For Lung Cancer, "Tissue is the Issue"

EGFR levels predict if combined chemotherapy will benefit advanced NSCLC patients

/ Author:  / Reviewed by: Joseph V. Madia, MD

November is Lung Cancer Awareness Month. For many scientists, the future of lung cancer treatments lies within the tissue of the patients.

The Tissue is the Issue

Personalized care is an important step in fighting lung cancer. Cancer is complex and uses many functions of the human body against itself. Scientists are trying to identify how cancer works on a genetic level.

According to Dr. Fred Hirsch, M.D., Ph.D., professor of Medicine and Pathology and associate director for International Programs at the University of Colorado Cancer Center, genetics and our tissues hold the key to better treatments. Dr. Hirsch tells dailyRx, "We are moving away from a “one size fits all” for medicine. There is no singular way to treat cancer. Every individual is unique and as such, so should the treatment.

Inside our tissue there are ways to predict treatment response but as Dr. Hirsch says, "We need to discover new predictive markers. We already have discovered certain molecular features which predict better outcome to certain therapies but we will continue to find more of these predictive features."

Dr. Hirsch believes the patient can play an important role in lung cancer research. As Dr. Hirsch says, "the tissue is the issue and what I mean by that is that it's important that patients make tissue available for further studies. What we hope for is in the future the patient understands the importance of doing what we call molecular testing before treatment starts but we need to have patients give more tissue available for those studies."

Recent research has helped uncover some exciting developments that can tailor treatment to the individual, not the disease.

Lung Cancer is Risky Business

According to the National Cancer Institute, 221,130 new cases of lung cancer will be diagnosed in 2011 while 156,940 people will die from lung cancer. As troubling as those numbers are, an even greater concern is how progressive lung cancer is.

During 2001 to 2007, 56 percent of lung cancer that was diagnosed had already spread to other parts to the body. Survival within 5 years of diagnosis is just below four percent for advanced lung cancer patients whose cancer has spread to other parts of the body. Even when the cancer does not spread outside of the lungs, patients have a 52 percent chance of survival.

The overall survival rates was at 15.6 percent for all types of lung cancer.

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Close to 87 percent of all lung cancers are NSCLC. NSCLC spreads slowly and early stages of NSCLC have next to no symptoms so early detection can be problematic.

With so many new cases of lung cancer already being in an advanced stage, it tends to be difficult to treat as the low survival rate shows. There is a possibility that a treatment may fail but if there was a way to predict which patient will benefit from a certain therapy, there is an increased chance of survival.

Being able to predict what treatments can benefit certain patients and tailoring a treatment to an individual may let patients live longer or quite possibly cure the disease. In order for that to happen, new indicators of lung cancer are needed.

FLEXing A Way to Predict Treatment Response

Dr. Hirsch and his colleagues at the University of Colorado, first developed the First-Line Erbitux in Lung Cancer (FLEX) study in 2003. It highlights the importance of using levels of Epidermal Growth Factor Receptor (EGFR) as a way to predict treatment response.

EGFR is a molecule found on the surface of the Epidermal Growth Factor, a substance that plays a role in cellular development. A change or mutation affecting EFGR has been linked to the development of cancer.

In 2009 the FLEX randomized trial determined that Erbitux and chemotherapy had improved survival in patients with advanced lung cancer. Erbitux is an EGFR blocker that has been used to treat colon cancer, as well as head and neck cancer.

One recent study by researchers from the Medical University of Vienna is shining a light on predicting treatment response using FLEX.

Using FLEX Practically

Scientists have discovered that advanced NSCLC patients with high levels of EGFR were more receptive to a combination of Erbitux and chemotherapy. NSCLC patients treated with this combined therapy had a better survival rate than NSCLC patients treated with only chemotherapy.

As Dr. Hirsch says, "By using this scoring system to assess this protein, you split the patients between high, low or no level of expression by the FLEX system we published in 2003. If you fall into the high group, which included 25 percent of advanced NSCLC patients, this particular study showed that by combining chemo with an antibody against EGFR reduced the risk of death."

Identifying a group of patients that can benefit more from a chemo treatment using EGFR levels has scientists optimistic about future research. Dr. Hirsch sums up the findings by stating that, "Now, we have this large FLEX study where patients were treated with Erbitux in combination with chemotherapy, and the group of patients with high EGFR protein expression derive a significant benefit from this treatment combination in terms of overall survival benefit. This is another example of how we can use molecular testing to identify subgroups of patients who derive significant benefit from certain cancer therapies!"

The future for Lung Cancer Treatments

This is not the end of investigating EGFR expression. Dr. Hirsch concludes, "In my opinion a prospective validation of the data is warranted, and that will be happening in the large ongoing prospective study (SWOG 0819), which will include 1,500 patients. The results are very encouraging- and all the patients with lung cancer out there (today about 220,000 new cases of lung cancer per year in the US! ) need desperately some encouraging treatment improvements."

Personalizing medicine can lead to oncologists selecting the best possible treatment for a patient. Dr. Hirsch is optimistic about the future of lung cancer treatments, "I consider the new results very encouraging and hopefully the prospective validation studies will confirm the new FLEX results- this will be significant steps towards personalized medicine in lung cancer."

The study was published in the November edition of The Lancet.

Review Date: 
November 3, 2011