BATTLE to personalize lung cancer treatment
2010; Wiley; Volume: 116; Issue: 14 Linguagem: Inglês
10.1002/cncr.25493
ISSN1097-0142
Autores Tópico(s)Cancer Genomics and Diagnostics
ResumoA lung cancer clinical trial that analyzes patient biomarkers in tumor biopsies is guiding the field to more personalized treatment of the disease, according to the trial's principal investigator. Edward Kim, MD, associate professor of thoracic/head and neck medical oncology at the University of Texas M. D. Anderson Cancer Center in Houston, Texas, presented findings from the trial this pastApril at the American Association for Cancer Research Annual Meeting in Washington, DC. The Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) clinical trial used an innovative statistical model to match 4 drugs with specific biomarkers in the tumors of 255 patients with stage W non-small cell lung cancer who had received between 1 and 9 previous treatments. “This has never been done in lung cancer before,” Dr. Kim says. “What's generally done in lung cancer is we go back retrospectively in a lot of different trials and then grab the tissues after we've already got the results. You would never do that in hormonal studies in breast cancer. You want to collect tissue in real time so you can help drive therapy.” The phase 2 BATTLE trial proved it could be done, he notes. Often with lung biopsies, the tissue is inadequate to even make a good histological diagnosis. Approximately 15% to 20% of patients with lung cancer, for example, have cancers that are classified as non-small cell, not otherwise specified, Dr. Kim says. For BATTLE, the patients, who had already received chemotherapy, underwent core needle biopsies, in which a larger amount of tissue is gathered than with traditional fine-needle aspiration. Within 2 weeks, the researchers used the sample to determine the patients' biomarkers and used that information to place patients in 1 of the 4 treatment arms. “We can't be so naive to think that tumor biomarkers don't change after chemotherapy, so real-time biopsies are what we should be doing,” Dr. Kim says. “Also, we should have higher standards for the type of biopsy that is done when patients are originally diagnosed, so that we can conduct mutational testing. He adds that the scientific community was excited to see that a trial such as this (which randomized 255 patients in a single center and mandated biopsies) could be accomplished in fewer than 3 years. BATTLE is part of a federally funded program that began in 2000, and the trial was launched in 2005. For the study, researchers selected the drugs and biomarkers that they knew to be promising that time. The drugs used for the trial were erlotinib (Tarceva), sorafenib (Nexavar), vandetanib (Zactima), and erlotinib with bexarotene (Targretin). Each drug is designed to target specific molecular pathways, and currently none has a validated biomarker to guide its use. BATTLE's endpoint was disease control at 8 weeks, which recent research has found to be a good indication of overall survival. Among the findings were that 61% of patients with a K-RAS mutation in their tumors who were treated with sorafenib achieved disease control at 8 weeks compared with just 32% of those patients who were treated with the other 3 drugs. However, sorafenib performed poorly in patients with vascular endothelial growth factor receptor overexpression. Because those patients fared better with vandetanib, they were withdrawn from sorafenib treatment. BATTLE clinical trials are investigating personalized care for lung cancer. The first phase 2 BATTLE trial proved that tissue can be collected in real time to help drive therapy. Researchers obtained larger biopsy samples for the trial than are generally taken for diagnosis. Among the findings were that 61% of patients with a KRAS mutation had better disease control with sorafenib than with the other 3 drugs being tested. Future BATTLE trials that are to begin shortly will test different combinations of drugs as well as first-line therapy that combines chemotherapy with biologic agents. This is just 1 example of the trial's adaptive randomization approach, which incorporated information gathered earlier in the trial to guide treatment for newer patients. The latter group received a drug that had worked for previous patients with the same tumor hiomarkers At the same time, researchers identified patients who should not receive particular drugs. “Our role is not to take this data and open a phase 3 study, but to do these innovative biomarker-based studies and then get our findings to cooperative groups and industry and let them take it from there:' Dr. Kim says. Other departments at the University of Texas M.D. Anderson Cancer Center, including disease specialists in neuro-oncology, melanoma, and gastroenterology, have adopted BATTLE's platform for similar biomarker studies of their own, he notes. Meanwhile, Dr. Kim and his colleagues are preparing to initiate both BATTLE 2 and BATTLE 3 studies. The former, conducted in the same population of patients who have already been treated with chemotherapy, will test different combinations of drugs. It also will be conducted in 2 stages to provide more flexibility in allowing researchers to integrate new, promising biomarkers into the study. BATTLE 3 will assess first-line therapy, combining chemotherapy with biologic agents.
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