Lilly Stomach Cancer Drug Prolongs Life in Colon Cancer Study

The gist: A drug used to treat stomach cancer may also help treat people with advanced colorectal cancer. The drug, called Cyramza, was tested in a clinical trial—a research study with volunteer patients. The trial involved patients who had not been treated successfully with other approaches.

“Eli Lilly and Co’s LLY.N Cyramza stomach-cancer drug prolonged survival of patients with advanced colon cancer in a late-stage study, the U.S. drugmaker said on Friday.

“Based on favorable data from the Phase III study, Lilly said it would ask regulators in the first half of 2015 to approve Cyramza in patients with colorectal cancer that has spread to other parts of the body. It plans to present detailed results from the trial at a scientific meeting next year.

“The 1,000-patient global study, called RAISE, involved patients who had previously failed to adequately benefit from Roche Holding AG’s ROG.VX Avastin and other standard treatments.

“Patients taking Cyramza along with chemotherapy showed a statistical improvement in survival, compared with those in the study who took a placebo and chemotherapy.”

MOLOGEN AG: Initiation of Phase III IMPALA Study with Immunotherapy MGN1703 in Colorectal Cancer

The gist: The first patient has been enrolled in a new clinical trial—a research study with volunteer patients. The goal of the trial is to test whether a new drug can keep cancer from returning (recurrence) in people who were treated for metastatic colorectal cancer. MGN1703 is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer.

“MOLOGEN AG has enrolled the first patient in the international IMPALA study. Primary objective of the phase III pivotal trial is to prove that a switch maintenance therapy with the cancer immunotherapy MGN1703 leads to an increased overall survival (OS) in patients with metastatic colorectal carcinoma.

“IMPALA is a randomized, international, multicenter and controlled phase III trial expected to recruit about 540 patients from more than 100 European centers in eight European countries, including the five major pharma markets. The primary endpoint is overall survival. Secondary study endpoints include progression-free survival, Quality of Life (QoL) as well as safety and tolerability.

“ We are pleased that we have already enrolled the first patient in the IMPALA trial. We are excited to learn more about the efficacy of the novel immunotherapy MGN1703,’ said Prof. David Cunningham, MD, Department of Medicine and Director of Clinical Research, Royal Marsden Hospital in London. ‘The trial aims to confirm the trend in overall survival along with very good safety and tolerability of MGN1703 as observed in the IMPACT trial.’ ”

Erbitux Edges Avastin for First-Line Colorectal Cancer Therapy

Editor’s note: This article discusses the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to compare two drugs—bevacizumab and cetuximab—when they were added to the standard chemotherapy combo FOLFIRI. All patients who participated in the trial had metastatic colorectal cancer. The researchers found that patients treated with FOLFIRI plus cetuximab had longer overall survival times that patients treated with FOLFIRI plus bevacizumab. The results differ from those from another recent study, which found no significant difference between the two treatments.

“Adding cetuximab (Erbitux) to the standard first-line FOLFIRI chemotherapy regimen resulted in longer overall survival compared with FOLFIRI plus bevacizumab (Avastin) in patients with metastatic colorectal cancer, according to results of the phase III FIRE-3 trial published this month in the Lancet.

“This result was seen in patients with a wild-type exon 2 KRAS gene. The longer overall survival was observed despite there being no significant difference in objective response between the two study groups.

“The study analyzed data from 592 patients with KRAS exon 2 wild-type colorectal cancer treated with FOLFORI and either cetuximab (an epidermal growth factor receptor inhibitor) or bevacizumab (an angiogenesis inhibitor). Patients were recruited at 116 Austrian and German cancer centers.”

Low-Risk Adenoma Removal Associated with Reduced Colorectal Cancer Mortality

Editor’s note: This article is about the results of a research study for colorectal cancer. The researchers looked at the medical records of people who had high- and low-risk adenomas removed to see which patients later died of colorectal cancer. They found that people who had high-risk adenomas removed were more likely to die of colorectal cancer within 8 years. People who had low-risk adenomas removed were no more likely to die of colorectal cancer than the general population. Based on the results, people who have low-risk adenomas removed might not need to undergo surveillance after surgery. Surveillance can involve invasive colonoscopies, so many of these patients might actually be better off without surveillance.

“Patients who had low-risk adenomas removed demonstrated lower rates of long-term colorectal cancer mortality than those who had high-risk adenomas removed, according to results of a population-based study.

“The low mortality rate associated with low-risk adenomas may obviate the need for post-colonoscopy surveillance in this population, researchers wrote.

“Magnus Løberg, MD, of the department of health management and health economics at University of Oslo, and colleagues used Norway’s cancer registry and cause of death registry to assess colorectal cancer mortality among 40,826 adults who had colorectal adenomas removed between 1993 and 2007.

“Patients with high-risk adenomas — or those with high-grade dysplasia, a villous component or a size ≥10 mm — underwent colonoscopy after 10 years, whereas those with three or more adenomas underwent colonoscopy after 5 years in compliance with Norwegian guidelines.”

Facts, Myths, and the Stool DNA Test

“Publicity surrounding the FDA’s approval of a stool DNA test for colorectal cancer screening made fact and fiction difficult to distinguish, according to Deborah Fisher, MD, MHS, a gastroenterologist and associate professor at Duke University in Durham, N.C. She wants to set the record straight in this guest blog.

“I am a gastroenterologist and much of my research and clinical focus is colorectal cancer screening. Some of my previous comments on the new stool DNA test, Cologuard, have already been published in the New York Times as well as on MedPage Today. However, I have recently noticed a number of misleading articles in various newspapers across the country and wanted to address these, likely common, misconceptions about the new test.

“First, I want to openly acknowledge the positives about Cologuard. The study in the New England Journal of Medicine examining its ability to find a colon or rectal cancer as a one-time test (compared to colonoscopy as the gold standard) was large, well-designed and well-executed. It showed that as a one-time test Cologuard was 92% sensitive for cancer. It also showed that the false positive rate was about 13%.

“The problem has arisen in how the study results are being spun. Here are a few emerging myths to debunk:”

Drug Shows Promise for Subset of Stage III Colon Cancer Patients

This article describes the results of a clinical trial—a research study with volunteer patients. The trial tested adding a third drug to a standard two-drug chemotherapy treatment for colorectal cancer. The standard treatment consists of the drugs fluorouracil and leucovorin. It is given to patients after tumor-removal surgery to keep the cancer from coming back (recurrence). In the trial, a third drug called irinotecan was added. The researchers found that stage III patients whose tumors tested positive for a genetic change called CIMP benefitted from the irinotecan addition. Stage III CIMP-negative patients did not.

“When added to the standard chemotherapy treatment — fluorouracil and leucovorin — adjuvant irinotecan therapy improved overall survival rates for patients with the CpG island methylator phenotype (CIMP). CIMP is seen in about 10 to 20 percent of colorectal cancers. Patients with CIMP-negative tumors, however, exhibited significant harm from the addition of irinotecan — overall survival was 68 percent compared with 78 percent for those receiving the standard treatment alone.

“Our results serve as an example that the molecular characterization of individual tumors may help to determine the most appropriate treatment for patients with colon cancer,” said lead study author Stacey Shiovitz, MD, from the department of medicine, University of Washington, Seattle, WA, and the clinical research division of Fred Hutchinson Cancer Research Center, also in Seattle. “Based on our findings, identification of a tumor’s CIMP status should play a greater role in the clinical setting.”

Higher Bar Set for Trials in Advanced Colorectal Cancer

Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to compare four different treatments for metastatic colorectal cancer (mCRC). All patients took a combination of chemotherapy drugs; either FOLFIRI [which combines folinic acid, fluorouracil and irinotecan] or FOLFOX [folinic acid, 5-fluorouracil and oxaliplatin]. Patients also took a targeted drug alongside the chemo; either bevacizumab (aka Avastin) or cetuximab (Erbitux). All four treatment combinations resulted in similar survival times—a median of 29 months. Compared to other clinical trials, this is a relatively long survival time. Based on these results, oncologists will now have more options for treating their patients according to patients’ preferences and side effects.

“Patients with KRAS wild-type metastatic colorectal cancer (mCRC) receiving first-line treatment with a chemotherapy backbone plus bevacizumab or cetuximab survived for a median of 29 months, the longest median survival time reported in a major trial of these severely ill patients.

“Importantly, survival times were the same, whether patients received the anti–vascular endothelial growth factor bevacizumab (Avastin, Genentech) or the anti–epidermal growth factor receptor (EGFR) cetuximab (Erbitux, Bristol-Myers Squibb), or whether they received FOLFOX or FOLFIRI, results from the long-awaited Phase III CALGB/SWOG 80405 trial showed.

“ ‘What this tells us is that either FOLFIRI [folinic acid, fluorouracil and irinotecan] or FOLFOX [folinic acid, 5-fluorouracil and oxaliplatin] with either bevacizumab or cetuximab are perfectly reasonable options,’ said Alan P. Venook, MD, the Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California, San Francisco.”

No Difference in Response Rate but Overall Survival Benefit With First-Line FOLFIRI/Cetuximab vs FOLFIRI/Bevacizumab in Metastatic Colorectal Cancer

Editor’s note: Researchers organized a clinical trial with volunteer patients to compare two treatments for people with metastatic colorectal cancer. All patients in the trial took a chemotherapy treatment called FOLFIRI. (FOLFIRI combines the drugs fluorouracil, leucovorin, and irinotecan.) Some of the patients were also given the drug cetuximab, and the rest took the drug bevacizumab along with FOLFIRI. The patients who took FOLFIRI plus cetuximab survived significantly longer than the patients who took FOLFIRI plus bevacizumab.

“In a European phase III FIRE-3 trial reported in The Lancet Oncology, Heinemann et al found no difference in response rate, the primary endpoint, between FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus the anti-EGFR antibody cetuximab (Erbitux) vs FOLFIRI plus the anti-VEGF-A antibody bevacizumab (Avastin) in first-line treatment of patients with metastatic colorectal cancer. The cetuximab-containing regimen was associated with a significant overall survival advantage…

“In this open-label trial, 592 patients with KRAS exon 2 codon 12/13 wild-type metastatic colorectal cancer aged 18 to 75 years from centers in Germany and Austria were randomly assigned between January 2007 and September 2012 to receive FOLFIRI plus either cetuximab (n = 297) or bevacizumab (n = 295). The primary endpoint was objective response in the intention-to-treat population. The study has completed recruitment, but patient follow-up is ongoing.”

FDA Approves DNA Screening Test for Colorectal Cancer

“Yesterday, the US Food and Drug Administration (FDA) approved the first DNA-based stool sample screening test for colorectal cancer. The new test, called the Cologuard test, was developed by Exact Sciences.

“The trial that led to the approval, which compared Cologuard to the fecal immunochemical test (FIT), included 10,023 participants. FIT is a commonly used screening test that detects blood in the stool and is also non-invasive.

“ ‘This approval offers patients and physicians another option to screen for colorectal cancer,’ said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health at the FDA’s Center for Devices and Radiological Health, in a press release. ‘Fecal blood testing is a well-established screening tool and the clinical data showed that the test detected more cancers than a commonly used fecal occult test.’

“In clinical testing Cologuard detected 92% of colorectal cancers and 42% of advanced adenomas. FIT detected 74% of cancers and 24% of advanced adenomas. The Cologuard test detects particular DNA mutations in stool samples that can be an early sign of cancer, and people who test positive for these are recommended for colonoscopies.”