Small progress in treating lung cancers reported at European conference

SEATTLE – (Cancer Digest) – In a pair of studies presented at the Second European Lung Cancer Conference, held this week in Geneva, researchers confirm that specific molecular features of lung tumors are  key to identifying patients most likely to benefit from new targeted therapies such as erlotinib (Tarceva®) and gefitinib (Iressa®).

In a presentation by Dr. Robert Pirker of the Medical University of Vienna, Pirker noted that while such "personalized" therapies promise to improve survival, they will require a change in the way patients are diagnosed and assessed before treatment. It will require closer coordination between pulmonologists, pathologists, biologists and oncologists.

In the second presentation, Dr. David Carbone, of Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, and Canadian colleagues demonstrate a method of identifying patients who will benefit from such drugs when other methods of doing so are hampered by insufficient tissue samples available for testing.

Tailoring lung cancer therapy to individual

• New drugs require a change in clinical practice

GENEVA – April 30, 2010 – The recent approval of Europe's first personalized treatment for lung cancer heralds the arrival of a new era for lung cancer treatment that will demand significant changes to the way cancer specialists and other hospital doctors work, a leading expert said today at the 2nd European Lung Cancer Conference in Geneva, Switzerland.

"Recently, oral treatment with the targeted drug gefitinib was shown to be superior with regard to progression-free survival compared to treatment with up to six cycles of first-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) who have mutations in their tumors that activate a cell-surface molecule called epidermal growth factor receptor (EGFR)," Pirker said.

This finding led to the approval of this drug in Europe in 2009, but only for treating patients whose tumors carry these mutations.

"Before we can offer patients gefitinib, the presence of these mutations in tumor cells has to be clearly demonstrated," he explained.

In order to achieve this, doctors must perform a molecular analysis of tumor material from biopsies. "This will benefit patients, but it changes the whole diagnostic workup and requires some change in the thinking of oncologists, including closer cooperation between the various disciplines: interventional pulmonologists, pathologists, biologists, oncologists," he said.

Scientists around the globe are currently probing the genetics of cancers with the aim of identifying new targets for personalized treatment. These projects, such as the International Cancer Genome Consortium, mean that testing for mutations in tumors will become routine.

Eventually, tissue sampling to allow this kind of mutation testing will become standard in Europe, Pirker said. But currently, there are obstacles preventing it from becoming more widespread.

"The obstacles include the fact that too few doctors trained in invasive tumor sampling, that mutation analysis not yet readily available, and that there are reimbursement issues which might vary from country to country," he said.

If these obstacles can be overcome, and more doctors are trained in taking lung cancer biopsies, more patients will be able to be treated with oral gefitinib®, and the discovery of other new therapeutic targets will be accelerated," he said.

Blood test may identify which lung cancer patients benefits from erlotinib

• Test can be used to for patients who cannot be analyzed by current method

GENEVA – April 30, 2010 –Testing for the presence of specific cancer protein 'profiles' in the blood of lung cancer patients may be a useful means of identifying patients whose tumors are more likely to shrink when treated with the drug erlotinib, especially when other testing methods are unavailable, data from a new study shows.

Dr. David Carbone from Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, and Canadian colleagues presented the new findings at the 2nd European Lung Cancer Conference in Geneva, Switzerland today.

Erlotinib is one of a class of drugs that specifically inhibits an important cell-surface molecule known as the epidermal growth factor receptor (EGFR), which is highly expressed in some forms of cancer, including lung cancer. By blocking this receptor, drugs such as erlotinib aim to slow tumor growth and proliferation.

Carbone’s team analyzed blood samples from a large multi-center study that had been taken from patients before they started treatment in the study. They looked at the proteomic profile of the patients, which is a large complement of proteins. They looked for specific protein structures already known to predict outcomes in patients treated with EGFR-blockers. The found erlotinib improved survival compared to placebo in patients with advanced non-small-cell lung cancer who had already tried one or two other drugs.

They divided the protein profiles into two categories.  Those in the “good” category had several proteins known to be affected by erlotinib, while those with structures not expected to react to erlotinib were categorized as “poor”. They found that patients with the good proteomic profile were significantly more likely to respond to erlotinib.

"The bottom line is that the proteomic test – comparing 'good' and 'poor' profiles – was strongly prognostic (predictive) in both erlotinib and placebo arms," said Carbone. "Proteomics 'good' patients also had a significantly higher response rate than proteomics 'poor' patients (9.8% vs. 0.9%, p=0.002).

Carbone notes that this method of identifying those patients who are likely to respond to the drug is not as sensitive as other methods, but could be used when there is not enough biopsy tissue available for those methods.

The most common current method of identifying erlotinib-sensitive patients includes a technique called fluorescence in-situ hybridization or FISH to assess the prevalence of EGFR protein in a tumor sample. To get a accurate count, however requires enough tissue sample to obtain a statistically valid estimate of the protein presence.

"FISH overall was a better predictor of benefit, but can only be done with adequate biopsy tissue, which was available in this study only in 22 percent of patients. With the serum test, 99 percent of patients had a successful determination of proteomic status."

"Thus, I think this test may be of potential value in identifying a subgroup of patients with a good prognosis and who are likely to have response to erlotinib; it may be of particular value for those in whom tumor tissue is inadequate or unavailable," Prof Carbone said.