Gefitinib, also known as Iressa, the once-promising targeted therapy for the treatment of non-small cell lung cancer, has proven as effective as chemotherapy as a second-line therapy for the disease with far fewer side effects, according to an international Phase III clinical trial, led by researchers at The University of Texas M. D. Anderson Cancer Center.
However, in contrast to earlier Iressa findings, the study showed that there was no additional survival benefit for patients who expressed an elevated level of the epidermal growth factor receptor (EGFR) mutation.
The Iressa in Non-small cell lung cancer Trial Evaluating REsponse and Survival versus Taxotere (INTERST) study, published today in The Lancet, represents a paradigm shift for the treatment of the disease, according to lead author Edward S. Kim, M.D., assistant professor in M. D. Anderson's Department of Thoracic Head and Neck Medical Oncology. It marks the first time in lung cancer that an oral pill has proven as effective as chemotherapy in a head-to-head trial.
"This is the largest study in lung cancer comparing an oral biologic therapy to chemotherapy, and shows, for the first time, that an oral biologic therapy is just as effective as chemotherapy," said Kim, the study's corresponding author. "Based on our findings, I'm hopeful that Iressa can return as a treatment for lung cancer in the United States, offering this some patients a therapy with far fewer side effects."
The study also should offer both physicians and patients some confidence in another biological oral therapy, erlotinib, commercially known as Tarceva, that hits similar targets as Iressa and is commercially available for the treatment of lung cancer in the second line setting, explained Kim.
To best appreciate these findings, it's important to remember Iressa's history, said Kim. Iressa, a once-daily, oral tablet, was the first in a new class of anti-cancer drugs known as EGFR tyrosine kinase inhibitors (TKI) to become commercially available after two Phase II trials found the drug to be efficacious. Iressa was fast-tracked to the FDA and received approval May 5, 2003 as a single agent treatment for patients whose advanced lung cancer had continued to progress despite treatment with platinum-based and docetaxel chemotherapy.
However, in 2005, a large randomized lung cancer study reported that Iressa failed to significantly improve survival in patients with non-small cell lung cancer when compared to placebo. Ultimately, the drug's labeling was altered by the FDA; only cancer patients who had already taken the medicine and whose physicians believed it was helping them were allowed to receive the drug. No new lung cancer patients in the United States were given the drug after this time. However, Iressa remained an available therapy in other countries around the world.
Just prior to these negative findings, the INTEREST study began to enroll patients in 2004. Because of the negative data, INTEREST, an FDA-mandated study, was halted in the United States but continued in other parts of the world.