BATTLE trial personalizes lung cancer treatment

Study makes first step toward genome-based chemotherapy

WASHINGTON — Researchers have taken a step toward personalizing the treatment of lung cancer.

Matching treatments to specific mutations in tumors is routine for some cancers, such as breast cancer, but until recently, chemotherapy for lung cancer has been given on a one-treatment-fits-all basis. Now, a new study, called the BATTLE trial, shows that treatments tailored for each patient’s particular type of lung cancer may improve outcomes.

Results of the Phase II trial, the first large clinical trial to test the effectiveness of a personalized approach to lung cancer, were presented April 18 during the annual meeting of the American Association for Cancer Research.

Lung cancer is the leading cause of cancer death in the United States, killing more people than breast cancer, prostate cancer and several other types of cancer combined. “This war is something we’ve been losing for a long time using the traditional methods of chemotherapy,” said Edward S. Kim, an oncologist at the University of Texas M.D. Anderson Cancer Center in Houston and one of the coleaders of the trial.

More than 300 lung cancer patients with stage IV non–small cell lung cancer were enrolled in the trial. The patients had previously failed to respond to other types of chemotherapy. Even some patients whose cancer had spread to their brains participated.

“We were including lung cancer patients with the worst prognoses,” Kim said.

Biopsies of the patients’ tumors were analyzed for mutations or molecular changes in four different pathways that affect growth of tumor cells; 255 patients were then randomly assigned to take one of four different drugs specifically targeting the pathways.

Of the four drugs — erlotinib (also known by the brand name Tarceva), sorafenib (Nexavar), vandetanib (Zactima) and bexarotene (Targretin) — only erlotinib has been approved by the FDA for use against lung cancer.

At first, equal numbers of patients were assigned to each therapy. But as results from the first patients became available, the researchers used what they learned to assign subsequent patients to therapies more likely to work for their particular tumor type. The strategy had “limited success,” Kim says.

Overall, 46 percent of patients had their disease in check after eight weeks of treatment, meaning that their tumors had not grown significantly or had shrunk. That compares with 30 percent of late-stage lung cancer patients with controlled disease after eight weeks on traditional chemotherapy. Median overall survival for patients in the BATTLE trial was nine months, with 38 percent of patients surviving at least one year. Patients whose disease was under control after eight weeks of treatment had a median survival time of more than 11 months, while those who disease was still progressing after eight weeks of treatment survived about seven months, Kim says.

Each drug was found to do best against tumors associated with specific types of molecular changes. For instance, sorafenib was effective for 61 percent of people who had mutations in the KRAS gene, but people who had mutations in the EGFR gene actually had a worse outcome, the study suggested. Based on these promising results, sorafenib in particular is worthy of further study, said Paul Bunn, of the University of Colorado Cancer Center in Aurora, who presented a critique of the BATTLE study after Kim’s presentation.

Erlotinib worked best against tumors with EGFR mutations, while vandetanib was most effective for people who had high levels of VEGFR-2 protein in their tumors. A combination of erlotinib and bexarotene was most effective for people with defects in the Cyclin D1 pathway or who had extra copies of the EGFR gene in their tumor cells.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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