Susan London

SAN FRANCISCO – An investigational immunomodulator, IMM-101, improves outcomes in patients who have advanced pancreatic cancer when combined with chemotherapy, with minimal increase in toxicity, suggest data from an open-label, phase II trial conducted in Europe.

Results reported in a poster session at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology showed that median progression-free survival was about 1 month longer for patients given IMM-101 plus gemcitabine than for patients given gemcitabine alone; the gain exceeded 2 months among the subgroup having metastatic disease. The combination was associated with slightly higher rates of certain toxicities that seemed to stem from being on gemcitabine for longer.

Susan London/Frontline Medical News

“I think IMM-101 brings to the field something that’s missing,” lead investigator Dr. Angus G. Dalgleish, a professor and medical oncologist at St. George’s University of London, commented in an interview. “Everybody has been doing doublets, triplets, etcetera. All they do is guarantee increased toxicity and, in some cases, misery to the patient, whereas this allows you to start treatment and stabilize [the cancer].”

“This shows that actually boosting the immune response in a nonspecific manner before we do anything else may well become the gold standard when you add in any other treatment,” he added. “And I think it’s a non–chemo specific thing and a non–tumor specific thing, because we have done all the preliminary work in melanoma. We’ve also got very encouraging data in prostate and are starting prostate studies this year. And I would like to see it go into a whole host of ones where chemo needs a nonspecific boost, like ovarian [cancer].”

Of note, the trial opened just before FOLFIRINOX (irinotecan plus 5-fluorouracil plus leucovorin plus oxaliplatin) became available to patients in Europe, and many of the more fit eligible patients opted for that therapy instead. “I think this makes the survival benefit even more remarkable,” Dr. Dalgleish stated.

IMM-101 is a heat-killed whole-cell vaccine that is given intradermally and induces protective CD8 T-cell responses. “Although we had good data on this agent for melanoma, we noticed that it sort of boosted the immune system in all cancers [in which] we could show you get immune suppression,” he noted. Additionally, preclinical data hinted at synergy with gemcitabine.

The trial, known as IMAGE 1 (Immune Modulation And Gemcitabine Evaluation 1) and sponsored by manufacturer Immodulon Therapeutics, enrolled 110 patients with stage III or IV pancreatic cancer who had not previously received any chemotherapy. The patients were randomized 2:1 to receive gemcitabine (Gemzar) either with or without IMM-101.

Intention-to-treat analyses showed that median overall survival, the primary endpoint, was 6.7 months with IMM-101 and 5.6 months without it in the entire trial population (hazard ratio, 0.68; P = .075). The difference was significant among the subset of patients having metastatic disease (7.0 vs. 4.4 months; HR, 0.54; P = .010).

“You are getting a quick effect here, 2-4 months,” Dr. Dalgleish pointed out. “I’ve done several vaccine studies where we don’t even get the split [in survival curves] for 12 months. ... So that’s absolutely staggering that we get the split so early on.”

“In the metastatic group, the survival advantage is really quite dramatic,” he added. “And unlike many other studies that we have been involved in, you are getting this tail. ... these patients are still continuing to survive.”

One patient given the combination experienced progression and was then given nab-paclitaxel (Abraxane), and had a complete response to that agent, according to Dr. Dalgleish. He speculated that it may have been due to the immune priming by IMM-101.

In per protocol analyses, the survival benefit was significant in both the entire population and the patients with metastatic disease.

Patients in the IMM-101 group also had superior progression-free survival, seen in the entire trial population (4.4 vs. 2.4 months; HR, 0.51; P = .003) and in the subgroup with metastases (4.4 vs. 2.3 months; HR, 0.40; P less than .001).

Apart from injection site reactions in some patients, IMM-101 was well tolerated, according to Dr. Dalgleish.

“When you add gemcitabine plus ‘x’ – Iressa [gefitinib], capecitabine [Xeloda], Abraxane, etcetera – you get a benefit but at great cost,” he commented. In this trial, toxicity “is slightly worse in the combination arm, but the side effects are all those associated with the chemotherapy and the disease – nothing to do with the immune modulator, which we have given to hundreds of patients before. And that would appear to reflect the fact that those patients have been on gemcitabine for longer than the ones on gemcitabine alone.”

Quality of life data are still being analyzed, according to Dr. Dalgleish. “But ... from my personal experience, the patients do feel better on the vaccine as [it has] a kind of overall boosting effect.”

The investigators plan to take IMM-101 forward in clinical trials, he said. “But I think in the States, they might want to do that with Abraxane first line.” In the United Kingdom, the National Institute for Health and Care Excellence (NICE) recently declined Abraxane, meaning cost won’t be reimbursed if it is used, Dr. Dalgleish said. “So we may well be able to do the same study in Europe in order to get approval, although personally, I’d be very keen for conditional approval on this [trial] in the U.K. because it has a clear benefit without any toxicity. And there is a system where you can get a phase 4 approval and have postapproval monitoring.”

Dr. Dalgleish disclosed that he has a consulting or advisory role with and receives research funding from Immodulon Therapeutics.

SAN FRANCISCO – An investigational immunomodulator, IMM-101, improves outcomes in patients who have advanced pancreatic cancer when combined with chemotherapy, with minimal increase in toxicity, suggest data from an open-label, phase II trial conducted in Europe.

Results reported in a poster session at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology showed that median progression-free survival was about 1 month longer for patients given IMM-101 plus gemcitabine than for patients given gemcitabine alone; the gain exceeded 2 months among the subgroup having metastatic disease. The combination was associated with slightly higher rates of certain toxicities that seemed to stem from being on gemcitabine for longer.

Susan London/Frontline Medical News

“I think IMM-101 brings to the field something that’s missing,” lead investigator Dr. Angus G. Dalgleish, a professor and medical oncologist at St. George’s University of London, commented in an interview. “Everybody has been doing doublets, triplets, etcetera. All they do is guarantee increased toxicity and, in some cases, misery to the patient, whereas this allows you to start treatment and stabilize [the cancer].”

“This shows that actually boosting the immune response in a nonspecific manner before we do anything else may well become the gold standard when you add in any other treatment,” he added. “And I think it’s a non–chemo specific thing and a non–tumor specific thing, because we have done all the preliminary work in melanoma. We’ve also got very encouraging data in prostate and are starting prostate studies this year. And I would like to see it go into a whole host of ones where chemo needs a nonspecific boost, like ovarian [cancer].”

Of note, the trial opened just before FOLFIRINOX (irinotecan plus 5-fluorouracil plus leucovorin plus oxaliplatin) became available to patients in Europe, and many of the more fit eligible patients opted for that therapy instead. “I think this makes the survival benefit even more remarkable,” Dr. Dalgleish stated.

IMM-101 is a heat-killed whole-cell vaccine that is given intradermally and induces protective CD8 T-cell responses. “Although we had good data on this agent for melanoma, we noticed that it sort of boosted the immune system in all cancers [in which] we could show you get immune suppression,” he noted. Additionally, preclinical data hinted at synergy with gemcitabine.

The trial, known as IMAGE 1 (Immune Modulation And Gemcitabine Evaluation 1) and sponsored by manufacturer Immodulon Therapeutics, enrolled 110 patients with stage III or IV pancreatic cancer who had not previously received any chemotherapy. The patients were randomized 2:1 to receive gemcitabine (Gemzar) either with or without IMM-101.

Intention-to-treat analyses showed that median overall survival, the primary endpoint, was 6.7 months with IMM-101 and 5.6 months without it in the entire trial population (hazard ratio, 0.68; P = .075). The difference was significant among the subset of patients having metastatic disease (7.0 vs. 4.4 months; HR, 0.54; P = .010).

“You are getting a quick effect here, 2-4 months,” Dr. Dalgleish pointed out. “I’ve done several vaccine studies where we don’t even get the split [in survival curves] for 12 months. ... So that’s absolutely staggering that we get the split so early on.”

“In the metastatic group, the survival advantage is really quite dramatic,” he added. “And unlike many other studies that we have been involved in, you are getting this tail. ... these patients are still continuing to survive.”

One patient given the combination experienced progression and was then given nab-paclitaxel (Abraxane), and had a complete response to that agent, according to Dr. Dalgleish. He speculated that it may have been due to the immune priming by IMM-101.

In per protocol analyses, the survival benefit was significant in both the entire population and the patients with metastatic disease.

Patients in the IMM-101 group also had superior progression-free survival, seen in the entire trial population (4.4 vs. 2.4 months; HR, 0.51; P = .003) and in the subgroup with metastases (4.4 vs. 2.3 months; HR, 0.40; P less than .001).

Apart from injection site reactions in some patients, IMM-101 was well tolerated, according to Dr. Dalgleish.

“When you add gemcitabine plus ‘x’ – Iressa [gefitinib], capecitabine [Xeloda], Abraxane, etcetera – you get a benefit but at great cost,” he commented. In this trial, toxicity “is slightly worse in the combination arm, but the side effects are all those associated with the chemotherapy and the disease – nothing to do with the immune modulator, which we have given to hundreds of patients before. And that would appear to reflect the fact that those patients have been on gemcitabine for longer than the ones on gemcitabine alone.”

Quality of life data are still being analyzed, according to Dr. Dalgleish. “But ... from my personal experience, the patients do feel better on the vaccine as [it has] a kind of overall boosting effect.”

The investigators plan to take IMM-101 forward in clinical trials, he said. “But I think in the States, they might want to do that with Abraxane first line.” In the United Kingdom, the National Institute for Health and Care Excellence (NICE) recently declined Abraxane, meaning cost won’t be reimbursed if it is used, Dr. Dalgleish said. “So we may well be able to do the same study in Europe in order to get approval, although personally, I’d be very keen for conditional approval on this [trial] in the U.K. because it has a clear benefit without any toxicity. And there is a system where you can get a phase 4 approval and have postapproval monitoring.”

Dr. Dalgleish disclosed that he has a consulting or advisory role with and receives research funding from Immodulon Therapeutics.

SAN FRANCISCO – An investigational immunomodulator, IMM-101, improves outcomes in patients who have advanced pancreatic cancer when combined with chemotherapy, with minimal increase in toxicity, suggest data from an open-label, phase II trial conducted in Europe.

Results reported in a poster session at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology showed that median progression-free survival was about 1 month longer for patients given IMM-101 plus gemcitabine than for patients given gemcitabine alone; the gain exceeded 2 months among the subgroup having metastatic disease. The combination was associated with slightly higher rates of certain toxicities that seemed to stem from being on gemcitabine for longer.

Susan London/Frontline Medical News

“I think IMM-101 brings to the field something that’s missing,” lead investigator Dr. Angus G. Dalgleish, a professor and medical oncologist at St. George’s University of London, commented in an interview. “Everybody has been doing doublets, triplets, etcetera. All they do is guarantee increased toxicity and, in some cases, misery to the patient, whereas this allows you to start treatment and stabilize [the cancer].”

“This shows that actually boosting the immune response in a nonspecific manner before we do anything else may well become the gold standard when you add in any other treatment,” he added. “And I think it’s a non–chemo specific thing and a non–tumor specific thing, because we have done all the preliminary work in melanoma. We’ve also got very encouraging data in prostate and are starting prostate studies this year. And I would like to see it go into a whole host of ones where chemo needs a nonspecific boost, like ovarian [cancer].”

Of note, the trial opened just before FOLFIRINOX (irinotecan plus 5-fluorouracil plus leucovorin plus oxaliplatin) became available to patients in Europe, and many of the more fit eligible patients opted for that therapy instead. “I think this makes the survival benefit even more remarkable,” Dr. Dalgleish stated.

IMM-101 is a heat-killed whole-cell vaccine that is given intradermally and induces protective CD8 T-cell responses. “Although we had good data on this agent for melanoma, we noticed that it sort of boosted the immune system in all cancers [in which] we could show you get immune suppression,” he noted. Additionally, preclinical data hinted at synergy with gemcitabine.

The trial, known as IMAGE 1 (Immune Modulation And Gemcitabine Evaluation 1) and sponsored by manufacturer Immodulon Therapeutics, enrolled 110 patients with stage III or IV pancreatic cancer who had not previously received any chemotherapy. The patients were randomized 2:1 to receive gemcitabine (Gemzar) either with or without IMM-101.

Intention-to-treat analyses showed that median overall survival, the primary endpoint, was 6.7 months with IMM-101 and 5.6 months without it in the entire trial population (hazard ratio, 0.68; P = .075). The difference was significant among the subset of patients having metastatic disease (7.0 vs. 4.4 months; HR, 0.54; P = .010).

“You are getting a quick effect here, 2-4 months,” Dr. Dalgleish pointed out. “I’ve done several vaccine studies where we don’t even get the split [in survival curves] for 12 months. ... So that’s absolutely staggering that we get the split so early on.”

“In the metastatic group, the survival advantage is really quite dramatic,” he added. “And unlike many other studies that we have been involved in, you are getting this tail. ... these patients are still continuing to survive.”

One patient given the combination experienced progression and was then given nab-paclitaxel (Abraxane), and had a complete response to that agent, according to Dr. Dalgleish. He speculated that it may have been due to the immune priming by IMM-101.

In per protocol analyses, the survival benefit was significant in both the entire population and the patients with metastatic disease.

Patients in the IMM-101 group also had superior progression-free survival, seen in the entire trial population (4.4 vs. 2.4 months; HR, 0.51; P = .003) and in the subgroup with metastases (4.4 vs. 2.3 months; HR, 0.40; P less than .001).

Apart from injection site reactions in some patients, IMM-101 was well tolerated, according to Dr. Dalgleish.

“When you add gemcitabine plus ‘x’ – Iressa [gefitinib], capecitabine [Xeloda], Abraxane, etcetera – you get a benefit but at great cost,” he commented. In this trial, toxicity “is slightly worse in the combination arm, but the side effects are all those associated with the chemotherapy and the disease – nothing to do with the immune modulator, which we have given to hundreds of patients before. And that would appear to reflect the fact that those patients have been on gemcitabine for longer than the ones on gemcitabine alone.”

Quality of life data are still being analyzed, according to Dr. Dalgleish. “But ... from my personal experience, the patients do feel better on the vaccine as [it has] a kind of overall boosting effect.”

The investigators plan to take IMM-101 forward in clinical trials, he said. “But I think in the States, they might want to do that with Abraxane first line.” In the United Kingdom, the National Institute for Health and Care Excellence (NICE) recently declined Abraxane, meaning cost won’t be reimbursed if it is used, Dr. Dalgleish said. “So we may well be able to do the same study in Europe in order to get approval, although personally, I’d be very keen for conditional approval on this [trial] in the U.K. because it has a clear benefit without any toxicity. And there is a system where you can get a phase 4 approval and have postapproval monitoring.”

Dr. Dalgleish disclosed that he has a consulting or advisory role with and receives research funding from Immodulon Therapeutics.

SAN FRANCISCO – The efficacy and safety of the antiangiogenic antibody ramucirumab in older patients with advanced esophagogastric cancers are similar to those seen in younger peers, a subgroup analysis of the phase III RAINBOW trial showed.

The trial tested ramucirumab (Cyramza) against placebo, each combined with paclitaxel, as second-line therapy among 665 patients with locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma. The antibody targets vascular endothelial growth factor receptor–2 (VEGFR-2) and is approved by the U.S. Food and Drug Administration for the treatment of esophagogastric cancers, as well as non–small cell lung cancer.

Overall, 37% of the patients studied were aged 65 years or older, according to data reported in a poster session at the at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The results showed that with the addition of ramucirumab versus placebo, these older patients had a 2.0-month overall survival gain that was similar to the 2.2-month survival gain seen in younger patients. The safety profile with added ramucirumab was much the same as well, except that grade 3 or higher neutropenia was more common among the older group.

“We saw very similar results” by age group, lead investigator Dr. Kei Muro, an oncologist at the Aichi Cancer Center Hospital in Nagoya, Japan, said in an interview. “Neutropenia is relatively higher in [the older group] and careful management is needed, but very similar efficacy and manageable toxicity were shown in this trial.”

The older patients in the trial, which was sponsored by manufacturer Eli Lilly, were fairly healthy other than having cancer, meeting eligibility criteria such as good performance status and adequate organ function, he said. Thus, they may not necessarily reflect patients seen in routine care.

“Ramucirumab for gastric cancer is feasible and effective in the second-line setting of advanced gastric cancer,” Dr. Muro concluded. “Ramucirumab use in all ages in the second-line setting for gastric cancer can be recommended.”

Intention-to-treat analyses showed that relative to placebo, ramucirumab prolonged median overall survival similarly among patients aged 65 years and older (10.7 vs. 8.7 months; hazard ratio, 0.86; P = .34) and among younger patients (9.3 vs. 7.1 months; HR, 0.75; P = .01).

Findings were much the same for median progression-free survival, with a benefit seen in the older age group (4.6 vs. 2.9 months; HR, 0.67; P = .0066) roughly matching that in the younger one (4.3 vs. 2.8 months; HR, 0.57; P less than .0001), reported Dr. Muro, who disclosed that he receives research funding from Eli Lilly, as well as Bristol-Myers Squibb and Merck.

Relative to placebo, ramucirumab was associated with a higher rate of grade 3 or worse neutropenia in both age groups. Among patients aged 65 years or older, the rate was 49% with the drug versus 24% with placebo; among younger patients, it was 36% and 16%, respectively.

In the ramucirumab group, the rates of most grade 3 or worse adverse events possibly related to VEGF inhibition, such as bleeding and proteinuria, were generally similar for the two age groups. Hypertension of these grades was seen in 19% of the older group, compared with 12% of the younger one.

SAN FRANCISCO – The efficacy and safety of the antiangiogenic antibody ramucirumab in older patients with advanced esophagogastric cancers are similar to those seen in younger peers, a subgroup analysis of the phase III RAINBOW trial showed.

The trial tested ramucirumab (Cyramza) against placebo, each combined with paclitaxel, as second-line therapy among 665 patients with locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma. The antibody targets vascular endothelial growth factor receptor–2 (VEGFR-2) and is approved by the U.S. Food and Drug Administration for the treatment of esophagogastric cancers, as well as non–small cell lung cancer.

Overall, 37% of the patients studied were aged 65 years or older, according to data reported in a poster session at the at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The results showed that with the addition of ramucirumab versus placebo, these older patients had a 2.0-month overall survival gain that was similar to the 2.2-month survival gain seen in younger patients. The safety profile with added ramucirumab was much the same as well, except that grade 3 or higher neutropenia was more common among the older group.

“We saw very similar results” by age group, lead investigator Dr. Kei Muro, an oncologist at the Aichi Cancer Center Hospital in Nagoya, Japan, said in an interview. “Neutropenia is relatively higher in [the older group] and careful management is needed, but very similar efficacy and manageable toxicity were shown in this trial.”

The older patients in the trial, which was sponsored by manufacturer Eli Lilly, were fairly healthy other than having cancer, meeting eligibility criteria such as good performance status and adequate organ function, he said. Thus, they may not necessarily reflect patients seen in routine care.

“Ramucirumab for gastric cancer is feasible and effective in the second-line setting of advanced gastric cancer,” Dr. Muro concluded. “Ramucirumab use in all ages in the second-line setting for gastric cancer can be recommended.”

Intention-to-treat analyses showed that relative to placebo, ramucirumab prolonged median overall survival similarly among patients aged 65 years and older (10.7 vs. 8.7 months; hazard ratio, 0.86; P = .34) and among younger patients (9.3 vs. 7.1 months; HR, 0.75; P = .01).

Findings were much the same for median progression-free survival, with a benefit seen in the older age group (4.6 vs. 2.9 months; HR, 0.67; P = .0066) roughly matching that in the younger one (4.3 vs. 2.8 months; HR, 0.57; P less than .0001), reported Dr. Muro, who disclosed that he receives research funding from Eli Lilly, as well as Bristol-Myers Squibb and Merck.

Relative to placebo, ramucirumab was associated with a higher rate of grade 3 or worse neutropenia in both age groups. Among patients aged 65 years or older, the rate was 49% with the drug versus 24% with placebo; among younger patients, it was 36% and 16%, respectively.

In the ramucirumab group, the rates of most grade 3 or worse adverse events possibly related to VEGF inhibition, such as bleeding and proteinuria, were generally similar for the two age groups. Hypertension of these grades was seen in 19% of the older group, compared with 12% of the younger one.

SAN FRANCISCO – The efficacy and safety of the antiangiogenic antibody ramucirumab in older patients with advanced esophagogastric cancers are similar to those seen in younger peers, a subgroup analysis of the phase III RAINBOW trial showed.

The trial tested ramucirumab (Cyramza) against placebo, each combined with paclitaxel, as second-line therapy among 665 patients with locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma. The antibody targets vascular endothelial growth factor receptor–2 (VEGFR-2) and is approved by the U.S. Food and Drug Administration for the treatment of esophagogastric cancers, as well as non–small cell lung cancer.

Overall, 37% of the patients studied were aged 65 years or older, according to data reported in a poster session at the at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The results showed that with the addition of ramucirumab versus placebo, these older patients had a 2.0-month overall survival gain that was similar to the 2.2-month survival gain seen in younger patients. The safety profile with added ramucirumab was much the same as well, except that grade 3 or higher neutropenia was more common among the older group.

“We saw very similar results” by age group, lead investigator Dr. Kei Muro, an oncologist at the Aichi Cancer Center Hospital in Nagoya, Japan, said in an interview. “Neutropenia is relatively higher in [the older group] and careful management is needed, but very similar efficacy and manageable toxicity were shown in this trial.”

The older patients in the trial, which was sponsored by manufacturer Eli Lilly, were fairly healthy other than having cancer, meeting eligibility criteria such as good performance status and adequate organ function, he said. Thus, they may not necessarily reflect patients seen in routine care.

“Ramucirumab for gastric cancer is feasible and effective in the second-line setting of advanced gastric cancer,” Dr. Muro concluded. “Ramucirumab use in all ages in the second-line setting for gastric cancer can be recommended.”

Intention-to-treat analyses showed that relative to placebo, ramucirumab prolonged median overall survival similarly among patients aged 65 years and older (10.7 vs. 8.7 months; hazard ratio, 0.86; P = .34) and among younger patients (9.3 vs. 7.1 months; HR, 0.75; P = .01).

Findings were much the same for median progression-free survival, with a benefit seen in the older age group (4.6 vs. 2.9 months; HR, 0.67; P = .0066) roughly matching that in the younger one (4.3 vs. 2.8 months; HR, 0.57; P less than .0001), reported Dr. Muro, who disclosed that he receives research funding from Eli Lilly, as well as Bristol-Myers Squibb and Merck.

Relative to placebo, ramucirumab was associated with a higher rate of grade 3 or worse neutropenia in both age groups. Among patients aged 65 years or older, the rate was 49% with the drug versus 24% with placebo; among younger patients, it was 36% and 16%, respectively.

In the ramucirumab group, the rates of most grade 3 or worse adverse events possibly related to VEGF inhibition, such as bleeding and proteinuria, were generally similar for the two age groups. Hypertension of these grades was seen in 19% of the older group, compared with 12% of the younger one.

SAN FRANCISCO – Survival benefits seen with first-line therapy for metastatic colorectal cancer in clinical trials have limited generalizability to patients treated in real-world practice, suggests a study reported at the 2015 Gastrointestinal Cancers Symposium.

Investigators compared 16,614 patients from 31 randomized phase III trials of first-line therapy published between 2005 and 2010 with similar matched patients from the Surveillance, Epidemiology, and End Results (SEER) database.

Findings showed that the patients on trials as a whole had a median overall survival of 18.9 months and 1- and 2-year overall survival rates of 70% and 36%, respectively, Ziwei Wang reported in a poster session.

Relative to their real-world counterparts, trial patients had better median overall survival in 95% of trial arms (average difference, 5.4 months), better 1-year overall survival in 94% of trial arms (average difference, 16.7%), and better 2-year overall survival in 71% of trial arms (average difference, 7.2%) (P less than .0001 for each).

“When patients go to their physicians, they want to know what’s the prognosis, what benefit does the drug that you are giving me translate into, how does that help my overall survival,” Ms. Wang commented in an interview. “And most physicians get their information just from the clinical trial data that comes out.”

Taken together, the study’s findings are “a good message to physicians just to be mindful that these differences do exist and not to just draw from clinical trials to inform your patients,” she said. “You can sort of think about what you are telling them to let them know that the information you are giving them is coming from trials that might not be reflective of what we see in the general population.”

The survival gaps likely stem in part from the often-strict eligibility criteria used in clinical trials, according to Ms. Wang, who is a medical student at the University of California, San Diego.

“When you are designing clinical trials, you have a set of criteria that a patient has to meet before they are even allowed to enroll, so already, you might kind of be drawing from an unrepresentative sample when you start these trials,” she elaborated. “And so we think that a lot of that plays into why you see these differences between what the trial concludes and what SEER shows.”

A previous similar study compared survival among patients with a variety of cancers treated in versus out of clinical trials (J. Natl. Cancer Inst. 2014 [doi:10.1093/jnci/dju002]), Ms. Wang noted at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“They found that initially, the clinical trial patients did better, but after 5 years or so, it kind of evened out,” she said. “What we found was up until 5 years and even longer, you do see a difference.”

SAN FRANCISCO – Survival benefits seen with first-line therapy for metastatic colorectal cancer in clinical trials have limited generalizability to patients treated in real-world practice, suggests a study reported at the 2015 Gastrointestinal Cancers Symposium.

Investigators compared 16,614 patients from 31 randomized phase III trials of first-line therapy published between 2005 and 2010 with similar matched patients from the Surveillance, Epidemiology, and End Results (SEER) database.

Findings showed that the patients on trials as a whole had a median overall survival of 18.9 months and 1- and 2-year overall survival rates of 70% and 36%, respectively, Ziwei Wang reported in a poster session.

Relative to their real-world counterparts, trial patients had better median overall survival in 95% of trial arms (average difference, 5.4 months), better 1-year overall survival in 94% of trial arms (average difference, 16.7%), and better 2-year overall survival in 71% of trial arms (average difference, 7.2%) (P less than .0001 for each).

“When patients go to their physicians, they want to know what’s the prognosis, what benefit does the drug that you are giving me translate into, how does that help my overall survival,” Ms. Wang commented in an interview. “And most physicians get their information just from the clinical trial data that comes out.”

Taken together, the study’s findings are “a good message to physicians just to be mindful that these differences do exist and not to just draw from clinical trials to inform your patients,” she said. “You can sort of think about what you are telling them to let them know that the information you are giving them is coming from trials that might not be reflective of what we see in the general population.”

The survival gaps likely stem in part from the often-strict eligibility criteria used in clinical trials, according to Ms. Wang, who is a medical student at the University of California, San Diego.

“When you are designing clinical trials, you have a set of criteria that a patient has to meet before they are even allowed to enroll, so already, you might kind of be drawing from an unrepresentative sample when you start these trials,” she elaborated. “And so we think that a lot of that plays into why you see these differences between what the trial concludes and what SEER shows.”

A previous similar study compared survival among patients with a variety of cancers treated in versus out of clinical trials (J. Natl. Cancer Inst. 2014 [doi:10.1093/jnci/dju002]), Ms. Wang noted at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“They found that initially, the clinical trial patients did better, but after 5 years or so, it kind of evened out,” she said. “What we found was up until 5 years and even longer, you do see a difference.”

SAN FRANCISCO – Survival benefits seen with first-line therapy for metastatic colorectal cancer in clinical trials have limited generalizability to patients treated in real-world practice, suggests a study reported at the 2015 Gastrointestinal Cancers Symposium.

Investigators compared 16,614 patients from 31 randomized phase III trials of first-line therapy published between 2005 and 2010 with similar matched patients from the Surveillance, Epidemiology, and End Results (SEER) database.

Findings showed that the patients on trials as a whole had a median overall survival of 18.9 months and 1- and 2-year overall survival rates of 70% and 36%, respectively, Ziwei Wang reported in a poster session.

Relative to their real-world counterparts, trial patients had better median overall survival in 95% of trial arms (average difference, 5.4 months), better 1-year overall survival in 94% of trial arms (average difference, 16.7%), and better 2-year overall survival in 71% of trial arms (average difference, 7.2%) (P less than .0001 for each).

“When patients go to their physicians, they want to know what’s the prognosis, what benefit does the drug that you are giving me translate into, how does that help my overall survival,” Ms. Wang commented in an interview. “And most physicians get their information just from the clinical trial data that comes out.”

Taken together, the study’s findings are “a good message to physicians just to be mindful that these differences do exist and not to just draw from clinical trials to inform your patients,” she said. “You can sort of think about what you are telling them to let them know that the information you are giving them is coming from trials that might not be reflective of what we see in the general population.”

The survival gaps likely stem in part from the often-strict eligibility criteria used in clinical trials, according to Ms. Wang, who is a medical student at the University of California, San Diego.

“When you are designing clinical trials, you have a set of criteria that a patient has to meet before they are even allowed to enroll, so already, you might kind of be drawing from an unrepresentative sample when you start these trials,” she elaborated. “And so we think that a lot of that plays into why you see these differences between what the trial concludes and what SEER shows.”

A previous similar study compared survival among patients with a variety of cancers treated in versus out of clinical trials (J. Natl. Cancer Inst. 2014 [doi:10.1093/jnci/dju002]), Ms. Wang noted at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“They found that initially, the clinical trial patients did better, but after 5 years or so, it kind of evened out,” she said. “What we found was up until 5 years and even longer, you do see a difference.”

SAN FRANCISCO – Baseline levels of alpha-fetoprotein (AFP) may help identify patients with advanced hepatocellular carcinoma (HCC) who are most likely to benefit from treatment with the antiangiogenic agent ramucirumab, suggests a study reported at the 2015 Gastrointestinal Cancers Symposium.

Researchers led by Dr. Andrew X. Zhu of Harvard Medical School and director of Liver Cancer Research at the Massachusetts General Hospital, both in Boston, performed subgroup analyses of data from the randomized phase III REACH trial. The trial pitted ramucirumab (Cyramza) against placebo as second-line therapy in 544 patients with advanced HCC who had previously received sorafenib.

Ramucirumab is an antibody to the vascular endothelial growth factor receptor 2 (VEGFR2). It is currently approved by the U.S. Food and Drug Administration for the treatment of esophagogastric cancers and non–small cell lung cancer.

The trial, which was sponsored by Eli Lilly, failed to meet its primary endpoint of significantly improving overall survival (Ann. Oncol. 2014;25 [doi:10.1093/annonc/mdu438.16]), according to Dr. Zhu.

But the new, prespecified subgroup analyses showed that patients having a baseline AFP level of 400 ng/mL or higher – typically a poor prognostic factor – had a one-third reduction in the risk of death if given ramucirumab instead of placebo (median survival, 7.8 vs. 4.2 months; hazard ratio, 0.67; P = .0059), he reported at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

The findings were similar in post hoc analyses among patients who met an alternate definition of elevated AFP level of at least 1.5 times the upper limit of normal (median survival, 8.6 vs. 5.7 months; HR, 0.75; P = .0088).

Additionally, threshold analyses indicated that absolute benefit increased with AFP level in the trial population as a whole; however, patients having levels as low as approximately 10 ng/mL still derived some benefit.

“Further analysis from the REACH study has identified AFP as a potential marker for selecting patients who may benefit from ramucirumab treatment in advanced HCC,” Dr. Zhu commented. “A robust and clinically meaningful improvement in overall survival was observed in the population with an elevated AFP level above 400 ng/mL.”

Session cochair W. Ray Kim, chief of the division of gastroenterology and hepatology, department of medicine, Stanford (Calif.) University, expressed some skepticism about the new data, however, noting the lack of ramucirumab benefit in the trial population overall but the presence of benefit down to normal AFP levels in the post hoc threshold analysis. “The two results don’t seem to be congruent with each other,” Dr. Kim commented.

Various methods can be used to model the baseline AFP threshold to predict the likely benefit, Dr. Zhu replied. “Suffice it to say that if you do different modeling, the results may be slightly different. I think that probably the 400 ng/mL still gives us the confidence as best as we could. But there is no doubt in my mind that between the upper limit of normal and 400 ng/mL, there will be patients who are also likely to benefit. And I think the cutoff for this will continue to be an issue.”

A session attendee asked, “What is the underlying biology, why [do patients with] higher AFP levels respond to antiangiogenesis treatment?”

“This is obviously a very critical question that we are actively pursuing,” Dr. Zhu replied. “We think that there may be some underlying link for those patients with high AFP with increased angiogenesis. And whether this is purely driven by VEGF or VEGFR2, I don’t think that the literature is actually very clear. There is definitely mounting evidence suggesting the high-AFP group is really a unique subgroup of patients with a unique genetic signature. But how this interlink is playing, I think at this point we don’t have the clear answer.”

Ramucirumab was similarly well tolerated in patients with AFP levels of 400 ng/mL or higher, as compared with counterparts having lower levels, reported Dr. Zhu, who disclosed that he has a consulting or advisory role with Celgene, Daiichi Sankyo, Eisai, Exelixis, and Sanofi. Notably, the rate of grade 3 or worse liver injury or failure was 22% with ramucirumab vs. 31% with placebo in the high-AFP group.

“Further investigation of the relationship between baseline AFP levels and angiogenesis inhibition is currently ongoing to better understand the mechanism of ramucirumab action in HCC,” Dr. Zhu said. “Whether there will be a posttreatment response in AFP and whether the posttreatment response will predict the outcome, we are currently analyzing that.”The researchers are additionally evaluating serum biomarkers of angiogenesis. “Unfortunately, we don’t have the archived tissue that may actually allow us to do some more detailed investigation. But I think we will present the circulating angiogenesis-related biomarkers to see whether there will be an additional biomarker that will actually segregate with the elevated AFP,” he concluded.

SAN FRANCISCO – Baseline levels of alpha-fetoprotein (AFP) may help identify patients with advanced hepatocellular carcinoma (HCC) who are most likely to benefit from treatment with the antiangiogenic agent ramucirumab, suggests a study reported at the 2015 Gastrointestinal Cancers Symposium.

Researchers led by Dr. Andrew X. Zhu of Harvard Medical School and director of Liver Cancer Research at the Massachusetts General Hospital, both in Boston, performed subgroup analyses of data from the randomized phase III REACH trial. The trial pitted ramucirumab (Cyramza) against placebo as second-line therapy in 544 patients with advanced HCC who had previously received sorafenib.

Ramucirumab is an antibody to the vascular endothelial growth factor receptor 2 (VEGFR2). It is currently approved by the U.S. Food and Drug Administration for the treatment of esophagogastric cancers and non–small cell lung cancer.

The trial, which was sponsored by Eli Lilly, failed to meet its primary endpoint of significantly improving overall survival (Ann. Oncol. 2014;25 [doi:10.1093/annonc/mdu438.16]), according to Dr. Zhu.

But the new, prespecified subgroup analyses showed that patients having a baseline AFP level of 400 ng/mL or higher – typically a poor prognostic factor – had a one-third reduction in the risk of death if given ramucirumab instead of placebo (median survival, 7.8 vs. 4.2 months; hazard ratio, 0.67; P = .0059), he reported at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

The findings were similar in post hoc analyses among patients who met an alternate definition of elevated AFP level of at least 1.5 times the upper limit of normal (median survival, 8.6 vs. 5.7 months; HR, 0.75; P = .0088).

Additionally, threshold analyses indicated that absolute benefit increased with AFP level in the trial population as a whole; however, patients having levels as low as approximately 10 ng/mL still derived some benefit.

“Further analysis from the REACH study has identified AFP as a potential marker for selecting patients who may benefit from ramucirumab treatment in advanced HCC,” Dr. Zhu commented. “A robust and clinically meaningful improvement in overall survival was observed in the population with an elevated AFP level above 400 ng/mL.”

Session cochair W. Ray Kim, chief of the division of gastroenterology and hepatology, department of medicine, Stanford (Calif.) University, expressed some skepticism about the new data, however, noting the lack of ramucirumab benefit in the trial population overall but the presence of benefit down to normal AFP levels in the post hoc threshold analysis. “The two results don’t seem to be congruent with each other,” Dr. Kim commented.

Various methods can be used to model the baseline AFP threshold to predict the likely benefit, Dr. Zhu replied. “Suffice it to say that if you do different modeling, the results may be slightly different. I think that probably the 400 ng/mL still gives us the confidence as best as we could. But there is no doubt in my mind that between the upper limit of normal and 400 ng/mL, there will be patients who are also likely to benefit. And I think the cutoff for this will continue to be an issue.”

A session attendee asked, “What is the underlying biology, why [do patients with] higher AFP levels respond to antiangiogenesis treatment?”

“This is obviously a very critical question that we are actively pursuing,” Dr. Zhu replied. “We think that there may be some underlying link for those patients with high AFP with increased angiogenesis. And whether this is purely driven by VEGF or VEGFR2, I don’t think that the literature is actually very clear. There is definitely mounting evidence suggesting the high-AFP group is really a unique subgroup of patients with a unique genetic signature. But how this interlink is playing, I think at this point we don’t have the clear answer.”

Ramucirumab was similarly well tolerated in patients with AFP levels of 400 ng/mL or higher, as compared with counterparts having lower levels, reported Dr. Zhu, who disclosed that he has a consulting or advisory role with Celgene, Daiichi Sankyo, Eisai, Exelixis, and Sanofi. Notably, the rate of grade 3 or worse liver injury or failure was 22% with ramucirumab vs. 31% with placebo in the high-AFP group.

“Further investigation of the relationship between baseline AFP levels and angiogenesis inhibition is currently ongoing to better understand the mechanism of ramucirumab action in HCC,” Dr. Zhu said. “Whether there will be a posttreatment response in AFP and whether the posttreatment response will predict the outcome, we are currently analyzing that.”The researchers are additionally evaluating serum biomarkers of angiogenesis. “Unfortunately, we don’t have the archived tissue that may actually allow us to do some more detailed investigation. But I think we will present the circulating angiogenesis-related biomarkers to see whether there will be an additional biomarker that will actually segregate with the elevated AFP,” he concluded.

SAN FRANCISCO – Baseline levels of alpha-fetoprotein (AFP) may help identify patients with advanced hepatocellular carcinoma (HCC) who are most likely to benefit from treatment with the antiangiogenic agent ramucirumab, suggests a study reported at the 2015 Gastrointestinal Cancers Symposium.

Researchers led by Dr. Andrew X. Zhu of Harvard Medical School and director of Liver Cancer Research at the Massachusetts General Hospital, both in Boston, performed subgroup analyses of data from the randomized phase III REACH trial. The trial pitted ramucirumab (Cyramza) against placebo as second-line therapy in 544 patients with advanced HCC who had previously received sorafenib.

Ramucirumab is an antibody to the vascular endothelial growth factor receptor 2 (VEGFR2). It is currently approved by the U.S. Food and Drug Administration for the treatment of esophagogastric cancers and non–small cell lung cancer.

The trial, which was sponsored by Eli Lilly, failed to meet its primary endpoint of significantly improving overall survival (Ann. Oncol. 2014;25 [doi:10.1093/annonc/mdu438.16]), according to Dr. Zhu.

But the new, prespecified subgroup analyses showed that patients having a baseline AFP level of 400 ng/mL or higher – typically a poor prognostic factor – had a one-third reduction in the risk of death if given ramucirumab instead of placebo (median survival, 7.8 vs. 4.2 months; hazard ratio, 0.67; P = .0059), he reported at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

The findings were similar in post hoc analyses among patients who met an alternate definition of elevated AFP level of at least 1.5 times the upper limit of normal (median survival, 8.6 vs. 5.7 months; HR, 0.75; P = .0088).

Additionally, threshold analyses indicated that absolute benefit increased with AFP level in the trial population as a whole; however, patients having levels as low as approximately 10 ng/mL still derived some benefit.

“Further analysis from the REACH study has identified AFP as a potential marker for selecting patients who may benefit from ramucirumab treatment in advanced HCC,” Dr. Zhu commented. “A robust and clinically meaningful improvement in overall survival was observed in the population with an elevated AFP level above 400 ng/mL.”

Session cochair W. Ray Kim, chief of the division of gastroenterology and hepatology, department of medicine, Stanford (Calif.) University, expressed some skepticism about the new data, however, noting the lack of ramucirumab benefit in the trial population overall but the presence of benefit down to normal AFP levels in the post hoc threshold analysis. “The two results don’t seem to be congruent with each other,” Dr. Kim commented.

Various methods can be used to model the baseline AFP threshold to predict the likely benefit, Dr. Zhu replied. “Suffice it to say that if you do different modeling, the results may be slightly different. I think that probably the 400 ng/mL still gives us the confidence as best as we could. But there is no doubt in my mind that between the upper limit of normal and 400 ng/mL, there will be patients who are also likely to benefit. And I think the cutoff for this will continue to be an issue.”

A session attendee asked, “What is the underlying biology, why [do patients with] higher AFP levels respond to antiangiogenesis treatment?”

“This is obviously a very critical question that we are actively pursuing,” Dr. Zhu replied. “We think that there may be some underlying link for those patients with high AFP with increased angiogenesis. And whether this is purely driven by VEGF or VEGFR2, I don’t think that the literature is actually very clear. There is definitely mounting evidence suggesting the high-AFP group is really a unique subgroup of patients with a unique genetic signature. But how this interlink is playing, I think at this point we don’t have the clear answer.”

Ramucirumab was similarly well tolerated in patients with AFP levels of 400 ng/mL or higher, as compared with counterparts having lower levels, reported Dr. Zhu, who disclosed that he has a consulting or advisory role with Celgene, Daiichi Sankyo, Eisai, Exelixis, and Sanofi. Notably, the rate of grade 3 or worse liver injury or failure was 22% with ramucirumab vs. 31% with placebo in the high-AFP group.

“Further investigation of the relationship between baseline AFP levels and angiogenesis inhibition is currently ongoing to better understand the mechanism of ramucirumab action in HCC,” Dr. Zhu said. “Whether there will be a posttreatment response in AFP and whether the posttreatment response will predict the outcome, we are currently analyzing that.”The researchers are additionally evaluating serum biomarkers of angiogenesis. “Unfortunately, we don’t have the archived tissue that may actually allow us to do some more detailed investigation. But I think we will present the circulating angiogenesis-related biomarkers to see whether there will be an additional biomarker that will actually segregate with the elevated AFP,” he concluded.

SAN FRANCISCO – Statin use confers a survival benefit in patients with colorectal cancer, suggests a systematic review and meta-analysis presented at the annual Gastrointestinal Cancers Symposium.

Investigators analyzed data from seven observational studies having a total of 64,773 patients with this cancer, a fifth of whom were using statins. Results showed that statin users had a nearly 30% reduction in the adjusted risk of all-cause mortality relative to nonusers, Dr. Arjun Gupta, the lead investigator, reported in a poster session at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“There is a lot of interest in non–cytotoxic chemotherapy drugs that can be used to treat cancer,” he said in an interview. “Thirty percent is a very, very significant number – we use chemotherapy drugs even if they have just a 10% survival benefit. So I am hopeful that this will help people.”

Accumulating preclinical data suggest that statins have anticancer actions, inhibiting cell proliferation and angiogenesis, and inducing apoptosis, according to Dr. Gupta, who is a resident in internal medicine at the University of Texas Southwestern Medical Center, Dallas. Previous studies have shown use to be associated with a decreased risk of developing colorectal cancer, but its impact on established disease has not been well assessed on a large scale.

“This is all observational data. There is no randomized controlled trial that’s been done,” he acknowledged. “But these data certainly seem to point out that this is something we can do. It’s a cheap and easy, safe drug which people take for years on end without any complications.”

At present, statins are approved by the Food and Drug Administration only for lipid-lowering indications, he noted. However, patients with colorectal cancer often have cardiovascular risk factors that make them candidates for statins.

“No one really gets a statin right now for colon cancer. We are just sort of lucky, maybe, that so many people with colon cancer have high cholesterol and are getting these drugs,” Dr. Gupta said. “But hopefully, my dream is 5 years down the line, it will be prescribed to people for this indication.”

Study results showed that in multivariate analyses, patients using statins were 26% less likely to die of any cause (hazard ratio, 0.74). Findings were similar whether they had colon cancer (hazard ratio, 0.79) or rectal cancer (hazard ratio, 0.63).

When analyses were restricted to studies that adjusted for concomitant use of aspirin and nonsteroidal anti-inflammatory drugs, statin users had significantly reduced risks of both all-cause mortality (hazard ratio, 0.74) and colorectal cancer–specific mortality (HR, 0.76), reported Dr. Gupta.

Patients who started using the medications after their cancer diagnosis had a significantly reduced risk of colorectal cancer-specific mortality (HR, 0.70) but not all-cause mortality.

Dr. Gupta disclosed that he had no relevant conflicts of interest.

SAN FRANCISCO – Statin use confers a survival benefit in patients with colorectal cancer, suggests a systematic review and meta-analysis presented at the annual Gastrointestinal Cancers Symposium.

Investigators analyzed data from seven observational studies having a total of 64,773 patients with this cancer, a fifth of whom were using statins. Results showed that statin users had a nearly 30% reduction in the adjusted risk of all-cause mortality relative to nonusers, Dr. Arjun Gupta, the lead investigator, reported in a poster session at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“There is a lot of interest in non–cytotoxic chemotherapy drugs that can be used to treat cancer,” he said in an interview. “Thirty percent is a very, very significant number – we use chemotherapy drugs even if they have just a 10% survival benefit. So I am hopeful that this will help people.”

Accumulating preclinical data suggest that statins have anticancer actions, inhibiting cell proliferation and angiogenesis, and inducing apoptosis, according to Dr. Gupta, who is a resident in internal medicine at the University of Texas Southwestern Medical Center, Dallas. Previous studies have shown use to be associated with a decreased risk of developing colorectal cancer, but its impact on established disease has not been well assessed on a large scale.

“This is all observational data. There is no randomized controlled trial that’s been done,” he acknowledged. “But these data certainly seem to point out that this is something we can do. It’s a cheap and easy, safe drug which people take for years on end without any complications.”

At present, statins are approved by the Food and Drug Administration only for lipid-lowering indications, he noted. However, patients with colorectal cancer often have cardiovascular risk factors that make them candidates for statins.

“No one really gets a statin right now for colon cancer. We are just sort of lucky, maybe, that so many people with colon cancer have high cholesterol and are getting these drugs,” Dr. Gupta said. “But hopefully, my dream is 5 years down the line, it will be prescribed to people for this indication.”

Study results showed that in multivariate analyses, patients using statins were 26% less likely to die of any cause (hazard ratio, 0.74). Findings were similar whether they had colon cancer (hazard ratio, 0.79) or rectal cancer (hazard ratio, 0.63).

When analyses were restricted to studies that adjusted for concomitant use of aspirin and nonsteroidal anti-inflammatory drugs, statin users had significantly reduced risks of both all-cause mortality (hazard ratio, 0.74) and colorectal cancer–specific mortality (HR, 0.76), reported Dr. Gupta.

Patients who started using the medications after their cancer diagnosis had a significantly reduced risk of colorectal cancer-specific mortality (HR, 0.70) but not all-cause mortality.

Dr. Gupta disclosed that he had no relevant conflicts of interest.

SAN FRANCISCO – Statin use confers a survival benefit in patients with colorectal cancer, suggests a systematic review and meta-analysis presented at the annual Gastrointestinal Cancers Symposium.

Investigators analyzed data from seven observational studies having a total of 64,773 patients with this cancer, a fifth of whom were using statins. Results showed that statin users had a nearly 30% reduction in the adjusted risk of all-cause mortality relative to nonusers, Dr. Arjun Gupta, the lead investigator, reported in a poster session at the meeting cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“There is a lot of interest in non–cytotoxic chemotherapy drugs that can be used to treat cancer,” he said in an interview. “Thirty percent is a very, very significant number – we use chemotherapy drugs even if they have just a 10% survival benefit. So I am hopeful that this will help people.”

Accumulating preclinical data suggest that statins have anticancer actions, inhibiting cell proliferation and angiogenesis, and inducing apoptosis, according to Dr. Gupta, who is a resident in internal medicine at the University of Texas Southwestern Medical Center, Dallas. Previous studies have shown use to be associated with a decreased risk of developing colorectal cancer, but its impact on established disease has not been well assessed on a large scale.

“This is all observational data. There is no randomized controlled trial that’s been done,” he acknowledged. “But these data certainly seem to point out that this is something we can do. It’s a cheap and easy, safe drug which people take for years on end without any complications.”

At present, statins are approved by the Food and Drug Administration only for lipid-lowering indications, he noted. However, patients with colorectal cancer often have cardiovascular risk factors that make them candidates for statins.

“No one really gets a statin right now for colon cancer. We are just sort of lucky, maybe, that so many people with colon cancer have high cholesterol and are getting these drugs,” Dr. Gupta said. “But hopefully, my dream is 5 years down the line, it will be prescribed to people for this indication.”

Study results showed that in multivariate analyses, patients using statins were 26% less likely to die of any cause (hazard ratio, 0.74). Findings were similar whether they had colon cancer (hazard ratio, 0.79) or rectal cancer (hazard ratio, 0.63).

When analyses were restricted to studies that adjusted for concomitant use of aspirin and nonsteroidal anti-inflammatory drugs, statin users had significantly reduced risks of both all-cause mortality (hazard ratio, 0.74) and colorectal cancer–specific mortality (HR, 0.76), reported Dr. Gupta.

Patients who started using the medications after their cancer diagnosis had a significantly reduced risk of colorectal cancer-specific mortality (HR, 0.70) but not all-cause mortality.

Dr. Gupta disclosed that he had no relevant conflicts of interest.

SAN FRANCISCO – None of the phase III randomized controlled trials in metastatic colorectal cancer conducted during 1980-1989 used progression-free survival as their endpoint, whereas approximately 40% of those conducted during 2010-2014 did, according to an analysis reported at the 2015 Gastrointestinal Cancers Symposium, sponsored by the American Society of Clinical Oncology.

Investigators led by Dr. Sunil Parimi, a fellow at the Tom Baker Cancer Centre, University of Calgary, Alberta, studied the characteristics of 192 phase III randomized controlled trials in metastatic colorectal cancer (mCRC) conducted between 1980 and 2014 and reported in an abstract or published article. To assess temporal trends, they split the trials into decades.

Susan London/Frontline Medical News

The use of overall survival as an endpoint peaked at 35% of trials in 2000-2009 and fell thereafter. None of the trials conducted in the first decade used progression-free survival (PFS) as their endpoint, whereas approximately 40% of those conducted in 2010-2014 did.

This trend “is one of the most surprising and interesting changes to me that has occurred over the decades,” Dr. Parimi commented in an interview. “Before, we used to use hard endpoints such as overall survival and quality of life, especially from the metastatic standpoint, and now that’s gradually started to taper off and surrogate endpoints have started to take the lead, progression-free survival in particular.”

Its use has likely contributed to increases in the proportions of trials meeting their primary endpoint (from 11% to 42%) and reporting in their conclusions that their results were positive (from 33% to 53%), “either warranting further study or endorsing a drug to be used in the general population,” he added.

Yet, PFS has not been validated as a surrogate for overall survival in this context, according to Dr. Parimi. “It is definitely still controversial whether or not we are looking at the outcomes that really matter in the mCRC population, or is it just something that’s more attainable,” he elaborated. “The proponents of it would say, it’s more difficult to find overall survival with later-line therapy, with cross-over trial designs, which are all new advents. So that’s why, partially at least, there is more of a dependence on progression-free survival as an endpoint.”

The proportion of trials relying on industry funding rose from 1990 onward, from roughly 10% to 60%. There were also increases during the study period in the median number of agents used in investigational arms (from 1.5 to 2.5) and in the share of trials evaluating targeted therapies (from 0% to 68%), Dr. Parimi reported in a poster session.

The proportion of the trials that were published more than doubled, going from 39% of those conducted during 1980-1989 to 82% of those conducted during 2000-2014.

A variety of factors may be contributing to the observed trends, he speculated. “It’s pressure from various angles that’s driving people to come up with a positive study, quote unquote, regardless of what the outcome is. The intention behind doing this study was just to raise awareness of what the shifts are and then subsequently, we can debate the ramifications or the implications of those shifts.”

Although median progression-free and overall survival on the trials increased during the study period, the absolute magnitude of benefit derived from the investigational therapy relative to the control therapy did not increase significantly, hovering at about a 1-month gain for each endpoint across decades.

“The improvements that we make are always small amounts – there have not been any big explosions,” Dr. Parimi commented. “There are a number of reasons why that may be. But maybe it’s because we have come up with so many therapeutics, and so much research has been put into this already that we just are not making those dramatic findings.”

The study’s results have important implications when it comes to allocation of research funding, according to Dr. Parimi, who disclosed that he had no relevant conflicts of interest.

“I think that if we did fewer studies that had a higher standard of efficacy or outcome, we’d save more money on the drug-development process, and we could shift it to areas where it was truly needed. And I actually think that we can accelerate drug development in that way, as opposed to coming out with multiple bodies of literature that disperse the amount of funds that we use for different projects, and drugs which may or may not have true hard-outcome benefits, at least in the eyes of many,” he concluded. “So if we can allow for that paradigm shift, or maybe rather go back to that, fewer trials with more quality would definitely be advantageous.”

SAN FRANCISCO – None of the phase III randomized controlled trials in metastatic colorectal cancer conducted during 1980-1989 used progression-free survival as their endpoint, whereas approximately 40% of those conducted during 2010-2014 did, according to an analysis reported at the 2015 Gastrointestinal Cancers Symposium, sponsored by the American Society of Clinical Oncology.

Investigators led by Dr. Sunil Parimi, a fellow at the Tom Baker Cancer Centre, University of Calgary, Alberta, studied the characteristics of 192 phase III randomized controlled trials in metastatic colorectal cancer (mCRC) conducted between 1980 and 2014 and reported in an abstract or published article. To assess temporal trends, they split the trials into decades.

Susan London/Frontline Medical News

The use of overall survival as an endpoint peaked at 35% of trials in 2000-2009 and fell thereafter. None of the trials conducted in the first decade used progression-free survival (PFS) as their endpoint, whereas approximately 40% of those conducted in 2010-2014 did.

This trend “is one of the most surprising and interesting changes to me that has occurred over the decades,” Dr. Parimi commented in an interview. “Before, we used to use hard endpoints such as overall survival and quality of life, especially from the metastatic standpoint, and now that’s gradually started to taper off and surrogate endpoints have started to take the lead, progression-free survival in particular.”

Its use has likely contributed to increases in the proportions of trials meeting their primary endpoint (from 11% to 42%) and reporting in their conclusions that their results were positive (from 33% to 53%), “either warranting further study or endorsing a drug to be used in the general population,” he added.

Yet, PFS has not been validated as a surrogate for overall survival in this context, according to Dr. Parimi. “It is definitely still controversial whether or not we are looking at the outcomes that really matter in the mCRC population, or is it just something that’s more attainable,” he elaborated. “The proponents of it would say, it’s more difficult to find overall survival with later-line therapy, with cross-over trial designs, which are all new advents. So that’s why, partially at least, there is more of a dependence on progression-free survival as an endpoint.”

The proportion of trials relying on industry funding rose from 1990 onward, from roughly 10% to 60%. There were also increases during the study period in the median number of agents used in investigational arms (from 1.5 to 2.5) and in the share of trials evaluating targeted therapies (from 0% to 68%), Dr. Parimi reported in a poster session.

The proportion of the trials that were published more than doubled, going from 39% of those conducted during 1980-1989 to 82% of those conducted during 2000-2014.

A variety of factors may be contributing to the observed trends, he speculated. “It’s pressure from various angles that’s driving people to come up with a positive study, quote unquote, regardless of what the outcome is. The intention behind doing this study was just to raise awareness of what the shifts are and then subsequently, we can debate the ramifications or the implications of those shifts.”

Although median progression-free and overall survival on the trials increased during the study period, the absolute magnitude of benefit derived from the investigational therapy relative to the control therapy did not increase significantly, hovering at about a 1-month gain for each endpoint across decades.

“The improvements that we make are always small amounts – there have not been any big explosions,” Dr. Parimi commented. “There are a number of reasons why that may be. But maybe it’s because we have come up with so many therapeutics, and so much research has been put into this already that we just are not making those dramatic findings.”

The study’s results have important implications when it comes to allocation of research funding, according to Dr. Parimi, who disclosed that he had no relevant conflicts of interest.

“I think that if we did fewer studies that had a higher standard of efficacy or outcome, we’d save more money on the drug-development process, and we could shift it to areas where it was truly needed. And I actually think that we can accelerate drug development in that way, as opposed to coming out with multiple bodies of literature that disperse the amount of funds that we use for different projects, and drugs which may or may not have true hard-outcome benefits, at least in the eyes of many,” he concluded. “So if we can allow for that paradigm shift, or maybe rather go back to that, fewer trials with more quality would definitely be advantageous.”

SAN FRANCISCO – None of the phase III randomized controlled trials in metastatic colorectal cancer conducted during 1980-1989 used progression-free survival as their endpoint, whereas approximately 40% of those conducted during 2010-2014 did, according to an analysis reported at the 2015 Gastrointestinal Cancers Symposium, sponsored by the American Society of Clinical Oncology.

Investigators led by Dr. Sunil Parimi, a fellow at the Tom Baker Cancer Centre, University of Calgary, Alberta, studied the characteristics of 192 phase III randomized controlled trials in metastatic colorectal cancer (mCRC) conducted between 1980 and 2014 and reported in an abstract or published article. To assess temporal trends, they split the trials into decades.

Susan London/Frontline Medical News

The use of overall survival as an endpoint peaked at 35% of trials in 2000-2009 and fell thereafter. None of the trials conducted in the first decade used progression-free survival (PFS) as their endpoint, whereas approximately 40% of those conducted in 2010-2014 did.

This trend “is one of the most surprising and interesting changes to me that has occurred over the decades,” Dr. Parimi commented in an interview. “Before, we used to use hard endpoints such as overall survival and quality of life, especially from the metastatic standpoint, and now that’s gradually started to taper off and surrogate endpoints have started to take the lead, progression-free survival in particular.”

Its use has likely contributed to increases in the proportions of trials meeting their primary endpoint (from 11% to 42%) and reporting in their conclusions that their results were positive (from 33% to 53%), “either warranting further study or endorsing a drug to be used in the general population,” he added.

Yet, PFS has not been validated as a surrogate for overall survival in this context, according to Dr. Parimi. “It is definitely still controversial whether or not we are looking at the outcomes that really matter in the mCRC population, or is it just something that’s more attainable,” he elaborated. “The proponents of it would say, it’s more difficult to find overall survival with later-line therapy, with cross-over trial designs, which are all new advents. So that’s why, partially at least, there is more of a dependence on progression-free survival as an endpoint.”

The proportion of trials relying on industry funding rose from 1990 onward, from roughly 10% to 60%. There were also increases during the study period in the median number of agents used in investigational arms (from 1.5 to 2.5) and in the share of trials evaluating targeted therapies (from 0% to 68%), Dr. Parimi reported in a poster session.

The proportion of the trials that were published more than doubled, going from 39% of those conducted during 1980-1989 to 82% of those conducted during 2000-2014.

A variety of factors may be contributing to the observed trends, he speculated. “It’s pressure from various angles that’s driving people to come up with a positive study, quote unquote, regardless of what the outcome is. The intention behind doing this study was just to raise awareness of what the shifts are and then subsequently, we can debate the ramifications or the implications of those shifts.”

Although median progression-free and overall survival on the trials increased during the study period, the absolute magnitude of benefit derived from the investigational therapy relative to the control therapy did not increase significantly, hovering at about a 1-month gain for each endpoint across decades.

“The improvements that we make are always small amounts – there have not been any big explosions,” Dr. Parimi commented. “There are a number of reasons why that may be. But maybe it’s because we have come up with so many therapeutics, and so much research has been put into this already that we just are not making those dramatic findings.”

The study’s results have important implications when it comes to allocation of research funding, according to Dr. Parimi, who disclosed that he had no relevant conflicts of interest.

“I think that if we did fewer studies that had a higher standard of efficacy or outcome, we’d save more money on the drug-development process, and we could shift it to areas where it was truly needed. And I actually think that we can accelerate drug development in that way, as opposed to coming out with multiple bodies of literature that disperse the amount of funds that we use for different projects, and drugs which may or may not have true hard-outcome benefits, at least in the eyes of many,” he concluded. “So if we can allow for that paradigm shift, or maybe rather go back to that, fewer trials with more quality would definitely be advantageous.”

SAN FRANCISCO – Patients with early gastric cancer have less postoperative morbidity if they undergo laparoscopic instead of open distal gastrectomy, according to safety results of a phase III trial presented at the at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The trial – the first in a series by the Korean Laparo-endoscopic Gastrointestinal Surgery Study Group (KLASS-01) – was conducted among 1,416 patients with clinical stage I disease in Korea, where the proportion of esophagogastric cancers caught in early stages has increased with the introduction of a national screening program. The patients were randomized evenly to laparoscopic or open surgery.

Main results showed mortality was similarly low for the open and laparoscopic approaches. But the laparoscopic group had half the rate of wound complications and, in multivariate analysis, a 41% lower risk of postoperative morbidity.

“Laparoscopy-assisted distal gastrectomy for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complications compared with conventional open surgery,” concluded first author Dr. Hyuk-Joon Lee, a gastrointestinal surgeon at the Seoul National University Hospital, Korea.

Invited discussant Dr. Michael Kent of Harvard Medical School, director of minimally invasive thoracic surgery at Beth Israel Deaconess Medical Center, Boston, said, “It is clear that the KLASS study is the largest by far to evaluate laparoscopic gastrectomy.”

A similar trial in the setting of early colorectal cancer (N. Engl. J. Med. 2004;350:2050-9) led to rapid uptake of laparoscopic resection for those patients at high-volume centers, he noted. “Although we still await survival data from the KLASS study, I anticipate that laparoscopic gastrectomy will likewise become the preferred approach in high-volume centers, especially in countries such as Korea with a national screening program.

“However, I do not think that open gastrectomy is an operation of the past,” he added. “For one, the benefits have not been shown yet in advanced gastric cancer. Also, in low-volume centers, the expertise in laparoscopic surgery may not be sufficient to warrant this approach. I should also add that body habitus may render this operation more difficult in obese patients.”

Dr. Kent pointed out that patients with T1a disease have yet another option, endoscopic resection, which has been found to yield good results at least in a single-center retrospective study (Surg. Endosc. 2013;27:4250-8). “In regards to future clinical trials, I believe it would be important to determine which patients require surgical as opposed to an endoscopic resection,” he concluded.

A previously reported interim analysis of the KLASS-01 trial showed no significant difference in morbidity and mortality between the laparoscopic and open groups, allowing the trial to continue (Ann. Surg. 2010;251:417-20).

Eighty percent of patients on the trial had T1 disease. Within this subset, about 60% had T1a and 40% had T1b disease, Dr. Lee said.

In modified intention-to-treat analyses, patients in the laparoscopic group had a longer operation time (185 vs. 146 minutes) and fewer lymph nodes retrieved (41 vs. 43). But they had a lower estimated blood loss (119 vs. 194 mL) and shorter hospital stay (7.2 vs. 8.0 days).

The rate of surgical mortality was less than 1% and the rate of reoperation was about 1%, with no significant differences between groups.

Patients in the laparoscopic group had lower 30-day rates of postoperative morbidity (13.7% vs. 18.9%, P = .009), and the benefit of the less invasive approach remained significant after multivariate adjustment (odds ratio, 0.59; P = .001). Wound complications were half as common with laparoscopy (3.6% vs. 7.0%, P = .005).

Data on 5-year overall survival, the primary endpoint of the KLASS-01 trial, are expected later this year.

Dr. Kent asked, “In your country, for those patients with clinical T1a disease, how is a decision made regarding therapy?”

“I think if we can accurately diagnose the T stage as well as the N stage, we can surely adapt the endoscopic treatment for all the T1a cancer patients,” Dr. Lee replied. Such diagnosis has proved challenging, he added. Endoscopic resection is usually reserved for patients with tumors less than 2 cm in diameter showing differentiated histology and not invading the mucosa. “We have to move to the more accurate diagnosis of the TNM stage,” he concluded.

SAN FRANCISCO – Patients with early gastric cancer have less postoperative morbidity if they undergo laparoscopic instead of open distal gastrectomy, according to safety results of a phase III trial presented at the at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The trial – the first in a series by the Korean Laparo-endoscopic Gastrointestinal Surgery Study Group (KLASS-01) – was conducted among 1,416 patients with clinical stage I disease in Korea, where the proportion of esophagogastric cancers caught in early stages has increased with the introduction of a national screening program. The patients were randomized evenly to laparoscopic or open surgery.

Main results showed mortality was similarly low for the open and laparoscopic approaches. But the laparoscopic group had half the rate of wound complications and, in multivariate analysis, a 41% lower risk of postoperative morbidity.

“Laparoscopy-assisted distal gastrectomy for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complications compared with conventional open surgery,” concluded first author Dr. Hyuk-Joon Lee, a gastrointestinal surgeon at the Seoul National University Hospital, Korea.

Invited discussant Dr. Michael Kent of Harvard Medical School, director of minimally invasive thoracic surgery at Beth Israel Deaconess Medical Center, Boston, said, “It is clear that the KLASS study is the largest by far to evaluate laparoscopic gastrectomy.”

A similar trial in the setting of early colorectal cancer (N. Engl. J. Med. 2004;350:2050-9) led to rapid uptake of laparoscopic resection for those patients at high-volume centers, he noted. “Although we still await survival data from the KLASS study, I anticipate that laparoscopic gastrectomy will likewise become the preferred approach in high-volume centers, especially in countries such as Korea with a national screening program.

“However, I do not think that open gastrectomy is an operation of the past,” he added. “For one, the benefits have not been shown yet in advanced gastric cancer. Also, in low-volume centers, the expertise in laparoscopic surgery may not be sufficient to warrant this approach. I should also add that body habitus may render this operation more difficult in obese patients.”

Dr. Kent pointed out that patients with T1a disease have yet another option, endoscopic resection, which has been found to yield good results at least in a single-center retrospective study (Surg. Endosc. 2013;27:4250-8). “In regards to future clinical trials, I believe it would be important to determine which patients require surgical as opposed to an endoscopic resection,” he concluded.

A previously reported interim analysis of the KLASS-01 trial showed no significant difference in morbidity and mortality between the laparoscopic and open groups, allowing the trial to continue (Ann. Surg. 2010;251:417-20).

Eighty percent of patients on the trial had T1 disease. Within this subset, about 60% had T1a and 40% had T1b disease, Dr. Lee said.

In modified intention-to-treat analyses, patients in the laparoscopic group had a longer operation time (185 vs. 146 minutes) and fewer lymph nodes retrieved (41 vs. 43). But they had a lower estimated blood loss (119 vs. 194 mL) and shorter hospital stay (7.2 vs. 8.0 days).

The rate of surgical mortality was less than 1% and the rate of reoperation was about 1%, with no significant differences between groups.

Patients in the laparoscopic group had lower 30-day rates of postoperative morbidity (13.7% vs. 18.9%, P = .009), and the benefit of the less invasive approach remained significant after multivariate adjustment (odds ratio, 0.59; P = .001). Wound complications were half as common with laparoscopy (3.6% vs. 7.0%, P = .005).

Data on 5-year overall survival, the primary endpoint of the KLASS-01 trial, are expected later this year.

Dr. Kent asked, “In your country, for those patients with clinical T1a disease, how is a decision made regarding therapy?”

“I think if we can accurately diagnose the T stage as well as the N stage, we can surely adapt the endoscopic treatment for all the T1a cancer patients,” Dr. Lee replied. Such diagnosis has proved challenging, he added. Endoscopic resection is usually reserved for patients with tumors less than 2 cm in diameter showing differentiated histology and not invading the mucosa. “We have to move to the more accurate diagnosis of the TNM stage,” he concluded.

SAN FRANCISCO – Patients with early gastric cancer have less postoperative morbidity if they undergo laparoscopic instead of open distal gastrectomy, according to safety results of a phase III trial presented at the at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

The trial – the first in a series by the Korean Laparo-endoscopic Gastrointestinal Surgery Study Group (KLASS-01) – was conducted among 1,416 patients with clinical stage I disease in Korea, where the proportion of esophagogastric cancers caught in early stages has increased with the introduction of a national screening program. The patients were randomized evenly to laparoscopic or open surgery.

Main results showed mortality was similarly low for the open and laparoscopic approaches. But the laparoscopic group had half the rate of wound complications and, in multivariate analysis, a 41% lower risk of postoperative morbidity.

“Laparoscopy-assisted distal gastrectomy for patients with clinical stage I gastric cancer is safe and has a benefit of lower occurrence of wound complications compared with conventional open surgery,” concluded first author Dr. Hyuk-Joon Lee, a gastrointestinal surgeon at the Seoul National University Hospital, Korea.

Invited discussant Dr. Michael Kent of Harvard Medical School, director of minimally invasive thoracic surgery at Beth Israel Deaconess Medical Center, Boston, said, “It is clear that the KLASS study is the largest by far to evaluate laparoscopic gastrectomy.”

A similar trial in the setting of early colorectal cancer (N. Engl. J. Med. 2004;350:2050-9) led to rapid uptake of laparoscopic resection for those patients at high-volume centers, he noted. “Although we still await survival data from the KLASS study, I anticipate that laparoscopic gastrectomy will likewise become the preferred approach in high-volume centers, especially in countries such as Korea with a national screening program.

“However, I do not think that open gastrectomy is an operation of the past,” he added. “For one, the benefits have not been shown yet in advanced gastric cancer. Also, in low-volume centers, the expertise in laparoscopic surgery may not be sufficient to warrant this approach. I should also add that body habitus may render this operation more difficult in obese patients.”

Dr. Kent pointed out that patients with T1a disease have yet another option, endoscopic resection, which has been found to yield good results at least in a single-center retrospective study (Surg. Endosc. 2013;27:4250-8). “In regards to future clinical trials, I believe it would be important to determine which patients require surgical as opposed to an endoscopic resection,” he concluded.

A previously reported interim analysis of the KLASS-01 trial showed no significant difference in morbidity and mortality between the laparoscopic and open groups, allowing the trial to continue (Ann. Surg. 2010;251:417-20).

Eighty percent of patients on the trial had T1 disease. Within this subset, about 60% had T1a and 40% had T1b disease, Dr. Lee said.

In modified intention-to-treat analyses, patients in the laparoscopic group had a longer operation time (185 vs. 146 minutes) and fewer lymph nodes retrieved (41 vs. 43). But they had a lower estimated blood loss (119 vs. 194 mL) and shorter hospital stay (7.2 vs. 8.0 days).

The rate of surgical mortality was less than 1% and the rate of reoperation was about 1%, with no significant differences between groups.

Patients in the laparoscopic group had lower 30-day rates of postoperative morbidity (13.7% vs. 18.9%, P = .009), and the benefit of the less invasive approach remained significant after multivariate adjustment (odds ratio, 0.59; P = .001). Wound complications were half as common with laparoscopy (3.6% vs. 7.0%, P = .005).

Data on 5-year overall survival, the primary endpoint of the KLASS-01 trial, are expected later this year.

Dr. Kent asked, “In your country, for those patients with clinical T1a disease, how is a decision made regarding therapy?”

“I think if we can accurately diagnose the T stage as well as the N stage, we can surely adapt the endoscopic treatment for all the T1a cancer patients,” Dr. Lee replied. Such diagnosis has proved challenging, he added. Endoscopic resection is usually reserved for patients with tumors less than 2 cm in diameter showing differentiated histology and not invading the mucosa. “We have to move to the more accurate diagnosis of the TNM stage,” he concluded.

SAN FRANCISCO – A nanoliposomal formulation of irinotecan, MM-398, prolongs survival for patients with metastatic pancreatic cancer by nearly 2 months when combined with conventional chemotherapy drugs, according to an expanded analysis of the NAPOLI-1 trial. Results were reported at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“This study’s intention-to-treat analysis demonstrated a statistically significant increase in overall survival with the MM-398 plus 5-FU/LV combination … over 5-FU/LV,” said Dr. Li-Tzong Chen of the National Institute of Cancer Research, Tainan, Taiwan. “The safety profile suggests the combination is associated with a manageable toxicity profile.”

In contrast, analyses did not show any significant survival advantage of monotherapy with MM-398 (also known as nal-IRI), which achieves extended circulation of irinotecan in the blood relative to the conventional formulation.

As a result of accumulated data, MM-398 in combination with 5-FU/LV has received fast-track status from the Food and Drug Administration.

“The survival was similar to previous reports of FOLFIRI in second-line pancreas cancer,” said invited discussant Dr. Laura W. Goff, assistant professor of medicine (hematology/oncology) at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. “MM-398 appears to have activity in combination with 5-FU/LV in previously treated pancreas cancer.”

Session attendee Dr. Hanna Sanoff of the UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said, “I’d like to ask a little bit of a provocative question if I could. [Dr. Goff] showed us data that FOLFIRI actually looked pretty similar to nal-irinotecan and fluorouracil, so do you think that this warrants FDA approval in the absence of an appropriate comparator with the existing cheaper drug?”

“At the current time, no, I would not approve FDA approval,” Dr. Goff replied. “But I think it would be interesting to see where that would shake out. Obviously, we see this in pancreas cancer as well as in other regimens, there is not as much interest in investigating the standard already-approved therapies. I don’t know if MM-398 with 5FU is significantly different than FOLFIRI. But I don’t have a lot of clinical experience with it.”

In additional comments provided in an interview, Dr. Goff said, “I am always happy to have more options in pancreas cancer … Figuring out what to do with [MM-398] is going to be the hard part, but I think it will be exciting to see how it translates into other regimens, possibly even in combination with oxaliplatin; I think the company has that planned. And certainly seeing where this has a role, either in front line or in previously treated gemcitabine patients, is going to be important.”

“It will require bigger studies to sort out exactly how efficacious it is and where the best place to use it is going to be, but it’s exciting to have agents to explore,” she concluded.

The international randomized phase III trial, sponsored by Merrimack Pharmaceuticals, enrolled 417 patients with metastatic pancreatic cancer who had previously received gemcitabine-based therapy. They were randomized to receive the investigational agent MM-398 alone, 5-fluorouracil (5-FU) plus leucovorin (LV) alone, or the combination.

Intention-to-treat analysis showed that median overall survival was 4.2 months with 5-FU/LV alone but 6.1 months with MM-398 plus 5-FU/LV (hazard ratio, 0.57; P = .0009), Dr. Chen reported.

Findings were similar across subgroups and in the per-protocol population, defined as patients who received at least 80% of the dose intensity of the protocol-defined treatment during the first 6 weeks of treatment (8.9 vs. 5.1 months; hazard ratio, 0.47; P = .0018).

In addition, the MM-398 plus 5-FU/LV combination was associated with a better median progression-free survival (3.1 vs. 1.5 months, P = .0001), overall response rate (16% vs. 1%, P less than .001), and cancer antigen 19-9 (CA19-9) response rate (36% vs. 12%, P = .0009).

The combination did lead to higher rates of dose reductions and dose delays, but treatment discontinuations were generally similar at 11% with the combination and 8% with 5-FU/LV alone.

Patients in the combination group were more likely to experience various grade 3 or worse toxicities, such as fatigue (14% vs. 4%), diarrhea (13% vs. 5%), and a reduction in neutrophil count (20% vs. 2%).

SAN FRANCISCO – A nanoliposomal formulation of irinotecan, MM-398, prolongs survival for patients with metastatic pancreatic cancer by nearly 2 months when combined with conventional chemotherapy drugs, according to an expanded analysis of the NAPOLI-1 trial. Results were reported at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“This study’s intention-to-treat analysis demonstrated a statistically significant increase in overall survival with the MM-398 plus 5-FU/LV combination … over 5-FU/LV,” said Dr. Li-Tzong Chen of the National Institute of Cancer Research, Tainan, Taiwan. “The safety profile suggests the combination is associated with a manageable toxicity profile.”

In contrast, analyses did not show any significant survival advantage of monotherapy with MM-398 (also known as nal-IRI), which achieves extended circulation of irinotecan in the blood relative to the conventional formulation.

As a result of accumulated data, MM-398 in combination with 5-FU/LV has received fast-track status from the Food and Drug Administration.

“The survival was similar to previous reports of FOLFIRI in second-line pancreas cancer,” said invited discussant Dr. Laura W. Goff, assistant professor of medicine (hematology/oncology) at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. “MM-398 appears to have activity in combination with 5-FU/LV in previously treated pancreas cancer.”

Session attendee Dr. Hanna Sanoff of the UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said, “I’d like to ask a little bit of a provocative question if I could. [Dr. Goff] showed us data that FOLFIRI actually looked pretty similar to nal-irinotecan and fluorouracil, so do you think that this warrants FDA approval in the absence of an appropriate comparator with the existing cheaper drug?”

“At the current time, no, I would not approve FDA approval,” Dr. Goff replied. “But I think it would be interesting to see where that would shake out. Obviously, we see this in pancreas cancer as well as in other regimens, there is not as much interest in investigating the standard already-approved therapies. I don’t know if MM-398 with 5FU is significantly different than FOLFIRI. But I don’t have a lot of clinical experience with it.”

In additional comments provided in an interview, Dr. Goff said, “I am always happy to have more options in pancreas cancer … Figuring out what to do with [MM-398] is going to be the hard part, but I think it will be exciting to see how it translates into other regimens, possibly even in combination with oxaliplatin; I think the company has that planned. And certainly seeing where this has a role, either in front line or in previously treated gemcitabine patients, is going to be important.”

“It will require bigger studies to sort out exactly how efficacious it is and where the best place to use it is going to be, but it’s exciting to have agents to explore,” she concluded.

The international randomized phase III trial, sponsored by Merrimack Pharmaceuticals, enrolled 417 patients with metastatic pancreatic cancer who had previously received gemcitabine-based therapy. They were randomized to receive the investigational agent MM-398 alone, 5-fluorouracil (5-FU) plus leucovorin (LV) alone, or the combination.

Intention-to-treat analysis showed that median overall survival was 4.2 months with 5-FU/LV alone but 6.1 months with MM-398 plus 5-FU/LV (hazard ratio, 0.57; P = .0009), Dr. Chen reported.

Findings were similar across subgroups and in the per-protocol population, defined as patients who received at least 80% of the dose intensity of the protocol-defined treatment during the first 6 weeks of treatment (8.9 vs. 5.1 months; hazard ratio, 0.47; P = .0018).

In addition, the MM-398 plus 5-FU/LV combination was associated with a better median progression-free survival (3.1 vs. 1.5 months, P = .0001), overall response rate (16% vs. 1%, P less than .001), and cancer antigen 19-9 (CA19-9) response rate (36% vs. 12%, P = .0009).

The combination did lead to higher rates of dose reductions and dose delays, but treatment discontinuations were generally similar at 11% with the combination and 8% with 5-FU/LV alone.

Patients in the combination group were more likely to experience various grade 3 or worse toxicities, such as fatigue (14% vs. 4%), diarrhea (13% vs. 5%), and a reduction in neutrophil count (20% vs. 2%).

SAN FRANCISCO – A nanoliposomal formulation of irinotecan, MM-398, prolongs survival for patients with metastatic pancreatic cancer by nearly 2 months when combined with conventional chemotherapy drugs, according to an expanded analysis of the NAPOLI-1 trial. Results were reported at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology.

“This study’s intention-to-treat analysis demonstrated a statistically significant increase in overall survival with the MM-398 plus 5-FU/LV combination … over 5-FU/LV,” said Dr. Li-Tzong Chen of the National Institute of Cancer Research, Tainan, Taiwan. “The safety profile suggests the combination is associated with a manageable toxicity profile.”

In contrast, analyses did not show any significant survival advantage of monotherapy with MM-398 (also known as nal-IRI), which achieves extended circulation of irinotecan in the blood relative to the conventional formulation.

As a result of accumulated data, MM-398 in combination with 5-FU/LV has received fast-track status from the Food and Drug Administration.

“The survival was similar to previous reports of FOLFIRI in second-line pancreas cancer,” said invited discussant Dr. Laura W. Goff, assistant professor of medicine (hematology/oncology) at the Vanderbilt-Ingram Cancer Center in Nashville, Tenn. “MM-398 appears to have activity in combination with 5-FU/LV in previously treated pancreas cancer.”

Session attendee Dr. Hanna Sanoff of the UNC Lineberger Comprehensive Cancer Center, Chapel Hill, N.C., said, “I’d like to ask a little bit of a provocative question if I could. [Dr. Goff] showed us data that FOLFIRI actually looked pretty similar to nal-irinotecan and fluorouracil, so do you think that this warrants FDA approval in the absence of an appropriate comparator with the existing cheaper drug?”

“At the current time, no, I would not approve FDA approval,” Dr. Goff replied. “But I think it would be interesting to see where that would shake out. Obviously, we see this in pancreas cancer as well as in other regimens, there is not as much interest in investigating the standard already-approved therapies. I don’t know if MM-398 with 5FU is significantly different than FOLFIRI. But I don’t have a lot of clinical experience with it.”

In additional comments provided in an interview, Dr. Goff said, “I am always happy to have more options in pancreas cancer … Figuring out what to do with [MM-398] is going to be the hard part, but I think it will be exciting to see how it translates into other regimens, possibly even in combination with oxaliplatin; I think the company has that planned. And certainly seeing where this has a role, either in front line or in previously treated gemcitabine patients, is going to be important.”

“It will require bigger studies to sort out exactly how efficacious it is and where the best place to use it is going to be, but it’s exciting to have agents to explore,” she concluded.

The international randomized phase III trial, sponsored by Merrimack Pharmaceuticals, enrolled 417 patients with metastatic pancreatic cancer who had previously received gemcitabine-based therapy. They were randomized to receive the investigational agent MM-398 alone, 5-fluorouracil (5-FU) plus leucovorin (LV) alone, or the combination.

Intention-to-treat analysis showed that median overall survival was 4.2 months with 5-FU/LV alone but 6.1 months with MM-398 plus 5-FU/LV (hazard ratio, 0.57; P = .0009), Dr. Chen reported.

Findings were similar across subgroups and in the per-protocol population, defined as patients who received at least 80% of the dose intensity of the protocol-defined treatment during the first 6 weeks of treatment (8.9 vs. 5.1 months; hazard ratio, 0.47; P = .0018).

In addition, the MM-398 plus 5-FU/LV combination was associated with a better median progression-free survival (3.1 vs. 1.5 months, P = .0001), overall response rate (16% vs. 1%, P less than .001), and cancer antigen 19-9 (CA19-9) response rate (36% vs. 12%, P = .0009).

The combination did lead to higher rates of dose reductions and dose delays, but treatment discontinuations were generally similar at 11% with the combination and 8% with 5-FU/LV alone.

Patients in the combination group were more likely to experience various grade 3 or worse toxicities, such as fatigue (14% vs. 4%), diarrhea (13% vs. 5%), and a reduction in neutrophil count (20% vs. 2%).

SAN FRANCISCO – Famitinib, a novel oral anti-angiogenic agent, prolongs progression-free survival by 1.3 months in patients with metastatic colorectal cancer when given alone as third- or later-line therapy, in a randomized phase II trial.

“This trial reached its primary endpoint,” co–principal investigator Dr. Rui-hua Xu of Sun Yat-Sen University Cancer Center, Guangzhou, China, said at the annual Gastrointestinal Cancers Symposium, sponsored by the American Society of Clinical Oncology.

“Famitinib demonstrated a similar safety profile with other small-molecule anti-VEGFR [vascular endothelial growth factor receptor] agents,” he said.

There was no significant improvement in overall survival, however, although analyses suggested a possible trend toward benefit in the subset of patients with more heavily pretreated disease.

Invited discussant Dr. Wafik S. El-Deiry, professor and the Deputy Cancer Center Director for Translational Research at Fox Chase Cancer Center, Philadelphia, noted that the patients’ previous targeted therapies were not well described. “It is clear that a significant number of patients did get cetuximab [Erbitux] and bevacizumab [Avastin], but the breakdown was not mentioned,” he elaborated.

He compared the trial with the similar CORRECT trial, which led to approval by the Food and Drug Administration of regorafenib (Stivarga) for metastatic colorectal cancer. In that trial, regorafenib monotherapy yielded a progression-free survival benefit of 1.9 months, as well as an overall survival benefit.

“Subgroup analyses supported an impact of regorafenib on overall survival including KRAS-mutant colorectal cancer,” Dr. El-Deiry noted. “The lack of demonstrated efficacy on overall survival by famitinib may be aided if biomarkers are developed or if it is combined with other agents ... I can’t overemphasize the need to develop and incorporate biomarkers so we can learn.

“Famitinib is not better in third line than approved regimens,” he concluded. “However, randomized comparisons or combination regimens may or may not in the future show improved or better outcomes. There is potential for pushing the doses.”

Patients were eligible for the trial if they had experienced failure of at least two prior lines of standard chemotherapy. They were ineligible if they had previously received a tyrosine kinase inhibitor targeting VEGF, had proteinuria or uncontrolled hypertension, or had a tendency for gastrointestinal bleeding.

A total of 154 patients were randomized in 2:1 ratio to double-blind treatment with either single-agent famitinib – a multitargeted tyrosine kinase inhibitor that mainly targets the vascular endothelial growth factor receptor 2 (VEGFR2), c-Kit, and the platelet-derived growth factor receptor (PDGFR) – or placebo, each taken once daily.

Results showed that median progression-free survival was 2.8 months with famitinib versus 1.5 months with placebo (hazard ratio, 0.59; P = .0053), Dr. Xu reported. Findings were similar across subgroups. There was no significant difference in overall survival, which stood at about 7.5 months in each group. The overall response rate was statistically indistinguishable between groups, but the famitinib group had a higher disease control rate (59% vs. 31%, P = .0016).

There was no significant difference in quality of life, according to Dr. Xu, who disclosed that he had no relevant conflicts of interest.

Patients treated with famitinib had a higher rate of grade 3 or worse drug-related adverse events (46% vs. 20%) and drug-related adverse events leading to treatment discontinuation (13% vs. 5%).

The main grade 3 or 4 adverse events in the famitinib group were hypertension (11%), thrombocytopenia (10%), hand-foot syndrome (10%), and neutropenia (9%).

SAN FRANCISCO – Famitinib, a novel oral anti-angiogenic agent, prolongs progression-free survival by 1.3 months in patients with metastatic colorectal cancer when given alone as third- or later-line therapy, in a randomized phase II trial.

“This trial reached its primary endpoint,” co–principal investigator Dr. Rui-hua Xu of Sun Yat-Sen University Cancer Center, Guangzhou, China, said at the annual Gastrointestinal Cancers Symposium, sponsored by the American Society of Clinical Oncology.

“Famitinib demonstrated a similar safety profile with other small-molecule anti-VEGFR [vascular endothelial growth factor receptor] agents,” he said.

There was no significant improvement in overall survival, however, although analyses suggested a possible trend toward benefit in the subset of patients with more heavily pretreated disease.

Invited discussant Dr. Wafik S. El-Deiry, professor and the Deputy Cancer Center Director for Translational Research at Fox Chase Cancer Center, Philadelphia, noted that the patients’ previous targeted therapies were not well described. “It is clear that a significant number of patients did get cetuximab [Erbitux] and bevacizumab [Avastin], but the breakdown was not mentioned,” he elaborated.

He compared the trial with the similar CORRECT trial, which led to approval by the Food and Drug Administration of regorafenib (Stivarga) for metastatic colorectal cancer. In that trial, regorafenib monotherapy yielded a progression-free survival benefit of 1.9 months, as well as an overall survival benefit.

“Subgroup analyses supported an impact of regorafenib on overall survival including KRAS-mutant colorectal cancer,” Dr. El-Deiry noted. “The lack of demonstrated efficacy on overall survival by famitinib may be aided if biomarkers are developed or if it is combined with other agents ... I can’t overemphasize the need to develop and incorporate biomarkers so we can learn.

“Famitinib is not better in third line than approved regimens,” he concluded. “However, randomized comparisons or combination regimens may or may not in the future show improved or better outcomes. There is potential for pushing the doses.”

Patients were eligible for the trial if they had experienced failure of at least two prior lines of standard chemotherapy. They were ineligible if they had previously received a tyrosine kinase inhibitor targeting VEGF, had proteinuria or uncontrolled hypertension, or had a tendency for gastrointestinal bleeding.

A total of 154 patients were randomized in 2:1 ratio to double-blind treatment with either single-agent famitinib – a multitargeted tyrosine kinase inhibitor that mainly targets the vascular endothelial growth factor receptor 2 (VEGFR2), c-Kit, and the platelet-derived growth factor receptor (PDGFR) – or placebo, each taken once daily.

Results showed that median progression-free survival was 2.8 months with famitinib versus 1.5 months with placebo (hazard ratio, 0.59; P = .0053), Dr. Xu reported. Findings were similar across subgroups. There was no significant difference in overall survival, which stood at about 7.5 months in each group. The overall response rate was statistically indistinguishable between groups, but the famitinib group had a higher disease control rate (59% vs. 31%, P = .0016).

There was no significant difference in quality of life, according to Dr. Xu, who disclosed that he had no relevant conflicts of interest.

Patients treated with famitinib had a higher rate of grade 3 or worse drug-related adverse events (46% vs. 20%) and drug-related adverse events leading to treatment discontinuation (13% vs. 5%).

The main grade 3 or 4 adverse events in the famitinib group were hypertension (11%), thrombocytopenia (10%), hand-foot syndrome (10%), and neutropenia (9%).

SAN FRANCISCO – Famitinib, a novel oral anti-angiogenic agent, prolongs progression-free survival by 1.3 months in patients with metastatic colorectal cancer when given alone as third- or later-line therapy, in a randomized phase II trial.

“This trial reached its primary endpoint,” co–principal investigator Dr. Rui-hua Xu of Sun Yat-Sen University Cancer Center, Guangzhou, China, said at the annual Gastrointestinal Cancers Symposium, sponsored by the American Society of Clinical Oncology.

“Famitinib demonstrated a similar safety profile with other small-molecule anti-VEGFR [vascular endothelial growth factor receptor] agents,” he said.

There was no significant improvement in overall survival, however, although analyses suggested a possible trend toward benefit in the subset of patients with more heavily pretreated disease.

Invited discussant Dr. Wafik S. El-Deiry, professor and the Deputy Cancer Center Director for Translational Research at Fox Chase Cancer Center, Philadelphia, noted that the patients’ previous targeted therapies were not well described. “It is clear that a significant number of patients did get cetuximab [Erbitux] and bevacizumab [Avastin], but the breakdown was not mentioned,” he elaborated.

He compared the trial with the similar CORRECT trial, which led to approval by the Food and Drug Administration of regorafenib (Stivarga) for metastatic colorectal cancer. In that trial, regorafenib monotherapy yielded a progression-free survival benefit of 1.9 months, as well as an overall survival benefit.

“Subgroup analyses supported an impact of regorafenib on overall survival including KRAS-mutant colorectal cancer,” Dr. El-Deiry noted. “The lack of demonstrated efficacy on overall survival by famitinib may be aided if biomarkers are developed or if it is combined with other agents ... I can’t overemphasize the need to develop and incorporate biomarkers so we can learn.

“Famitinib is not better in third line than approved regimens,” he concluded. “However, randomized comparisons or combination regimens may or may not in the future show improved or better outcomes. There is potential for pushing the doses.”

Patients were eligible for the trial if they had experienced failure of at least two prior lines of standard chemotherapy. They were ineligible if they had previously received a tyrosine kinase inhibitor targeting VEGF, had proteinuria or uncontrolled hypertension, or had a tendency for gastrointestinal bleeding.

A total of 154 patients were randomized in 2:1 ratio to double-blind treatment with either single-agent famitinib – a multitargeted tyrosine kinase inhibitor that mainly targets the vascular endothelial growth factor receptor 2 (VEGFR2), c-Kit, and the platelet-derived growth factor receptor (PDGFR) – or placebo, each taken once daily.

Results showed that median progression-free survival was 2.8 months with famitinib versus 1.5 months with placebo (hazard ratio, 0.59; P = .0053), Dr. Xu reported. Findings were similar across subgroups. There was no significant difference in overall survival, which stood at about 7.5 months in each group. The overall response rate was statistically indistinguishable between groups, but the famitinib group had a higher disease control rate (59% vs. 31%, P = .0016).

There was no significant difference in quality of life, according to Dr. Xu, who disclosed that he had no relevant conflicts of interest.

Patients treated with famitinib had a higher rate of grade 3 or worse drug-related adverse events (46% vs. 20%) and drug-related adverse events leading to treatment discontinuation (13% vs. 5%).

The main grade 3 or 4 adverse events in the famitinib group were hypertension (11%), thrombocytopenia (10%), hand-foot syndrome (10%), and neutropenia (9%).

SAN FRANCISCO – Giving preoperative chemotherapy directly into the tumor-feeding artery and prophylactically into the common hepatic artery to target any liver micrometastases improves outcomes in patients with early colorectal cancer undergoing curative resection. But benefit is seen mainly in patients with stage III disease.

These were among the key findings of the randomized multicenter phase III PHRAC trial (Preoperative Hepatic and Regional Arterial Chemotherapy) conducted among 688 patients in China with stage II or III colorectal cancer.

Compared with curative resection alone, followed by adjuvant systemic chemotherapy with the modified FOLFOX6 regimen, the addition of preoperative arterial chemotherapy reduced the 5-year estimated risks of disease-free survival events by 40%, of liver metastases by 61%, and of death by 41% in the trial population overall, according to data reported at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. But stratified analyses showed that these benefits were significant only among the patients with stage III disease.

“Preoperative hepatic and regional arterial chemotherapy had no effect on colorectal cancer surgery or postoperative morbidity,” commented lead investigator Jianmin Xu, an oncologist at the Zhongshan Hospital, Fudan University, in Shanghai. This therapy “is safe and feasible and can reduce liver metastasis and improve disease-free survival and overall survival, especially for the stage III patients.”

“Dr. Xu’s study was a positive study, but we have no description of the catheter problems or the number of patients who could be treated,” commented invited discussant Dr. Nancy E. Kemeny of Memorial Sloan-Kettering Cancer Center, New York. Additionally, outcomes in the control group fell short of those seen in patients treated with FOLFOX historically.

Despite accumulating evidence of benefit, the procedure is not yet ready for incorporation into routine care, according to Dr. Kemeny. “Since we don’t have a lot of information about the problems with the catheters or other problems like that, we need a larger, international study. I think one should be done because if you can prevent recurrences right away, which is what this study is suggesting, then that’s very good for these patients. We have ways of dealing with this afterwards, but it would be nice to prevent it right way. So given the fact that we already have five studies suggesting some benefit with this type of treatment, we should move into a large randomized study,” she recommended.

A session attendee noted that although colon cancer most commonly recurs in the liver, rectal cancer most commonly recurs in the pelvis. “Therefore, chemoradiotherapy is the standard of care now [for rectal cancer]. So infusional arterial chemotherapy should be used in patients with colon cancer, I think,” he said.

The patients with rectal cancer received radiation therapy after surgery if needed, Dr. Xu replied. “In the future, we will do subgroup analyses for colon cancer and for rectal cancer,” he added.

In the trial, patients from five hospitals in China were randomized to immediate curative primary surgery or to hepatic and regional arterial chemotherapy – floxuridine (FUDR), mitomycin C, and oxaliplatin delivered to both the main tumor-supplying artery and to the common hepatic artery – followed by curative primary surgery a week later. All patients received the same adjuvant therapy.

In the intention-to-treat population, estimated 5-year disease-free survival, the trial’s primary endpoint, was 75% with preoperative arterial chemotherapy versus 61% without it (hazard ratio, 0.60; P less than .001), reported Dr. Xu, who disclosed no relevant conflicts of interest. Subgroup analyses indicated that the benefit was significant in patients with stage III disease (68% vs. 51%; HR, 0.62; P = .017) but showed only a trend in patients with stage II disease (84% vs. 74%; HR, 0.64; P = .068).

Patients in the arterial chemotherapy group also were less likely to develop liver metastases (8% vs. 18%; HR, 0.39; P less than .001) and had better overall survival (81% vs. 72%, HR, 0.59; P = .003). But subgroup analyses again showed that benefit was significant only in the stage III patients.

Efficacy findings were similar in the trial’s eligible population, which excluded patients who were found to have pathologic stage I or IV disease at surgery and patients who developed metastases within 6 months of surgery.A total of 25% of patients in the arterial chemotherapy group experienced grade 3 toxicity from the procedure. However, the rate of postoperative complications did not differ significantly between the arterial chemotherapy and control groups.

SAN FRANCISCO – Giving preoperative chemotherapy directly into the tumor-feeding artery and prophylactically into the common hepatic artery to target any liver micrometastases improves outcomes in patients with early colorectal cancer undergoing curative resection. But benefit is seen mainly in patients with stage III disease.

These were among the key findings of the randomized multicenter phase III PHRAC trial (Preoperative Hepatic and Regional Arterial Chemotherapy) conducted among 688 patients in China with stage II or III colorectal cancer.

Compared with curative resection alone, followed by adjuvant systemic chemotherapy with the modified FOLFOX6 regimen, the addition of preoperative arterial chemotherapy reduced the 5-year estimated risks of disease-free survival events by 40%, of liver metastases by 61%, and of death by 41% in the trial population overall, according to data reported at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. But stratified analyses showed that these benefits were significant only among the patients with stage III disease.

“Preoperative hepatic and regional arterial chemotherapy had no effect on colorectal cancer surgery or postoperative morbidity,” commented lead investigator Jianmin Xu, an oncologist at the Zhongshan Hospital, Fudan University, in Shanghai. This therapy “is safe and feasible and can reduce liver metastasis and improve disease-free survival and overall survival, especially for the stage III patients.”

“Dr. Xu’s study was a positive study, but we have no description of the catheter problems or the number of patients who could be treated,” commented invited discussant Dr. Nancy E. Kemeny of Memorial Sloan-Kettering Cancer Center, New York. Additionally, outcomes in the control group fell short of those seen in patients treated with FOLFOX historically.

Despite accumulating evidence of benefit, the procedure is not yet ready for incorporation into routine care, according to Dr. Kemeny. “Since we don’t have a lot of information about the problems with the catheters or other problems like that, we need a larger, international study. I think one should be done because if you can prevent recurrences right away, which is what this study is suggesting, then that’s very good for these patients. We have ways of dealing with this afterwards, but it would be nice to prevent it right way. So given the fact that we already have five studies suggesting some benefit with this type of treatment, we should move into a large randomized study,” she recommended.

A session attendee noted that although colon cancer most commonly recurs in the liver, rectal cancer most commonly recurs in the pelvis. “Therefore, chemoradiotherapy is the standard of care now [for rectal cancer]. So infusional arterial chemotherapy should be used in patients with colon cancer, I think,” he said.

The patients with rectal cancer received radiation therapy after surgery if needed, Dr. Xu replied. “In the future, we will do subgroup analyses for colon cancer and for rectal cancer,” he added.

In the trial, patients from five hospitals in China were randomized to immediate curative primary surgery or to hepatic and regional arterial chemotherapy – floxuridine (FUDR), mitomycin C, and oxaliplatin delivered to both the main tumor-supplying artery and to the common hepatic artery – followed by curative primary surgery a week later. All patients received the same adjuvant therapy.

In the intention-to-treat population, estimated 5-year disease-free survival, the trial’s primary endpoint, was 75% with preoperative arterial chemotherapy versus 61% without it (hazard ratio, 0.60; P less than .001), reported Dr. Xu, who disclosed no relevant conflicts of interest. Subgroup analyses indicated that the benefit was significant in patients with stage III disease (68% vs. 51%; HR, 0.62; P = .017) but showed only a trend in patients with stage II disease (84% vs. 74%; HR, 0.64; P = .068).

Patients in the arterial chemotherapy group also were less likely to develop liver metastases (8% vs. 18%; HR, 0.39; P less than .001) and had better overall survival (81% vs. 72%, HR, 0.59; P = .003). But subgroup analyses again showed that benefit was significant only in the stage III patients.

Efficacy findings were similar in the trial’s eligible population, which excluded patients who were found to have pathologic stage I or IV disease at surgery and patients who developed metastases within 6 months of surgery.A total of 25% of patients in the arterial chemotherapy group experienced grade 3 toxicity from the procedure. However, the rate of postoperative complications did not differ significantly between the arterial chemotherapy and control groups.

SAN FRANCISCO – Giving preoperative chemotherapy directly into the tumor-feeding artery and prophylactically into the common hepatic artery to target any liver micrometastases improves outcomes in patients with early colorectal cancer undergoing curative resection. But benefit is seen mainly in patients with stage III disease.

These were among the key findings of the randomized multicenter phase III PHRAC trial (Preoperative Hepatic and Regional Arterial Chemotherapy) conducted among 688 patients in China with stage II or III colorectal cancer.

Compared with curative resection alone, followed by adjuvant systemic chemotherapy with the modified FOLFOX6 regimen, the addition of preoperative arterial chemotherapy reduced the 5-year estimated risks of disease-free survival events by 40%, of liver metastases by 61%, and of death by 41% in the trial population overall, according to data reported at the annual Gastrointestinal Cancers Symposium cosponsored by the AGA Institute, the American Society of Clinical Oncology, ASTRO, and the Society of Surgical Oncology. But stratified analyses showed that these benefits were significant only among the patients with stage III disease.

“Preoperative hepatic and regional arterial chemotherapy had no effect on colorectal cancer surgery or postoperative morbidity,” commented lead investigator Jianmin Xu, an oncologist at the Zhongshan Hospital, Fudan University, in Shanghai. This therapy “is safe and feasible and can reduce liver metastasis and improve disease-free survival and overall survival, especially for the stage III patients.”

“Dr. Xu’s study was a positive study, but we have no description of the catheter problems or the number of patients who could be treated,” commented invited discussant Dr. Nancy E. Kemeny of Memorial Sloan-Kettering Cancer Center, New York. Additionally, outcomes in the control group fell short of those seen in patients treated with FOLFOX historically.

Despite accumulating evidence of benefit, the procedure is not yet ready for incorporation into routine care, according to Dr. Kemeny. “Since we don’t have a lot of information about the problems with the catheters or other problems like that, we need a larger, international study. I think one should be done because if you can prevent recurrences right away, which is what this study is suggesting, then that’s very good for these patients. We have ways of dealing with this afterwards, but it would be nice to prevent it right way. So given the fact that we already have five studies suggesting some benefit with this type of treatment, we should move into a large randomized study,” she recommended.

A session attendee noted that although colon cancer most commonly recurs in the liver, rectal cancer most commonly recurs in the pelvis. “Therefore, chemoradiotherapy is the standard of care now [for rectal cancer]. So infusional arterial chemotherapy should be used in patients with colon cancer, I think,” he said.

The patients with rectal cancer received radiation therapy after surgery if needed, Dr. Xu replied. “In the future, we will do subgroup analyses for colon cancer and for rectal cancer,” he added.

In the trial, patients from five hospitals in China were randomized to immediate curative primary surgery or to hepatic and regional arterial chemotherapy – floxuridine (FUDR), mitomycin C, and oxaliplatin delivered to both the main tumor-supplying artery and to the common hepatic artery – followed by curative primary surgery a week later. All patients received the same adjuvant therapy.

In the intention-to-treat population, estimated 5-year disease-free survival, the trial’s primary endpoint, was 75% with preoperative arterial chemotherapy versus 61% without it (hazard ratio, 0.60; P less than .001), reported Dr. Xu, who disclosed no relevant conflicts of interest. Subgroup analyses indicated that the benefit was significant in patients with stage III disease (68% vs. 51%; HR, 0.62; P = .017) but showed only a trend in patients with stage II disease (84% vs. 74%; HR, 0.64; P = .068).

Patients in the arterial chemotherapy group also were less likely to develop liver metastases (8% vs. 18%; HR, 0.39; P less than .001) and had better overall survival (81% vs. 72%, HR, 0.59; P = .003). But subgroup analyses again showed that benefit was significant only in the stage III patients.

Efficacy findings were similar in the trial’s eligible population, which excluded patients who were found to have pathologic stage I or IV disease at surgery and patients who developed metastases within 6 months of surgery.A total of 25% of patients in the arterial chemotherapy group experienced grade 3 toxicity from the procedure. However, the rate of postoperative complications did not differ significantly between the arterial chemotherapy and control groups.