-2 (COX-2) activity and prostaglandin E2 synthesis, blocking tumor cell apoptosis, according to Dr. Kothari. By inhibiting COX-2, aspirin may restore apoptosis.

Factors that may explain the studies’ differing results include differing patient populations, more advanced-stage disease in the new study, a relatively smaller share of right-sided primaries (which are associated with poorer survival) among patients with metastases, inclusion of patients with mutations of PIK3CA in exons 9 and 20 (which have an unclear impact on outcomes), and shorter follow-up.

"At this point, we have positive as well as negative results regarding the predictive value of PIK3CA for aspirin therapy. To help resolve this issue, we will contribute this data to an individual patient meta-analysis" encompassing all three studies, Dr. Kothari said. "To further explore the validity of PIK3CA as a predictive biomarker, a prospective randomized study design should be used."

"As we move into an era of next-generation sequencing, we need to consider which somatic mutations should be studied ... As we identify more mutations in PIK3CA and put together larger patient cohorts, prospective work on aspirin as targeted therapy can begin to evaluate outcomes by mutation," she added.

In the new study, the investigators performed targeted exome sequencing of tumors from patients with stage I to IV colorectal cancer treated at the Moffitt Cancer Center and Royal Melbourne Hospital to identify the cohort with PIK3CA mutations.

The primary colorectal cancer tumor was right sided in 107 patients, left sided in 77 patients, and of unknown location in 1 patient.

With a median follow-up of 46 months, aspirin users and nonusers had statistically indistinguishable overall survival and cancer-specific survival, reported Dr. Kothari. The findings remained the same in a multivariate analysis that included potential confounders.

Furthermore, there was no benefit in terms of recurrence-free survival among patients with stage II and III disease.

There was a trend toward better overall survival for aspirin users among patients with stage IV disease in univariate analysis (hazard ratio, 0.40; P = .06) but not in multivariate analysis.

"Of note, we did find a statistically significant worsened survival with right-sided cancers in this stage IV population," Dr. Kothari pointed out (HR for left vs. right, 0.43; P = .037). "The improved survival with aspirin use seen initially in our stage IV univariate analysis might thus be due to a decrease in incidence of right-sided cancers."

Dr. Kothari disclosed no relevant conflicts of interest.

SAN FRANCISCO – Oral capecitabine is as effective as infused 5-fluorouracil when given as part of neoadjuvant therapy for rectal cancer, new data show. Adding oxaliplatin to either regimen increases toxicity and does not improve efficacy.

These were among the mature results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-04 trial, being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

In the trial, 1,608 patients with resectable stage II or III rectal cancer received neoadjuvant chemoradiotherapy consisting of radiation plus either capecitabine or fluorouracil, each with or without oxaliplatin.

The 3-year rate of locoregional control was high overall, at almost 90%, and statistically indistinguishable between patients who received capecitabine and patients who received 5-fluorouracil (5-FU), lead study author Dr. Carmen Joseph Allegra, a professor of medicine at the University of Florida in Gainesville reported in a press briefing.

"Capecitabine with preop radiation therapy achieved rates similar to continuous infusion 5-FU for the primary endpoint of locoregional failure, as well as for pathologic complete response rate and longer-term outcomes such as disease-free survival and overall survival," Dr. Allegra commented. "This study establishes capecitabine as a standard of care in the preop rectal setting."

"Oxaliplatin did not improve outcomes but added significant toxicity, primarily in the form of diarrhea, and is therefore not indicated in combination with radiation therapy in the preop rectal therapy setting," he added.

Capecitabine has advantages over 5-FU in terms of convenience and avoidance of the need to place central venous catheters and use infusion pumps. Although capecitabine is more expensive in terms of simple drug cost, 5-FU carries the additional costs of ports and infusions.

"This study in over 1,600 patients definitively demonstrates that patients can be treated with oral capecitabine instead of continuous infusion 5-FU, giving our patients a more convenient treatment option. The study also adds to data from prior trials concluding that oxaliplatin does not improve tumor response in this setting," commented press briefing moderator Dr. Smitha Krishnamurthi of Case Western Reserve University in Cleveland.

For the R-04 trial, patients were randomly assigned to receive 5 weeks of radiation therapy. They also received either 5-FU alone; 5-FU with oxaliplatin; capecitabine alone; or capecitabine with oxaliplatin. About a month later, they underwent surgery.

Capecitabine (Xeloda) is approved by the Food and Drug Administration for the treatment of breast and colorectal cancers. Fluorouracil (Adrucil) is approved for the treatment of colorectal and multiple other cancers. Oxaliplatin (Eloxatin) is approved for the treatment of colorectal cancer.

Main results showed that the trial arms were statistically indistinguishable with respect to rates of locoregional control, which required that the patient undergo surgery, have an R0 (complete) resection, and not have any recurrence.

The 3-year values ranged from 87.9% to 88.8%, with no significant difference between the capecitabine and 5-FU groups, or between the oxaliplatin and no-oxaliplatin groups.

The rate of locoregional recurrence was about 4% overall, with values essentially the same across groups, reported Dr. Allegra, who disclosed no relevant conflicts of interest.

In the entire trial population, the 5-year rate of disease-free survival was about 65%, and the 5-year rate of overall survival was about 80%, also with statistically indistinguishable rates by group.

There was no evidence of a significant interaction between capecitabine/5-FU treatment and oxaliplatin treatment in any of the efficacy analyses.

Capecitabine and 5-FU were similar with respect to the rate of overall grade 3 or worse toxicity (30% and 27%) and grade 3 or 4 diarrhea (7% for each).

However, adding oxaliplatin to either regimen increased to 40%-42% the rate of overall grade 3 or worse toxicity and to 16% the rate of grade 3 or 4 diarrhea.

SAN FRANCISCO – Oral capecitabine is as effective as infused 5-fluorouracil when given as part of neoadjuvant therapy for rectal cancer, new data show. Adding oxaliplatin to either regimen increases toxicity and does not improve efficacy.

These were among the mature results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-04 trial, being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

In the trial, 1,608 patients with resectable stage II or III rectal cancer received neoadjuvant chemoradiotherapy consisting of radiation plus either capecitabine or fluorouracil, each with or without oxaliplatin.

The 3-year rate of locoregional control was high overall, at almost 90%, and statistically indistinguishable between patients who received capecitabine and patients who received 5-fluorouracil (5-FU), lead study author Dr. Carmen Joseph Allegra, a professor of medicine at the University of Florida in Gainesville reported in a press briefing.

"Capecitabine with preop radiation therapy achieved rates similar to continuous infusion 5-FU for the primary endpoint of locoregional failure, as well as for pathologic complete response rate and longer-term outcomes such as disease-free survival and overall survival," Dr. Allegra commented. "This study establishes capecitabine as a standard of care in the preop rectal setting."

"Oxaliplatin did not improve outcomes but added significant toxicity, primarily in the form of diarrhea, and is therefore not indicated in combination with radiation therapy in the preop rectal therapy setting," he added.

Capecitabine has advantages over 5-FU in terms of convenience and avoidance of the need to place central venous catheters and use infusion pumps. Although capecitabine is more expensive in terms of simple drug cost, 5-FU carries the additional costs of ports and infusions.

"This study in over 1,600 patients definitively demonstrates that patients can be treated with oral capecitabine instead of continuous infusion 5-FU, giving our patients a more convenient treatment option. The study also adds to data from prior trials concluding that oxaliplatin does not improve tumor response in this setting," commented press briefing moderator Dr. Smitha Krishnamurthi of Case Western Reserve University in Cleveland.

For the R-04 trial, patients were randomly assigned to receive 5 weeks of radiation therapy. They also received either 5-FU alone; 5-FU with oxaliplatin; capecitabine alone; or capecitabine with oxaliplatin. About a month later, they underwent surgery.

Capecitabine (Xeloda) is approved by the Food and Drug Administration for the treatment of breast and colorectal cancers. Fluorouracil (Adrucil) is approved for the treatment of colorectal and multiple other cancers. Oxaliplatin (Eloxatin) is approved for the treatment of colorectal cancer.

Main results showed that the trial arms were statistically indistinguishable with respect to rates of locoregional control, which required that the patient undergo surgery, have an R0 (complete) resection, and not have any recurrence.

The 3-year values ranged from 87.9% to 88.8%, with no significant difference between the capecitabine and 5-FU groups, or between the oxaliplatin and no-oxaliplatin groups.

The rate of locoregional recurrence was about 4% overall, with values essentially the same across groups, reported Dr. Allegra, who disclosed no relevant conflicts of interest.

In the entire trial population, the 5-year rate of disease-free survival was about 65%, and the 5-year rate of overall survival was about 80%, also with statistically indistinguishable rates by group.

There was no evidence of a significant interaction between capecitabine/5-FU treatment and oxaliplatin treatment in any of the efficacy analyses.

Capecitabine and 5-FU were similar with respect to the rate of overall grade 3 or worse toxicity (30% and 27%) and grade 3 or 4 diarrhea (7% for each).

However, adding oxaliplatin to either regimen increased to 40%-42% the rate of overall grade 3 or worse toxicity and to 16% the rate of grade 3 or 4 diarrhea.

SAN FRANCISCO – Oral capecitabine is as effective as infused 5-fluorouracil when given as part of neoadjuvant therapy for rectal cancer, new data show. Adding oxaliplatin to either regimen increases toxicity and does not improve efficacy.

These were among the mature results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-04 trial, being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

In the trial, 1,608 patients with resectable stage II or III rectal cancer received neoadjuvant chemoradiotherapy consisting of radiation plus either capecitabine or fluorouracil, each with or without oxaliplatin.

The 3-year rate of locoregional control was high overall, at almost 90%, and statistically indistinguishable between patients who received capecitabine and patients who received 5-fluorouracil (5-FU), lead study author Dr. Carmen Joseph Allegra, a professor of medicine at the University of Florida in Gainesville reported in a press briefing.

"Capecitabine with preop radiation therapy achieved rates similar to continuous infusion 5-FU for the primary endpoint of locoregional failure, as well as for pathologic complete response rate and longer-term outcomes such as disease-free survival and overall survival," Dr. Allegra commented. "This study establishes capecitabine as a standard of care in the preop rectal setting."

"Oxaliplatin did not improve outcomes but added significant toxicity, primarily in the form of diarrhea, and is therefore not indicated in combination with radiation therapy in the preop rectal therapy setting," he added.

Capecitabine has advantages over 5-FU in terms of convenience and avoidance of the need to place central venous catheters and use infusion pumps. Although capecitabine is more expensive in terms of simple drug cost, 5-FU carries the additional costs of ports and infusions.

"This study in over 1,600 patients definitively demonstrates that patients can be treated with oral capecitabine instead of continuous infusion 5-FU, giving our patients a more convenient treatment option. The study also adds to data from prior trials concluding that oxaliplatin does not improve tumor response in this setting," commented press briefing moderator Dr. Smitha Krishnamurthi of Case Western Reserve University in Cleveland.

For the R-04 trial, patients were randomly assigned to receive 5 weeks of radiation therapy. They also received either 5-FU alone; 5-FU with oxaliplatin; capecitabine alone; or capecitabine with oxaliplatin. About a month later, they underwent surgery.

Capecitabine (Xeloda) is approved by the Food and Drug Administration for the treatment of breast and colorectal cancers. Fluorouracil (Adrucil) is approved for the treatment of colorectal and multiple other cancers. Oxaliplatin (Eloxatin) is approved for the treatment of colorectal cancer.

Main results showed that the trial arms were statistically indistinguishable with respect to rates of locoregional control, which required that the patient undergo surgery, have an R0 (complete) resection, and not have any recurrence.

The 3-year values ranged from 87.9% to 88.8%, with no significant difference between the capecitabine and 5-FU groups, or between the oxaliplatin and no-oxaliplatin groups.

The rate of locoregional recurrence was about 4% overall, with values essentially the same across groups, reported Dr. Allegra, who disclosed no relevant conflicts of interest.

In the entire trial population, the 5-year rate of disease-free survival was about 65%, and the 5-year rate of overall survival was about 80%, also with statistically indistinguishable rates by group.

There was no evidence of a significant interaction between capecitabine/5-FU treatment and oxaliplatin treatment in any of the efficacy analyses.

Capecitabine and 5-FU were similar with respect to the rate of overall grade 3 or worse toxicity (30% and 27%) and grade 3 or 4 diarrhea (7% for each).

However, adding oxaliplatin to either regimen increased to 40%-42% the rate of overall grade 3 or worse toxicity and to 16% the rate of grade 3 or 4 diarrhea.

SAN FRANCISCO – Serial administration of two vaccines that stimulate the immune response to pancreatic cancer antigens prolonged survival of metastatic disease by about 2 months, according to Dr. Dung T. Le.

A team led by Dr. Le of the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center in Baltimore tested the vaccines – GVAX Pancreas and CRS-207 – in 90 patients.

The interim results of the phase II trial showed that overall survival was about 4 months with GVAX alone but was 6 months with GVAX followed by CRS-207, Dr. Le reported in a press briefing held before the annual Gastrointestinal Cancers Symposium. The symposium was sponsored by the American Society of Clinical Oncology.

In fact, the efficacy data met the criteria for an early halt to the trial, and patients in the single-vaccine arm are now receiving both vaccines.

"This is the first randomized study of immunotherapy in metastatic pancreatic cancer demonstrating an improvement in survival," commented press briefing moderator Dr. Smitha Krishnamurthi of Case Western Reserve University in Cleveland. "Patients who received at least one dose of the CRS-207 vaccine had a doubling of 1-year survival, and this was accomplished without the side effects of chemotherapy."

Safety results suggested that the vaccines were well tolerated. Local reactions of erythema, warmth, and swelling after intradermal administration of GVAX, as well as transient fevers and chills after infusion of CRS-207, were generally mild and transient.

"Additional clinical study of the combination treatment is underway in a three-arm study testing the combination, CRS-207 alone, and chemotherapy alone," Dr. Le noted.

GVAX is an allogeneic whole-cell vaccine. Its genetically modified pancreatic cancer cells secrete granulocyte macrophage colony-stimulating factor, which attracts dendritic cells to the vaccine site, Dr. Le explained. It is given after low-dose cyclophosphamide to inhibit a regulatory T-cell response.

CRS-207 consists of live-attenuated Listeria monocytogenes virus vaccine that expresses mesothelin. The vaccine stimulates innate and adaptive immunity to mesothelin, which is highly expressed in pancreatic cancer cells.

The investigators tested the vaccines serially in part because GVAX induces a response to a wide variety of tumor-associated antigens, and CRS-207 then boosts the response to mesothelin.

Patients in the trial, sponsored by Aduro BioTech, had declined or had experienced a failure of prior chemotherapy.

They were randomized 2:1 to receive either two doses of GVAX followed by four doses of CRS-207 or to receive six doses of GVAX therapy alone, with all doses spaced 3 weeks apart. Repeated courses were allowed as long as patients were medically stable.

With a median follow-up of 7.8 months, median overall survival among all patients who received at least one dose of vaccine was longer by nearly 2 months with dual-vaccine therapy compared with single-vaccine therapy (6.1 vs. 3.9 months; hazard ratio 0.59; P = .03).

The 1-year probability of survival was doubled with dual versus single therapy (24% vs. 12%), according to Dr. Le.

In a per-protocol analysis restricted to patients who received at least three doses of vaccine, dual therapy had a greater 5-month overall survival benefit (9.7 vs. 4.6 months; hazard ratio 0.53; P = .03).

Dr. Le disclosed no relevant financial conflicts.

SAN FRANCISCO – Serial administration of two vaccines that stimulate the immune response to pancreatic cancer antigens prolonged survival of metastatic disease by about 2 months, according to Dr. Dung T. Le.

A team led by Dr. Le of the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center in Baltimore tested the vaccines – GVAX Pancreas and CRS-207 – in 90 patients.

The interim results of the phase II trial showed that overall survival was about 4 months with GVAX alone but was 6 months with GVAX followed by CRS-207, Dr. Le reported in a press briefing held before the annual Gastrointestinal Cancers Symposium. The symposium was sponsored by the American Society of Clinical Oncology.

In fact, the efficacy data met the criteria for an early halt to the trial, and patients in the single-vaccine arm are now receiving both vaccines.

"This is the first randomized study of immunotherapy in metastatic pancreatic cancer demonstrating an improvement in survival," commented press briefing moderator Dr. Smitha Krishnamurthi of Case Western Reserve University in Cleveland. "Patients who received at least one dose of the CRS-207 vaccine had a doubling of 1-year survival, and this was accomplished without the side effects of chemotherapy."

Safety results suggested that the vaccines were well tolerated. Local reactions of erythema, warmth, and swelling after intradermal administration of GVAX, as well as transient fevers and chills after infusion of CRS-207, were generally mild and transient.

"Additional clinical study of the combination treatment is underway in a three-arm study testing the combination, CRS-207 alone, and chemotherapy alone," Dr. Le noted.

GVAX is an allogeneic whole-cell vaccine. Its genetically modified pancreatic cancer cells secrete granulocyte macrophage colony-stimulating factor, which attracts dendritic cells to the vaccine site, Dr. Le explained. It is given after low-dose cyclophosphamide to inhibit a regulatory T-cell response.

CRS-207 consists of live-attenuated Listeria monocytogenes virus vaccine that expresses mesothelin. The vaccine stimulates innate and adaptive immunity to mesothelin, which is highly expressed in pancreatic cancer cells.

The investigators tested the vaccines serially in part because GVAX induces a response to a wide variety of tumor-associated antigens, and CRS-207 then boosts the response to mesothelin.

Patients in the trial, sponsored by Aduro BioTech, had declined or had experienced a failure of prior chemotherapy.

They were randomized 2:1 to receive either two doses of GVAX followed by four doses of CRS-207 or to receive six doses of GVAX therapy alone, with all doses spaced 3 weeks apart. Repeated courses were allowed as long as patients were medically stable.

With a median follow-up of 7.8 months, median overall survival among all patients who received at least one dose of vaccine was longer by nearly 2 months with dual-vaccine therapy compared with single-vaccine therapy (6.1 vs. 3.9 months; hazard ratio 0.59; P = .03).

The 1-year probability of survival was doubled with dual versus single therapy (24% vs. 12%), according to Dr. Le.

In a per-protocol analysis restricted to patients who received at least three doses of vaccine, dual therapy had a greater 5-month overall survival benefit (9.7 vs. 4.6 months; hazard ratio 0.53; P = .03).

Dr. Le disclosed no relevant financial conflicts.

SAN FRANCISCO – Serial administration of two vaccines that stimulate the immune response to pancreatic cancer antigens prolonged survival of metastatic disease by about 2 months, according to Dr. Dung T. Le.

A team led by Dr. Le of the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center in Baltimore tested the vaccines – GVAX Pancreas and CRS-207 – in 90 patients.

The interim results of the phase II trial showed that overall survival was about 4 months with GVAX alone but was 6 months with GVAX followed by CRS-207, Dr. Le reported in a press briefing held before the annual Gastrointestinal Cancers Symposium. The symposium was sponsored by the American Society of Clinical Oncology.

In fact, the efficacy data met the criteria for an early halt to the trial, and patients in the single-vaccine arm are now receiving both vaccines.

"This is the first randomized study of immunotherapy in metastatic pancreatic cancer demonstrating an improvement in survival," commented press briefing moderator Dr. Smitha Krishnamurthi of Case Western Reserve University in Cleveland. "Patients who received at least one dose of the CRS-207 vaccine had a doubling of 1-year survival, and this was accomplished without the side effects of chemotherapy."

Safety results suggested that the vaccines were well tolerated. Local reactions of erythema, warmth, and swelling after intradermal administration of GVAX, as well as transient fevers and chills after infusion of CRS-207, were generally mild and transient.

"Additional clinical study of the combination treatment is underway in a three-arm study testing the combination, CRS-207 alone, and chemotherapy alone," Dr. Le noted.

GVAX is an allogeneic whole-cell vaccine. Its genetically modified pancreatic cancer cells secrete granulocyte macrophage colony-stimulating factor, which attracts dendritic cells to the vaccine site, Dr. Le explained. It is given after low-dose cyclophosphamide to inhibit a regulatory T-cell response.

CRS-207 consists of live-attenuated Listeria monocytogenes virus vaccine that expresses mesothelin. The vaccine stimulates innate and adaptive immunity to mesothelin, which is highly expressed in pancreatic cancer cells.

The investigators tested the vaccines serially in part because GVAX induces a response to a wide variety of tumor-associated antigens, and CRS-207 then boosts the response to mesothelin.

Patients in the trial, sponsored by Aduro BioTech, had declined or had experienced a failure of prior chemotherapy.

They were randomized 2:1 to receive either two doses of GVAX followed by four doses of CRS-207 or to receive six doses of GVAX therapy alone, with all doses spaced 3 weeks apart. Repeated courses were allowed as long as patients were medically stable.

With a median follow-up of 7.8 months, median overall survival among all patients who received at least one dose of vaccine was longer by nearly 2 months with dual-vaccine therapy compared with single-vaccine therapy (6.1 vs. 3.9 months; hazard ratio 0.59; P = .03).

The 1-year probability of survival was doubled with dual versus single therapy (24% vs. 12%), according to Dr. Le.

In a per-protocol analysis restricted to patients who received at least three doses of vaccine, dual therapy had a greater 5-month overall survival benefit (9.7 vs. 4.6 months; hazard ratio 0.53; P = .03).

Dr. Le disclosed no relevant financial conflicts.

SAN FRANCISCO – Patients with metastatic colorectal cancer should be broadly tested for RAS mutations before being treated with panitumumab, according to new data from a phase III trial.

"Patients with tumors mutated in the RAS genes are unlikely to benefit from the addition of panitumumab to FOLFIRI, similar to what was seen in the patients with only a KRAS exon 2 mutation," study investigator Dr. Marc Peeters said in a press briefing.

The investigators performed genetic testing of 597 patients who had participated in an Amgen-sponsored second-line trial and whose tumors were wild type (negative) for KRAS exon 2 mutations – about 55% of the entire trial population, he reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Almost one-fifth of the patients were found to have tumor mutations in other KRAS exons or in NRAS exons, noted Dr. Peeters, professor of oncology at Antwerp University Hospital in Edegem, Belgium.

<pamong>

The trial randomized patients to FOLFIRI alone or in combination with panitumumab (Vectibix). Vectibix is manufactured by Amgen and approved by the Food and Drug Administration for the treatment of progressive EGFR-expressing metastatic colorectal cancer.

The investigators tested the banked tumor samples for other RAS mutations – specifically mutations in KRAS exons 3 and 4 and NRAS exons 2, 3, and 4.

Results showed that adding panitumumab improved the response rate among all patients whose tumors were wild type at KRAS exon 2, compared with FOLFIRI therapy alone (35% vs. 10%, respectively). Adding panitumumab to FOLFIRI therapy in patients whose tumors were also wild type for all of the RAS mutations, compared with FOLFIRI therapy alone, garnered an even higher response rate (41% vs. 10%), Dr. Peeters reported.

Also, the previously reported lack of panitumumab efficacy on response among patients whose tumors harbored KRAS exon 2 mutations, compared with those who did not harbor the mutation (13% vs. 14%), was also evident in those whose tumors harbored mutations in any of the other RAS mutations assessed, compared those who did nor harbor the mutation (15% vs. 13%), he said.

Panitumumab had a progression-free survival benefit among all patients whose tumors were wild type for KRAS exon 2 (median, 5.9 vs. 3.9 months; hazard ratio, 0.73; P = .004), but benefit was greater among those whose tumors were also wild type for all of the RAS mutations (median, 6.4 vs. 4.4 months; HR, 0.69; P = .006).

The addition of panitumumab did not significantly improve overall survival among patients whose tumors were wild type for KRAS exon 2, but there was a trend toward improvement among patients whose tumors were also wild type for all of the other RAS mutations (median, 16.2 vs. 13.9 months; HR, 0.80; P = .077).

"These results clearly support the fact that we need RAS testing when we want to treat our patients with panitumumab in the setting of metastatic colorectal cancer," said Dr. Peeters.

The trial’s findings were similar to those of PRIME (Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy), noted press briefing moderator Dr. Smitha Krishnamurthi, associate professor at Case Western Reserve University in Cleveland.

PRIME tested the addition of panitumumab to FOLFOX in the first-line setting, and recent analyses showed that RAS mutations were a negative predictor of panitumumab benefit (N. Engl. J. Med. 2013;369:1023-34).

"These results [presented by Dr. Peeters], as well as those from the PRIME and FIRE trials ... indicate that expanded RAS testing should become the standard of care in order to best identify patients who will benefit from anti-EGFR therapy," Dr. Krishnamurthi noted.

The current trial was sponsored by Amgen. Dr. Peeters disclosed that he is a consultant/advisor to and receives honoraria and research funding from Amgen. Dr. Krishnamurthi did not report having any conflicts of interest.

This article was updated 1/27/2014.

</pamong>

SAN FRANCISCO – Patients with metastatic colorectal cancer should be broadly tested for RAS mutations before being treated with panitumumab, according to new data from a phase III trial.

"Patients with tumors mutated in the RAS genes are unlikely to benefit from the addition of panitumumab to FOLFIRI, similar to what was seen in the patients with only a KRAS exon 2 mutation," study investigator Dr. Marc Peeters said in a press briefing.

The investigators performed genetic testing of 597 patients who had participated in an Amgen-sponsored second-line trial and whose tumors were wild type (negative) for KRAS exon 2 mutations – about 55% of the entire trial population, he reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Almost one-fifth of the patients were found to have tumor mutations in other KRAS exons or in NRAS exons, noted Dr. Peeters, professor of oncology at Antwerp University Hospital in Edegem, Belgium.

<pamong>

The trial randomized patients to FOLFIRI alone or in combination with panitumumab (Vectibix). Vectibix is manufactured by Amgen and approved by the Food and Drug Administration for the treatment of progressive EGFR-expressing metastatic colorectal cancer.

The investigators tested the banked tumor samples for other RAS mutations – specifically mutations in KRAS exons 3 and 4 and NRAS exons 2, 3, and 4.

Results showed that adding panitumumab improved the response rate among all patients whose tumors were wild type at KRAS exon 2, compared with FOLFIRI therapy alone (35% vs. 10%, respectively). Adding panitumumab to FOLFIRI therapy in patients whose tumors were also wild type for all of the RAS mutations, compared with FOLFIRI therapy alone, garnered an even higher response rate (41% vs. 10%), Dr. Peeters reported.

Also, the previously reported lack of panitumumab efficacy on response among patients whose tumors harbored KRAS exon 2 mutations, compared with those who did not harbor the mutation (13% vs. 14%), was also evident in those whose tumors harbored mutations in any of the other RAS mutations assessed, compared those who did nor harbor the mutation (15% vs. 13%), he said.

Panitumumab had a progression-free survival benefit among all patients whose tumors were wild type for KRAS exon 2 (median, 5.9 vs. 3.9 months; hazard ratio, 0.73; P = .004), but benefit was greater among those whose tumors were also wild type for all of the RAS mutations (median, 6.4 vs. 4.4 months; HR, 0.69; P = .006).

The addition of panitumumab did not significantly improve overall survival among patients whose tumors were wild type for KRAS exon 2, but there was a trend toward improvement among patients whose tumors were also wild type for all of the other RAS mutations (median, 16.2 vs. 13.9 months; HR, 0.80; P = .077).

"These results clearly support the fact that we need RAS testing when we want to treat our patients with panitumumab in the setting of metastatic colorectal cancer," said Dr. Peeters.

The trial’s findings were similar to those of PRIME (Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy), noted press briefing moderator Dr. Smitha Krishnamurthi, associate professor at Case Western Reserve University in Cleveland.

PRIME tested the addition of panitumumab to FOLFOX in the first-line setting, and recent analyses showed that RAS mutations were a negative predictor of panitumumab benefit (N. Engl. J. Med. 2013;369:1023-34).

"These results [presented by Dr. Peeters], as well as those from the PRIME and FIRE trials ... indicate that expanded RAS testing should become the standard of care in order to best identify patients who will benefit from anti-EGFR therapy," Dr. Krishnamurthi noted.

The current trial was sponsored by Amgen. Dr. Peeters disclosed that he is a consultant/advisor to and receives honoraria and research funding from Amgen. Dr. Krishnamurthi did not report having any conflicts of interest.

This article was updated 1/27/2014.

</pamong>

SAN FRANCISCO – Patients with metastatic colorectal cancer should be broadly tested for RAS mutations before being treated with panitumumab, according to new data from a phase III trial.

"Patients with tumors mutated in the RAS genes are unlikely to benefit from the addition of panitumumab to FOLFIRI, similar to what was seen in the patients with only a KRAS exon 2 mutation," study investigator Dr. Marc Peeters said in a press briefing.

The investigators performed genetic testing of 597 patients who had participated in an Amgen-sponsored second-line trial and whose tumors were wild type (negative) for KRAS exon 2 mutations – about 55% of the entire trial population, he reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

Almost one-fifth of the patients were found to have tumor mutations in other KRAS exons or in NRAS exons, noted Dr. Peeters, professor of oncology at Antwerp University Hospital in Edegem, Belgium.

<pamong>

The trial randomized patients to FOLFIRI alone or in combination with panitumumab (Vectibix). Vectibix is manufactured by Amgen and approved by the Food and Drug Administration for the treatment of progressive EGFR-expressing metastatic colorectal cancer.

The investigators tested the banked tumor samples for other RAS mutations – specifically mutations in KRAS exons 3 and 4 and NRAS exons 2, 3, and 4.

Results showed that adding panitumumab improved the response rate among all patients whose tumors were wild type at KRAS exon 2, compared with FOLFIRI therapy alone (35% vs. 10%, respectively). Adding panitumumab to FOLFIRI therapy in patients whose tumors were also wild type for all of the RAS mutations, compared with FOLFIRI therapy alone, garnered an even higher response rate (41% vs. 10%), Dr. Peeters reported.

Also, the previously reported lack of panitumumab efficacy on response among patients whose tumors harbored KRAS exon 2 mutations, compared with those who did not harbor the mutation (13% vs. 14%), was also evident in those whose tumors harbored mutations in any of the other RAS mutations assessed, compared those who did nor harbor the mutation (15% vs. 13%), he said.

Panitumumab had a progression-free survival benefit among all patients whose tumors were wild type for KRAS exon 2 (median, 5.9 vs. 3.9 months; hazard ratio, 0.73; P = .004), but benefit was greater among those whose tumors were also wild type for all of the RAS mutations (median, 6.4 vs. 4.4 months; HR, 0.69; P = .006).

The addition of panitumumab did not significantly improve overall survival among patients whose tumors were wild type for KRAS exon 2, but there was a trend toward improvement among patients whose tumors were also wild type for all of the other RAS mutations (median, 16.2 vs. 13.9 months; HR, 0.80; P = .077).

"These results clearly support the fact that we need RAS testing when we want to treat our patients with panitumumab in the setting of metastatic colorectal cancer," said Dr. Peeters.

The trial’s findings were similar to those of PRIME (Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy), noted press briefing moderator Dr. Smitha Krishnamurthi, associate professor at Case Western Reserve University in Cleveland.

PRIME tested the addition of panitumumab to FOLFOX in the first-line setting, and recent analyses showed that RAS mutations were a negative predictor of panitumumab benefit (N. Engl. J. Med. 2013;369:1023-34).

"These results [presented by Dr. Peeters], as well as those from the PRIME and FIRE trials ... indicate that expanded RAS testing should become the standard of care in order to best identify patients who will benefit from anti-EGFR therapy," Dr. Krishnamurthi noted.

The current trial was sponsored by Amgen. Dr. Peeters disclosed that he is a consultant/advisor to and receives honoraria and research funding from Amgen. Dr. Krishnamurthi did not report having any conflicts of interest.

This article was updated 1/27/2014.

</pamong>

Ramucirumab is likely to expand the treatment options for advanced gastric adenocarcinoma, given new data from a randomized phase III trial being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The 665 patients in the trial, known as RAINBOW (Ramucirumab in Metastatic Gastric Adenocarcinoma), were treated in the second-line setting with paclitaxel plus either placebo or ramucirumab, an investigational targeted anti-angiogenic agent.

The main results showed that compared with adding placebo, adding ramucirumab prolonged overall survival, the trial’s primary endpoint, by more than 2 months, first author Dr. Hansjochen Wilke, director of the department of oncology, hematology, and center of palliative care at Kliniken Essen-Mitte, Germany, reported during a presscast in advance of the meeting.

Furthermore, the ramucirumab-chemotherapy combination was associated with better response rates and progression-free survival.

Certain grade 3 or worse adverse events, such as hypertension, were more common with ramucirumab, but these events were manageable.

"The results of the RAINBOW trial and the recently published REGARD [Ramucirumab Monotherapy for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma] trial" (Lancet 2014;383:31-9) – which showed the benefit of this agent when added to best supportive care, also in the second line – "clearly demonstrate that ramucirumab is an effective new drug for the treatment of patients with metastatic or locally advanced unresectable gastric cancer if they have failed prior first-line platinum- and 5-FU-based combination chemotherapy," he commented.

"This largest gastric cancer second-line trial clearly demonstrates that an effective second-line therapy improves survival in patients with metastatic and far-advanced gastric cancer, and we expect that these results and other recently published randomized trial data will lead to a situation in which more patients will now be routinely treated in the second-line treatment situation if they are fit for such treatment," he added.

In fact, the Food and Drug Administration (FDA) last year assigned ramucirumab a priority review designation as a second-line treatment for advanced gastric cancer, and is expected to release its decision sometime in 2014.

Press briefing moderator Dr. Smitha Krishnamurthi, an associate professor at Case Western Reserve University, Cleveland, noted that expanding treatment options for advanced gastric cancer remains important in the United States, even though this cancer’s incidence is low compared with that worldwide.

"We do have patients with gastric cancer here, and it is a poor-prognosis cancer in the United States, as it is throughout the world," she elaborated. "So we are excited to have what appears to be an active drug for the second-line setting that can be used instead of best supportive care, or in addition to chemotherapy for patients who can tolerate chemotherapy. We are anxiously awaiting word from the FDA about approval of ramucirumab, which is expected later this year."

Patients were eligible for the global RAINBOW trial if they had experienced progression of metastatic or unresectable locally advanced gastric or gastroesophageal junction adenocarcinoma on first-line platinum- and fluoropyrimidine-containing combination therapy. They were randomized evenly to double-blind treatment with paclitaxel plus either placebo or ramucirumab (manufactured by Eli Lilly), a monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2).

Relative to placebo, ramucirumab prolonged median overall survival (9.63 vs. 7.36 months; hazard ratio, 0.81; P = .017), Dr. Wilke reported.

"This difference of 2.3 months is an astonishingly good result in such a challenging patient population. This difference was not only statistically significant but also clinically meaningful," he commented.

Ramucirumab also prolonged progression-free survival (4.40 vs. 2.86 months; HR, 0.64; P < .0001) and nearly doubled the response rate (28% vs. 16%, P = .0001).

Tumor samples are being analyzed to identify biomarkers predicting a great likelihood of benefiting from ramucirumab, according to the investigators.

Relative to placebo, ramucirumab led to higher rates of certain grade 3 or worse adverse events, such as hypertension (15% vs. 3%), bleeding/hemorrhage (4% vs. 2%), proteinuria (1.2% vs. 0%), and gastrointestinal perforation (1.2% vs. 0%). None of the cases of hypertension or proteinuria were of grade 4 or worse.

The rate of neutropenia was also sharply higher with ramucirumab than with placebo (41% vs. 19%), but the rate of febrile neutropenia was similar.

Overall, these adverse events were generally manageable and seldom led to trial discontinuation, according to Dr. Wilke.

Dr. Wilke disclosed that he receives honoraria from Eli Lilly. The trial was sponsored by Eli Lilly.

Ramucirumab is likely to expand the treatment options for advanced gastric adenocarcinoma, given new data from a randomized phase III trial being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The 665 patients in the trial, known as RAINBOW (Ramucirumab in Metastatic Gastric Adenocarcinoma), were treated in the second-line setting with paclitaxel plus either placebo or ramucirumab, an investigational targeted anti-angiogenic agent.

The main results showed that compared with adding placebo, adding ramucirumab prolonged overall survival, the trial’s primary endpoint, by more than 2 months, first author Dr. Hansjochen Wilke, director of the department of oncology, hematology, and center of palliative care at Kliniken Essen-Mitte, Germany, reported during a presscast in advance of the meeting.

Furthermore, the ramucirumab-chemotherapy combination was associated with better response rates and progression-free survival.

Certain grade 3 or worse adverse events, such as hypertension, were more common with ramucirumab, but these events were manageable.

"The results of the RAINBOW trial and the recently published REGARD [Ramucirumab Monotherapy for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma] trial" (Lancet 2014;383:31-9) – which showed the benefit of this agent when added to best supportive care, also in the second line – "clearly demonstrate that ramucirumab is an effective new drug for the treatment of patients with metastatic or locally advanced unresectable gastric cancer if they have failed prior first-line platinum- and 5-FU-based combination chemotherapy," he commented.

"This largest gastric cancer second-line trial clearly demonstrates that an effective second-line therapy improves survival in patients with metastatic and far-advanced gastric cancer, and we expect that these results and other recently published randomized trial data will lead to a situation in which more patients will now be routinely treated in the second-line treatment situation if they are fit for such treatment," he added.

In fact, the Food and Drug Administration (FDA) last year assigned ramucirumab a priority review designation as a second-line treatment for advanced gastric cancer, and is expected to release its decision sometime in 2014.

Press briefing moderator Dr. Smitha Krishnamurthi, an associate professor at Case Western Reserve University, Cleveland, noted that expanding treatment options for advanced gastric cancer remains important in the United States, even though this cancer’s incidence is low compared with that worldwide.

"We do have patients with gastric cancer here, and it is a poor-prognosis cancer in the United States, as it is throughout the world," she elaborated. "So we are excited to have what appears to be an active drug for the second-line setting that can be used instead of best supportive care, or in addition to chemotherapy for patients who can tolerate chemotherapy. We are anxiously awaiting word from the FDA about approval of ramucirumab, which is expected later this year."

Patients were eligible for the global RAINBOW trial if they had experienced progression of metastatic or unresectable locally advanced gastric or gastroesophageal junction adenocarcinoma on first-line platinum- and fluoropyrimidine-containing combination therapy. They were randomized evenly to double-blind treatment with paclitaxel plus either placebo or ramucirumab (manufactured by Eli Lilly), a monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2).

Relative to placebo, ramucirumab prolonged median overall survival (9.63 vs. 7.36 months; hazard ratio, 0.81; P = .017), Dr. Wilke reported.

"This difference of 2.3 months is an astonishingly good result in such a challenging patient population. This difference was not only statistically significant but also clinically meaningful," he commented.

Ramucirumab also prolonged progression-free survival (4.40 vs. 2.86 months; HR, 0.64; P < .0001) and nearly doubled the response rate (28% vs. 16%, P = .0001).

Tumor samples are being analyzed to identify biomarkers predicting a great likelihood of benefiting from ramucirumab, according to the investigators.

Relative to placebo, ramucirumab led to higher rates of certain grade 3 or worse adverse events, such as hypertension (15% vs. 3%), bleeding/hemorrhage (4% vs. 2%), proteinuria (1.2% vs. 0%), and gastrointestinal perforation (1.2% vs. 0%). None of the cases of hypertension or proteinuria were of grade 4 or worse.

The rate of neutropenia was also sharply higher with ramucirumab than with placebo (41% vs. 19%), but the rate of febrile neutropenia was similar.

Overall, these adverse events were generally manageable and seldom led to trial discontinuation, according to Dr. Wilke.

Dr. Wilke disclosed that he receives honoraria from Eli Lilly. The trial was sponsored by Eli Lilly.

Ramucirumab is likely to expand the treatment options for advanced gastric adenocarcinoma, given new data from a randomized phase III trial being reported at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The 665 patients in the trial, known as RAINBOW (Ramucirumab in Metastatic Gastric Adenocarcinoma), were treated in the second-line setting with paclitaxel plus either placebo or ramucirumab, an investigational targeted anti-angiogenic agent.

The main results showed that compared with adding placebo, adding ramucirumab prolonged overall survival, the trial’s primary endpoint, by more than 2 months, first author Dr. Hansjochen Wilke, director of the department of oncology, hematology, and center of palliative care at Kliniken Essen-Mitte, Germany, reported during a presscast in advance of the meeting.

Furthermore, the ramucirumab-chemotherapy combination was associated with better response rates and progression-free survival.

Certain grade 3 or worse adverse events, such as hypertension, were more common with ramucirumab, but these events were manageable.

"The results of the RAINBOW trial and the recently published REGARD [Ramucirumab Monotherapy for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma] trial" (Lancet 2014;383:31-9) – which showed the benefit of this agent when added to best supportive care, also in the second line – "clearly demonstrate that ramucirumab is an effective new drug for the treatment of patients with metastatic or locally advanced unresectable gastric cancer if they have failed prior first-line platinum- and 5-FU-based combination chemotherapy," he commented.

"This largest gastric cancer second-line trial clearly demonstrates that an effective second-line therapy improves survival in patients with metastatic and far-advanced gastric cancer, and we expect that these results and other recently published randomized trial data will lead to a situation in which more patients will now be routinely treated in the second-line treatment situation if they are fit for such treatment," he added.

In fact, the Food and Drug Administration (FDA) last year assigned ramucirumab a priority review designation as a second-line treatment for advanced gastric cancer, and is expected to release its decision sometime in 2014.

Press briefing moderator Dr. Smitha Krishnamurthi, an associate professor at Case Western Reserve University, Cleveland, noted that expanding treatment options for advanced gastric cancer remains important in the United States, even though this cancer’s incidence is low compared with that worldwide.

"We do have patients with gastric cancer here, and it is a poor-prognosis cancer in the United States, as it is throughout the world," she elaborated. "So we are excited to have what appears to be an active drug for the second-line setting that can be used instead of best supportive care, or in addition to chemotherapy for patients who can tolerate chemotherapy. We are anxiously awaiting word from the FDA about approval of ramucirumab, which is expected later this year."

Patients were eligible for the global RAINBOW trial if they had experienced progression of metastatic or unresectable locally advanced gastric or gastroesophageal junction adenocarcinoma on first-line platinum- and fluoropyrimidine-containing combination therapy. They were randomized evenly to double-blind treatment with paclitaxel plus either placebo or ramucirumab (manufactured by Eli Lilly), a monoclonal antibody to vascular endothelial growth factor receptor 2 (VEGFR-2).

Relative to placebo, ramucirumab prolonged median overall survival (9.63 vs. 7.36 months; hazard ratio, 0.81; P = .017), Dr. Wilke reported.

"This difference of 2.3 months is an astonishingly good result in such a challenging patient population. This difference was not only statistically significant but also clinically meaningful," he commented.

Ramucirumab also prolonged progression-free survival (4.40 vs. 2.86 months; HR, 0.64; P < .0001) and nearly doubled the response rate (28% vs. 16%, P = .0001).

Tumor samples are being analyzed to identify biomarkers predicting a great likelihood of benefiting from ramucirumab, according to the investigators.

Relative to placebo, ramucirumab led to higher rates of certain grade 3 or worse adverse events, such as hypertension (15% vs. 3%), bleeding/hemorrhage (4% vs. 2%), proteinuria (1.2% vs. 0%), and gastrointestinal perforation (1.2% vs. 0%). None of the cases of hypertension or proteinuria were of grade 4 or worse.

The rate of neutropenia was also sharply higher with ramucirumab than with placebo (41% vs. 19%), but the rate of febrile neutropenia was similar.

Overall, these adverse events were generally manageable and seldom led to trial discontinuation, according to Dr. Wilke.

Dr. Wilke disclosed that he receives honoraria from Eli Lilly. The trial was sponsored by Eli Lilly.