For patients with non-small cell lung cancer and activating EGFR mutations who have had surgery, gefitinib appears to be more effective than chemotherapy in delaying disease recurrence. In a phase III trial, patients given the EGFR inhibitor were disease-free for 10 months longer than those who received chemotherapy.

For patients with non–small cell lung cancer (NSCLC) and activating EGFR mutations who have had surgery, gefitinib (Iressa; AstraZeneca) appears to be more effective than chemotherapy in delaying disease recurrence. The study findings will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, in June.

Approximately 25% of patients diagnosed with intermediate-stage NSCLC are eligible for surgery, said Yi-Long Wu, MD, during a press briefing. Chemotherapy is the standard of care following tumor removal, but Wu and his colleagues at the Guangdong Lung Cancer Institute in China wondered whether those with EGFR-mutant disease—about 30% of this population—would benefit from gefitinib, an EGFR inhibitor, instead.

To find out, the investigators enrolled 222 patients, all with EGFR mutations, in a phase III trial, ADJUVANT. Participants were randomly assigned to receive gefitinib daily for 2 years, or vinorelbine plus cisplatin every 3 weeks, for up to four treatment cycles.

Wu reported that for patients given gefitinib, the median time to recurrence was 28.7 months, versus 18 months for those in the chemotherapy arm. The 3-year disease-free survival rates were 34% and 27%, respectively. Gefitinib was well tolerated overall, with rash and elevated liver enzymes being the most common side effects.

“We think adjuvant gefitinib should be considered an important option for patients with intermediate-stage EGFR-mutant lung cancer,” Wu concluded.

Bruce Johnson, MD, chief clinical research officer at Dana-Farber Cancer Institute in Boston, MA, observed that in the United States, erlotinib (Tarceva; Genentech) is a more widely used EGFR inhibitor for NSCLC. Gefitinib got the FDA's nod in 2003 as a third-line therapy; however, approval was withdrawn in 2005 based on negative data from a confirmatory phase III trial. It was not known then that gefitinib is effective only against the disease's EGFR-mutant subtype, Johnson explained. In 2015, the FDA once again approved gefitinib, this time as first-line therapy for patients with metastatic disease and activating EGFR mutations.

“One reason why gefitinib showed broad activity in this study may be due to the fact that EGFR mutations are two to three times more frequent in people from East Asia—China, Korea, Japan—compared with Europeans,” Johnson commented. ADJUVANT's results are encouraging, he said, but longer follow-up is needed to determine if gefitinib also improves overall survival.

“I think many physicians will now evaluate lung tumors for EGFR mutations right after surgery, which isn't standard practice in the U.S.,” said Richard Schilsky, MD, chief medical officer at ASCO. “Typically, such testing doesn't take place until the disease recurs or turns metastatic.”

Even if treatment with an EGFR inhibitor is an option post-surgery, “keep in mind that we're talking about 2 years of gefitinib versus 12 weeks, at most, of chemotherapy,” Schilsky added. “It's a big commitment on the part of patients, and it also costs more. Basically, there's a lot to be considered here, and much will depend on whether gefitinib actually yields a survival advantage.”

Wu and his colleagues plan to answer this question in a follow-up analysis. They have also built a repository of lung tumor samples from ADJUVANT, which they will examine for additional biomarkers of gefitinib response or resistance. –Alissa Poh