A phase III study from the United Kingdom has shown that second-line treatment with docetaxel improves overall survival of patients with advanced esophagogastric cancer.¹ The strategy has already been widely adopted, but COUGAR-02 is the first study to provide definitive evidence of a survival benefit with docetaxel given in the second-line setting, said Hugo Ford, MD, of Addenbrooke’s Hospital in Cambridge, United Kingdom, at the 2013 Gastrointestinal Cancers Symposium in San Francisco.

Patients with advanced disease who relapse after first-line chemotherapy have a median overall survival of only 3 months. Recent studies have suggested that second-line treatment may extend survival.

“The current practice in the United States and much of Europe is to give second-line chemotherapy, even though the evidence isn’t as strong as we would like and there has been a lack of robust quality-of-life data,” he said. “This is the first definitive trial of second-line chemotherapy in a Western population, and it was adequately powered to include robust quality-of-life assessments. In this well-defined and homogeneous poor-prognostic group, docetaxel provided a significant overall survival benefit over active symptom control, with improvements in pain scores and no loss in global quality of life.”

According to Dr. Ford, the study confirms docetaxel as a standard second-line therapy after failure of platinum/fluoropyrimidine in selected patients with advanced esophagogastric cancer.

Study Details

COUGAR-02 enrolled 168 patients with locally advanced or metastatic esophagogastric adenocarcinoma with disease progression within 6 months of first-line treatment.  Patients were randomized to docetaxel (75 mg/m² every 3 weeks for up to six cycles) or active symptom control, which included radiotherapy, steroids, and/or supportive care. Partial responses to chemotherapy were observed in 7%, and disease was stabilized in 46%.

Treatment with docetaxel significantly reduced mortality by 33%, improving median overall survival from 3.6 months in the control arm to 5.2 months in the docetaxel arm (P = .01), Dr. Ford reported.

“Adjusting for prognostic factors, the treatment effect remained significant,” he said. This was most marked in those patients with longer disease-free interval, but a consistent trend for improved survival with docetaxel was seen in patients with progression on or within 3 months of treatment. Among the subgroups, benefit was also notable for “very fit” patients with ECOG performance status of 0.

Docetaxel was associated with grade 4 toxicity in 21% of patients. Patients received a median of three cycles, and only 23% completed the full 18 weeks of treatment; most discontinuations were due to progressive disease (40%) and toxicity or symptoms (31%). For 28% of patients allocated to docetaxel, only zero or one cycle was possible, “which confirms the aggressive nature of this disease in some,” he said.

Quality of Life

Preliminary assessments showed that “global quality-of-life scores and the functional quality-of-life scores were not affected by chemotherapy. In other words, the chemotherapy did not have an adverse effect on how people functioned,” Dr. Ford said.

“The symptom scores were substantially better in the docetaxel arm, the most prominent of those being pain, which was markedly improved in the patients who received chemotherapy (P = .0008),” he added.

Benefits were seen across all groups, with no cohort of patients seeming to fare worse with chemotherapy, he added.

Neal J. Meropol, MD, Professor and Chief of Hematology/Oncology at University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, who moderated a press briefing, commented that the COUGAR-02 study is “a model for providing an evidence base to help guide our treatment decisions at points in time when the goals are palliative and not curative, and a model for the type of study we would like to see more of. Treatment toward the end of life is an area where we have fallen a little short (regarding evidence) and we need to pay additional attention.” ■

Disclosure: Dr. Ford has received research funding from Sanofi. Dr. Meropol reported no potential conflicts of interest.

Reference

1. Ford H, Marshall A, Wadsley J, et al: COUGAR-02: A randomized phase III study of docetaxel versus active symptom control in patients with relapsed esophagogastric adenocarcinoma. 2013 Gastrointestinal Cancers Symposium. Abstract LBA4. Presented January 24, 2013.