(ChemotherapyAdvisor) – Gefitinib extends progression-free survival (PFS) and improves quality-of-life (QOL) in patients with esophageal cancer who have relapsed after first-line chemotherapy, the first phase 3 trial to address the need for second-line treatments reported during the European Society for Medical Oncology, Vienna, Austria, has found.

Currently, no treatments have been shown to prolong survival or improve QOL in patients with esophageal cancer, reported Prof. David Ferry of New Cross Hospital in Wolverhampton, UK.

While the Cancer Oesophagus Gefitinib (COG) study did not reach its primary end point of overall survival (OS)—median OS was 3.73 months in the gefitinib arm and 3.60 months in the placebo arm (HR 0.90; 95% CI 0.74–1.09; P=0.285)—the study in 450 patients found that median PFS was 49 days for those administered gefitinib vs 35 days for the placebo arm (HR 0.795; 95% CI 0.66–0.96; P=0.017). Gefitinib also significantly improved odynophagia (P=0.004) as well as dysphagia, two important indicators of QOL.

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At 8 weeks, disease control rate in patients with measurable disease was 25.5% for gefitinib and 16.0% for placebo (P=0.014).

Adults with metastatic esophageal or types I/II junctional adenocarcinoma or squamous cell carcinoma who had disease progression after first-line treatment with up to two prior chemotherapy regimens were randomly assigned to gefitinib 500mg or placebo between March 2009 and November 2011 at 51 UK centers. Median age of the patients was 64 years and 83% were male. A total of 76% had adenocarcinoma and 78%, esophageal cancer.

Performance status (PS) was found to be a highly significant prognostic factor for both PFS (median PFS was 1.8 months for PS0 patients; 1.4 months for PS1, and 1.0 months for PS2) and OS (median OS was 6.0 months for PS0 patients, 3.9 for PS1, and 2.0 for PS2), Prof. Ferry reported, noting that “future studies should probably concentrate on PS 0/1 patients.”

The planned translational study, Trans-COG, will analyze biopsies from more than 300 patients to identify a molecularly defined subgroup where the benefit is enriched.

“If such a benefit can be identified, then given the good tolerance of gefitinib it could potentially be used in relapsed esophageal cancer,” Prof. Ferry said. “Do the responding patients have activating EGFR mutations like the super-responders in lung cancer? We don’t know yet but there would seem to be a dominant role for EGFR in a minority of esophageal patients.”

Abstract (scroll down to LBA20_PR)