Biomarkers Help Hit The Bull's-Eye

Results of the first lung cancer clinical trial to match targeted drug therapies to molecular signatures, or biomarkers, on tumors may offer promise for more effective treatment. The right match gave 46% of advanced cancer patients control over their disease within two months, compared with 30% for unmatched treatment.

University of Texas M. D. Anderson Cancer Center researchers presented the results last week at the American Association for Cancer Research meeting in Washington, D.C. They used statistical modeling to match one of four drugs to specific biomarkers in the tumors of 255 late-stage, non-small-cell lung cancer patients.

The novel approach could help improve clinical trial design and speed up drug development. In lung cancer, large randomized trials have been the norm. By selecting patients who might respond ahead of time, the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial points the way to quicker success in smaller, more precise trials.

“BATTLE is an important step toward personalized medicine and marks a paradigm shift for clinical trials by demonstrating the feasibility of a biopsy-based, hypothesis-driven biomarker trial,” says Roy S. Herbst, UT oncology professor and coprincipal investigator on the trial. The findings must still be validated in Phase III trials.

None of the four drugs tested—Tarceva, Nexavar, Zactima, and Targretin—has a validated biomarker to guide its use. But by analyzing tissue samples from an initial 97 patients, the study found that each drug targets specific molecular signatures better than the other three. Feeding this information back into the trial guided which drugs were assigned to new patients.

Ultimately, clinical researchers are working toward validated biomarkers that can be clearly interpreted through simple, accurate, and reproducible assays. Meanwhile, the BATTLE trial has shown that an adaptive trial design, especially one that overcomes the hurdle of having to collect biopsies, can work, explains Joseph R. Nevins, director of Duke University’s Center for Applied Genomics & Technology, who was not connected with the trial.

“We have the tools,” Nevins says, “and we have to be thinking about more efficient ways to evaluate drugs and move promising drugs forward.”