Gefitinib extended PFS in esophageal cancer

Issue: October 25, 2012

Gefitinib significantly improved quality of life and prolonged PFS for patients with metastatic esophageal cancer after chemotherapy, according to results of a phase 3 trial.

Perspective from Jean-Yves Douillard, MD, PhD

High EGFR expression is associated with poor outcomes in patients with esophageal cancer. Results of prior studies examining gefitinib (Iressa, AstraZeneca), an EGFR kinase inhibitor, have shown promise of improved survival in that patient population.

Currently, there are no standard therapies for patients with metastatic esophageal cancer who relapse after first-line chemotherapy.

In the Cancer Oesophagus Gefitinib (COG) trial — a double blind, randomized, placebo-controlled study — David R. Ferry, MB, ChB, professor of medical oncology at Russells Hall Hospital in Dudley, United Kingdom, and colleagues enrolled 450 patients with metastatic esophageal or types I/II junctional adenocarcinoma or squamous cell carcinoma that progressed after chemotherapy.

The patients were recruited from 51 United Kingdom centers between March 2009 and November 2011. The median patient age was 64 years.

The researchers randomly assigned patients to gefitinib 500 mg daily or placebo.

The median PFS for patients assigned to gefitinib was 49 days compared with 35 days for those assigned to placebo (HR=0.795; 95% CI, 0.66-0.96), study results showed.

Median OS was similar between the two arms (3.73 months for gefitinib vs. 3.6 months for placebo; HR=0.9; 95% CI, 0.74-1.09). The results did not reach the OS endpoint, according to investigators.

Patients assigned to gefitinib also had improved disease control rates at 8 weeks (25.5% vs. 16%; P=.014).

Ferry and colleagues also analyzed survival by performance status (PS), a strong prognostic predictor of OS and PFS.

They calculated the following median PFS data: 1.8 months for PS0; 1.4 months for PS1; and 1 month for PS2.

They calculated the following median OS data: 6 months for PS0; 3.9 months for PS1; and 1.97 months for PS2.

“Performance status is a strong predictor of OS,” Ferry said in a press release. “For patients with PS2, the median survival of 1.97 months was much worse than those with PS1 or PS0. Future studies should probably concentrate on PS0 or PS1 patients.”

Gefitinib treatment also improved dysphagia and odynophagia (P=.004), according to study results.

For more information:

Ferry DR. Abstract #20 LBA_PR. Presented at: European Society for Medical Oncology; Sept. 28-Oct. 2, 2012; Vienna.

Disclosure: The researchers report no relevant financial disclosures.

Perspective

Jean-Yves Douillard, MD, PhD

This study is interesting and innovative. As stated by the author, there is no standard of care for such disease in second-line [therapy]. However, more patients nowadays are eligible for second-line chemotherapy. The COG study showed that gefitinib at the high dose of 500 mg per day improves PFS, the primary endpoint, with a significant reduction of 21% in the risk of progression, but a modest benefit of the median (2 weeks). The improved PFS may reflect a benefit in a subgroup of patients sensitive to gefitinib. The ancillary study TRANSCOG is looking at a predictive biomarker, possibly an EGFR mutation as seen in lung cancer. Hopefully, a biomarker predicting efficacy will be identified to allow the use of gefitinib in esogastric cancer in a personalized fashion. Considering the present practice, however, future studies should have a more active treatment choice than placebo in the control arm.

Jean-Yves Douillard, MD, PhD

Professor of medical oncology

University of Nantes, France

Disclosures: Douillard reports no relevant financial disclosures.

European Society for Medical Oncology Congress

Gefitinib extended PFS in esophageal cancer

Perspective