Comparing Second-Line Therapies for Advanced Lung Cancer
Name of the Trial
Phase III Randomized Study of Pemetrexed Disodium Versus Erlotinib Hydrochloride As Second-Line Therapy in Patients with Advanced Non-Small Cell Lung Cancer (NCCTG-N0723). See the protocol summary.
Dr. Alex Adjei, NCCTG; Dr. Martin Edelman, CALGB; Dr. David Carbone, ECOG; Dr. Fred Hirsch, SWOG; and Dr. Geoffrey Liu, NCIC-CTG
Why This Trial Is Important
Advanced non-small cell lung cancer (NSCLC) remains a very difficult disease to treat, with most patients dying within a few years. Nevertheless, some advances in treatment are occurring. The chemotherapy drug pemetrexed can prolong survival in some patients and is a standard second-line treatment for patients with progressive or recurrent NSCLC following initial chemotherapy. The targeted drug erlotinib has also helped some patients with advanced NSCLC live longer and is FDA-approved for this use.
Erlotinib targets a protein called EGFR, which is found in abundance in some cancers and is thought to promote cancer cell growth. In contrast, pemetrexed inhibits cancer cell growth by interfering with DNA synthesis.
Some researchers have proposed that patients who have extra copies of the gene that makes EGFR (a phenomenon known as EGFR gene amplification) may be more likely to benefit from erlotinib than patients without such gene amplification. The only way to determine this for certain, though, is to carry out a randomized clinical trial comparing the effects of erlotinib with those of a standard drug in patients with and without EGFR gene amplification.
In this trial, patients with advanced NSCLC that has recurred or progressed after initial chemotherapy will be tested for EGFR amplification and then randomly assigned to receive either pemetrexed or erlotinib. Doctors want to see if patients with amplified EGFR fare better on erlotinib and whether those without amplified EGFR genes benefit more from pemetrexed. They will also measure the levels of other potential biomarkers of response to treatment, such as mutations in EGFR and in another gene, KRAS, and try to correlate them with response to these drugs.
"We're comparing two medications already approved and proven effective as second-line therapy for lung cancer, but what we want to know is: Can we tell by looking at the biomarkers whether one drug is better than the other for certain patients?" said Dr. Adjei.
"Until now, the way we've treated lung cancer is blindly," he added. "This is the first time we've had an opportunity to see if a test can help us tailor specific therapies for specific patients. Studies like this are absolutely crucial if we are to achieve the promise of personalized medicine for cancer care."
For More Information
See the Special Report from October 2008 for more about the gene testing in this trial.