By Scott Merville
Advanced lung cancer is notoriously bulletproof against secondline chemotherapy, but MD Anderson researchers are sharpening their aim at the disease by better aligning therapeutic weapons with tumor targets.
They’ve completed the first lung cancer clinical trial to guide treatment of patients based on their tumors’ molecular characteristics, a step toward personalized care and more effective, efficient clinical trials for new drugs. The study used an innovative statistical model to match four drugs to specific molecular signatures, or biomarkers, in the tumors of 255 stage IV non-small cell lung cancer patients who had received between one and nine previous treatments.
“New drugs that target molecular pathways help a small percentage of lung cancer patients, but right now there’s no way to determine who those patients are before treatment,” says Edward Kim, M.D., associate professor in MD Anderson’s Department of Thoracic/Head and Neck Medical Oncology and principal investigator on the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) clinical trials.
“Our goal is to make treatment of lung cancer, which kills more people than any other type of cancer, more like breast cancer, where validated tumor biomarkers guide treatment decisions and prolong survival,” Kim says.
First forays add to knowledge
The Phase II trial found evidence that each of the four drugs targets specific molecular defects better than the other three. Trial drugs were erlotinib (Tarceva®), sorafenib (Nexavar®), vandetanib (Zactima®) and erlotinib with bexarotene (Targretin®). Each is designed to block specific molecular pathways; none has a validated biomarker to guide its use.
The study found that 61% of patients with a KRAS mutation in their tumors who took sorafenib had disease control at eight weeks, compared with 32% of those who took the other three drugs. Tumors with KRAS mutations are highly resistant to treatment.
Overall, 46% of patients on the trial had disease control at eight weeks, compared with a historical experience of 30%. Median overall survival was nine months, and 38% survived to one year.
Future BATTLE trials will test drug combinations and single agents in other lung cancer settings, including frontline therapy. Ultimately, the researchers plan to try the approach in prevention clinical trials.
Reported in April at the 101st annual meeting of the American Association for Cancer Research.