Gefitinib Extends Survival in Some Esophageal Cancers

Gefitinib (Iressa; AstraZeneca), an EGFR inhibitor used to treat non–small cell lung cancer, may extend overall survival in some patients with esophageal cancer. According to data from a small phase III clinical trial, patients who took gefitinib and had tumors with EGFR copy-number gain survived several months longer on average than patients without EGFR duplicates.

“We've long been waiting for a report like this,” says medical oncologist Igor Astsaturov, MD, PhD, at the Fox Chase Cancer Center in Philadelphia, PA, who treats patients with advanced esophageal cancer but did not work on the study. “It highlights the importance of personalizing oncology and analyzing the genetic makeup of individual tumors.”

Medical oncologist Russell Petty, MB, PhD, from the University of Aberdeen in Scotland, the trial's lead researcher, presented the findings in November at the 2014 National Cancer Research Institute's Cancer Conference in Liverpool, UK.

Petty and his colleagues studied tumor samples from 295 deceased esophageal cancer patients in a phase III trial called COG. The patients had received either gefitinib or a placebo after initial chemotherapy had failed. Results from the COG trial, published in The Lancet Oncology in July, suggested that, in general, gefitinib offered no survival benefit compared with placebo in patients with esophageal cancer.

However, in TRANS-COG, the translational research extension of the trial, Petty and his team analyzed outcomes for 48 patients—about one in six—whose tumor cells carried extra copies of EGFR. During the COG trial, 26 of those patients received gefitinib, and 22 received a placebo. Compared with those taking a placebo, patients who received gefitinib had a significant survival advantage at 3, 6, 9, and 12 months. After one year, an estimated 13% of the patients taking gefitinib were still alive, compared with none who had taken a placebo. Additionally, patients without extra copies of EGFR who took gefitinib did not derive any survival benefit from the drug.

“What's remarkable about this trial is that they looked retrospectively at all the patients on the COG trial and realized that those who had amplification of EGFR were the ones who were responsive to the treatment,” says Astsaturov. “By knowing genetic subtypes, we can choose appropriate therapies.”

Petty says EGFR copy gain may be used as a predictive biomarker for treatment, and that some patients with the disease may be sensitive to gefitinib. The next step, he says, is to determine whether the survival benefit associated with gefitinib increases when the drug is offered as first-line or adjuvant treatment, which is the goal of a prospective study he and his colleagues are planning now.