This article is more than 5 years old. Information may no longer be current.
BATTLE: Biopsy-mandated study in NSCLC feasible
Success of the study should change the standard for conducting lung cancer studies, according to one expert.
Click Here to Manage Email Alerts
AACR 101st Annual Meeting
WASHINGTON, D.C. — Researchers at The University of Texas M.D. Anderson Cancer Center have successfully completed a biopsy-mandated study of patients with non–small cell lung cancer, providing evidence that novel biologic therapies can be successfully individualized based on a lung cancer patient’s tumor characteristics.
BATTLE — Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination — is a phase-2 hypothesis-driven study that identifies biomarkers to predict tumor response to help physicians tailor treatments.
“BATTLE is the first prospective biopsy-mandated
study that has been completed in lung cancer to our knowledge,” Edward
S. Kim, MD, told HemOnc Today. “That is an important step
toward personalizing therapy for lung cancer patients.” 
Click
here to hear Dr. Kim discuss the BATTLE results.
Kim, who presented the results at the American Association for Cancer Research 101st Annual Meeting in Washington, D.C., said this study should change the standard of how lung cancer trials are designed moving forward.
Upfront tissue samples
Through the BATTLE Program, M.D. Anderson Cancer Center’s thoracic program currently tests all enrolled patients for mutation status in its thoracic molecular pathology research lab. Tissue is biopsied in all patients upfront, then treatment is selected to best suit that patient’s profile.
“In a trial like BATTLE, we can test what markers we think may be important, treat them with their matching drugs and look at their outcomes,” Kim said in an interview. “All the outcomes are not great, but some of them are intriguing.”
Kim and colleagues enrolled more than 300 patients in less than three years. All patients were required to undergo fresh core needle biopsy upfront to allow researchers to test for 11 biomarkers: epidermal growth factor receptor, KRAS, BRAF mutation by polymerase chain reaction; EGFR and cyclin D1 copy number by fluorescence in situ hybridization; and VEGF, VEGF receptor, three retinoid X receptors and cyclin D1 by immunohistochemistry.
Based on these analyses, 255 patients were randomly assigned treatment. Treatments included once daily 150-mg/m2 erlotinib (Tarceva, OSI); twice daily 400-mg sorafenib (Nexavar, Bayer); once daily 300-mg vandetanib; or 150-mg erlotinib plus 400-mg/m2 bexatrone. The primary endpoint was disease control at eight weeks.
Improved outcomes
The overall disease control rate for all patients was 46% with a one-year survival of 39%. Median OS was nine months and PFS was 1.9 months, the researchers reported.
Patients identified as having an EGFR mutation had improved disease control rate when treated with erlotinib.
“With erlotinib, in the EGFR mutation subgroup, we saw 71% disease control. However, what we also saw with erlotinib is that it did not work well in the KRAS group,” Kim said.
Instead, patients with KRAS mutations responded better to treatment with sorafenib compared with any of the other treatment regimens (P=.011).
The overall disease control rate for patients assigned sorafenib was 58%, but an exploratory analysis of those patients with just KRAS mutations showed a disease control rate of 79% on sorafenib, according to Kim.
In addition, those patients with increased cyclin D1 immunohistochemistry positive (P=.011) and EGFR fluorescence in situ hybridization amplification (P=.006) had improvement disease control when treated with the combination of erlotinib and bexatrone.
An increase in VEGF receptor-2 immunohistochemistry was associated with improved disease control rate when treated with vandetanib (P=.05).
Finally, patients whose tumors had absence of EGFR mutations (P=.012) or high polysomy (P=.048) had improved disease control with sorafenib.
“The beauty of it is that whether or not they are great outcomes, we can go back to the tissue that we have gathered and test numerous other markers or profiles to try and figure out what is going on in each patient’s tumor and how it reacts to certain drugs. That is unprecedented,” Kim said. – by Leah Lawrence
As we take each small baby step forward [in lung cancer research] we understand that there is a ceiling that we have hit with chemotherapeutic agents and if we are to make significant strides in the care of lung cancer patients. We need to identify unique genetics in specific subsets of patients and develop personalized, targeted therapies that target those individual subsets of patients. That was the primary goal of the BATTLE trial. I laud Drs. Kim and Herbst and their colleagues at M.D. Anderson for accomplishing what was a major feasibility question.
- Deepa Subramaniam, MD
Interim Chief, Center for Thoracic Medical Oncology, Georgetown University Lombardi Cancer Center
For more information:
- Kim E. #LB-1. Presented at: AACR 101st Annual Meeting; April 17-21, 2010; Washington, D.C. .
Follow HemOncToday.com
on Twitter.