Second-line gefitinib doesn't improve esophageal cancer survival

By Reuters Staff

NEW YORK (Reuters Health) - Gefitinib does not improve overall survival in patients with esophageal cancer that progresses after chemotherapy, but it does produce a significant improvement in odynophagia, researchers report.

"The use of gefitinib as a second-line treatment in esophageal cancer . . . has palliative benefits in a subgroup of these difficult-to-treat patients with short life expectancy," Dr. Susan Dutton of the University of Oxford in the UK and colleagues wrote in a paper online June 18 in Lancet Oncology.

"Future research should focus on identification of predictive biomarkers to identify this subgroup of benefiting patients," they said.

They note that use of second-line chemotherapy in esophageal cancer patients with progressive disease is "controversial with only scarce data for clinical effectiveness."

While some clinicians may extrapolate data from studies of second-line therapy in gastric cancer, they add, "in view of the clinical and biological differences between gastric and esophageal cancer, this approach is likely to result in suboptimum treatment for patients with esophageal cancer."

Given that most esophageal cancers express EGFR, and this marker is linked to worse survival, Dr. Dutton and her team designed a phase III study of the EGFR tyrosine kinase inhibitor gefitinib in previously treated esophageal cancer patients with advanced disease, recruiting 450 patients from 48 UK centers. One patient withdrew consent, leaving 224 patients randomized to 500 mg gefitinib per day and 225 to placebo.

There was no difference between the two groups in the primary endpoint of overall survival, which was a median 3.73 months for the gefitinib group and 3.67 months for the placebo group. There was a marginal difference in progression-free survival, which was a median 1.57 months for the gefitinib group and 1.17 months for placebo patients (p=0.02).

One prespecified patient-reported outcome, odynophagia, did show significant improvement in the patients on gefitinib. Adverse events in the gefitinib group included diarrhea, in 16% of patients; skin toxicity, in 21%; and fatigue, in 11%. Most adverse events were grade 2.

"Without biomarker stratification, gefitinib has marginal clinical benefits in advanced esophageal cancer, however, patient-reported outcomes suggest some useful palliation of specific symptoms," Dr. Dutton and her team write. "Identification of a predictive biomarker to identify any gefitinib-responsive subgroup of patients with esophageal cancer would greatly increase clinical usefulness and is the priority for ongoing work."

The current study is the largest trial of second-line therapy in esophageal cancer, and is also the first to include a large number of patients with squamous-cell cancer, Dr. Hugo Ford of Addenbrooke's Hospital, Cambridge, UK writes in an editorial accompanying the study. Most patients in the study had adenocarcinoma, while 106 had squamous cell carcinoma.

While second-line chemotherapy has been shown to be helpful in patients with adenocarcinoma of the esophagus, Dr. Ford adds, "evidence for second-line therapy in squamous cancer is sparse."

"The results of this trial do not make a convincing case for the use of gefitinib, unless the results of the TRANSCOG study identify a potential biomarker," Dr. Ford added. "For patients with squamous-cell cancer progressing after first-line chemotherapy, supportive care is still a very real option, particularly for less fit patients and, despite the results from this high-quality trial, placebo or supportive care remains an appropriate control group for future clinical studies."

The authors did not respond to a request for comment by deadline.

SOURCE: http://bit.ly/1veRUQU

Lancet Oncol 2014.

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