NCI Launches First-Ever Study to Determine if Biomarkers Can Help Guide Treatment for Lung Cancer

A large, national clinical trial for non-small cell lung cancer has been launched to validate whether a biomarker can predict clinical benefit in the treatment of this disease.

Biomarkers, which are molecules found in the body that can signal an abnormal process or disease, would identify a target, known as epidermal growth factor receptor (EGFR). This receptor can be increased in some lung cancers due to the presence of extra copies of its coding gene. These extra copies can result in activation of tumor growth, so drugs that block this activation could have a significant impact on lung cancer treatment.

This study, sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, is called MARVEL (Marker Validation for Erlotinib in Lung Cancer) and will attempt to definitively establish the future value of selecting patients for treatment based on the presence or absence of EGFR activation.

Approximately 1,200 lung cancer patients will be tested for the status of this biomarker, and then will be randomly assigned to treatment based on the test results. Both EGFR-positive and EGFR-negative patients will receive either the chemotherapy drugs erlotinib (Tarceva, Genentech) or pemetrexed (Alimta, Eli Lilly) after they have received their initial, standard chemotherapy. Erlotinib specifically targets EGFR, whereas pemetrexed blocks tumor cell growth by another mechanism.

It is hypothesized that erlotinib will be superior in the patients with EGFR-positive lung cancer, whereas pemetrexed would be favored in patients with EGFR-negative lung cancer, based on knowledge from earlier, smaller studies.

MARVEL will incorporate genetic studies for erlotinib and pemetrexed that will be important to further identify patients with different sensitivity and toxicity profiles to these therapies.

Both erlotinib and pemetrexed are approved treatments for advanced NSCLC. Among the factors that appear to influence responsiveness to erlotinib, in addition to the level of EGFR activation, are whether the resulting cancer cells are classified as adenocarcinomas (as opposed to squamous or other types of cell), female gender, Asian ethnicity, and whether the patient was ever a smoker. However, no forward-looking study has been performed to definitively address which factors are most important.

MARVEL, also known as N0723, is a phase III study that will be led by the North Central Cancer Treatment Group (NCCTG) and include many other NCI-sponsored clinical trial groups.

The trial will enroll patients over a four year period and test them for EGFR status. It will randomly assign about 950 of the 1,200 tested patients to the treatment protocol, and, after a minimum of one to two years of follow-up, accrue data on disease-free and overall patient survival rates as well as determine if markers are good predictive and prognostic tools. It will also establish whether erlotinib provides a meaningful benefit over the patients' initial, standard chemotherapy.