Immune-boosting colorectal cancer drug shows promise

New data on an emerging treatment that aims to fight colorectal cancer by stimulating the immune system have been presented at the ESMO 15th World Congress on Gastrointestinal Cancer.

The findings confirm the biological action of the drug called MGN1703 and suggest it may be possible to identify which gastrointestinal cancer patients will benefit most from the treatment, reported Prof Hans-Joachim Schmoll from Martin Luther University, Halle, Germany.

MGN1703 is a small DNA molecule recognised by a receptor—called toll-like receptor 9—that is expressed in certain immune system cells. The drug is designed to broadly activate all components of the innate immune system to stimulate the destruction of cancer cells.

The new data come from the final analysis of the phase II IMPACT study, which investigated MGN1703 in 59 patients with metastatic colorectal cancer.

The IMPACT study was an international, randomised, double-blind trial that was conducted in patients who had achieved disease control after 4.5 to 6 months of chemotherapy.

Standard chemotherapy for patients with metastatic colorectal cancer who respond to treatment is often completely or partially discontinued until the disease progresses. It was during this ‘maintenance’ phase of treatment that the new drug was administered.

Immune-boosting COLorectal cancer drug shows promise Prof Schmoll and colleagues had intended to test the drug on 129 patients, but difficulties recruiting participants meant the trial was closed after 59 patients had been randomly assigned to either MGN1703 (43 patients) or placebo (16 patients).

“After a median follow-up of 17.3 months, MGN1703 prolonged profession-free survival from the start of induction as well as start of maintenance therapy, including four patients with sustained progression-free survival who are still on treatment,” Prof Schmoll says.

Colorectal Cancer Facts
The American Cancer Society estimates that in 2011 about
141,210 people will be diagnosed with colorectal cancer and
about 49,380 people will die of the disease in the US. In both
men and women, colorectal cancer is the third most commonly
diagnosed cancer and the third leading cause of cancer death.
The majority of these cancers and deaths could be prevented
by applying existing knowledge about cancer prevention and
by increasing the use of established screening tests. In the past
decade, there has been unprecedented progress in reducing
colorectal cancer incidence and death rates in most US population
groups; this progress has come about largely through the
prevention and early detection of colorectal cancer through
screening. Even more progress is possible by increasing access
to and utilization of colorectal cancer screening tests; currently,
only about half of people aged 50 or older, for whom screening is
recommended, report having received colorectal cancer testing
consistent with current guidelines.

Screening has the potential to prevent colorectal cancer because
most colorectal cancers develop from adenomatous polyps. Polyps
are noncancerous growths in the colon and rectum. Though most
polyps will not become cancerous, detecting and removing them
through screening can actually prevent cancer from occurring.
Furthermore, being screened at the recommended frequency
increases the likelihood that when colorectal cancer is present,
it will be detected at an earlier stage, when it is more likely to be
cured, treatment is less extensive, and the recovery is much faster.
In addition to following recommended screening guidelines,
people can reduce the risk of developing or dying from colorectal
cancer by maintaining a healthy body weight, regular physical
activity, limiting intake of red and processed meats, and by not

The American Cancer Society has identified colorectal cancer as
a major priority because the application of existing knowledge
has such great potential to prevent cancer, diminish suffering,
and save lives. This third edition of is part of the
Society’s effort to motivate the public and
medical communities to prevent the tragic and avoidable suffering
caused by colorectal cancer. It is intended to provide basic
information about colorectal cancer to the general public, the
media, and health professionals.

A pre-planned analysis of immune cell populations showed that the activation of a particular subset of immune system cells, called Natural Killer T Cells, appeared to potentially predict which patients might benefit, Prof Schmoll said.

Immune-boosting COLorectal cancer drug shows promise “We saw a significant increase of CD14+CD169+ monocytes in all but one of the MGN1703 treated patients but none of the placebo patients, which indicates the drug is having a biological effect,” he said.

“These data, presented at the 15th ESMO World Congress on Gastrointestinal Cancer for the first time, are showing a highly interesting trend which should be followed-up and confirmed in a larger study,” Prof Schmoll said.

Since treatment with immunotherapeutic drugs such as MGN1703 needs time to take effect, patients who have a lower tumour burden and a response to prior chemotherapy might be more likely to have a benefit of the treatment with MGN1703, Prof Schmoll said.

“The evidence we are presenting at the 15th ESMO World Congress on Gastrointestinal Cancer is the first to show an immune cell population that might also help identify patients with greater benefit from MGN1703. There is mounting evidence that patients who achieve a response with immunotherapy seem to have a very prolonged disease control. A large confirmatory trial is needed to confirm these interesting findings.”

Who gets colorectal cancer?
Anyone can get colorectal cancer. The lifetime risk of being
diagnosed with cancer of the colon or rectum is about 5% for both
men and women in the US.

Incidence and death rates for colorectal cancer increase with age.
Overall, 90% of new cases and 94% of deaths occur in individuals
50 and older. The incidence rate of colorectal cancer is more
than 15 times higher in adults 50 years and older than in those
20 to 49 years.

Overall, colorectal cancer incidence and mortality rates are
about 35% to 40% higher in men than in women (Table 1). The
reasons for this are not completely understood, but likely reflect
complex interactions between gender-related differences in
exposure to hormones and risk factors.

Gender differences in risk
patterns may also help explain why the proportion of colorectal
tumors occurring in the rectum is higher in men (31%) than in
women (24%).

Colorectal cancer incidence and mortality rates are highest in
African American men and women; incidence rates are
20% higher and mortality rates are about 45% higher than those in
whites. Incidence and mortality rates among other major racial/
ethnic groups are lower than those among whites.

It is important to recognize that the burden of colorectal cancer
also varies greatly within racial/ethnic groups. For example,
incidence rates among American Indians/Alaska Natives (AI/AN)
living in Alaska are 102.6 (per 100,000), compared to 21.0 among
AI/ANs residing in the Southwest.

Commenting on the findings, ESMO spokesperson Michel Ducreux, Head of the Gastrointestinal Unit at the Institut Gustave Roussy, Villejuif, France, said the new results are supporting the concept for this approach.

“This is an interesting and somehow promising drug which represents a new concept of maintenance therapy with immunomodulation,” he said. “The results in terms of progression-free survival and response were consistent, however based on a very small number of patients, and needs follow up and confirmation in a definitive confirmatory trial. “

Stage at Diagnosis

Unfortunately, the majority of colon cancers are not found early (before it has spread):

  39% of colon cancers are found while the cancer is found at a local stage (confined to colon or rectum).
  37% of colon cancers are found after the cancer is diagnosed at a regional stage (spread to surrounding tissue).
  20% of colon cancers are found after the disease has spread to distant organs.

Colon Cancer and Age

  90% of new cases and 95% of deaths from colon cancer occur in people 50 or older. However, colon cancer does not discriminate and can happen to men and women at any age.
  While rates for colon cancer in adults 50 and older have been declining, incidence rates in adults younger than 50 years has been increasing.
  Just launched! New pages with tons of information about young-onset colon cancer, who’s at highest risk and resources for you. Check them out!

Colon Cancer and Ethnicity and Race

  Jews of Eastern European descent (Ashkenazi Jews) may have a higher rate of colon cancer.
  Partly because of disproportionate screening, African-American men and women have a higher risk of developing colon cancer and a lower survival rate (about 20% higher incidence rate and 45% higher mortality rate) compared to Caucasians, Asians, Hispanics and Native Americans.
  The risk of death is also increased for Native Americans and Alaskan Natives.


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