Adding the chemotherapy docetaxel to active symptom control in advanced esophagogastric adenocarcinoma improves survival of patients. These are the results of the phase III COUGAR-02 trial.
Adding the chemotherapy docetaxel to active symptom control (ASC) in advanced esophagogastric adenocarcinoma improves survival of patients. These are the results of the phase III COUGAR-02 trial. Based on these results, presented at the American Society of Clinical Oncology (ASCO) 2013 Gastrointestinal Cancers Symposium, docetaxel should now be considered standard of care, according to the researchers.
The therapy approach is already widely used as treatment of advanced esophagogastric cancer. “Current practice in the US and a lot of Europe is to give second-line chemotherapy to patients with esophagogastric cancers, even though the evidence isn’t as strong as we would like,” said Hugo Ford, MD, director of cancer services at Addenbrooke’s Hospital in Cambridge, United Kingdom, the lead researcher who presented the study at the meeting. Ford added that for these cancer types, this is the first study to demonstrate a survival advantage after second-line therapy that does not result in a lower quality of life.
Overall survival of patients receiving ASC plus docetaxel survived 44% longer compared to those receiving ASC alone-a median 5.2 months compared to a median 3.6 months, respectively (P = .01, hazard ratio = 0.67). All patients had advanced esophageal and gastric cancers and had progressed after initial chemotherapy for their advanced cancer.
The COUGAR-02 was an open label, multicenter trial that enrolled 168 patients who had progressed within 6 months of receiving platinum and fluoropyrimidine chemotherapy. Patients were randomized one to one to receive either ASC or docetaxel 75 mg/m2 every 3 weeks for up to six cycles. ASC included physician’s choice of treatment to manage side effects and symptoms, including radiotherapy and steroids. Overall survival was the primary endpoint and health-related quality of life and toxicity were analyzed as secondary endpoints.
The median patient age was 65 and 81% of the patients in the trial were male. Forty-six percent of patients had cancer of the stomach, 20% had esophagus cancer, and 34% had cancer of the esophagogastric junction. Eighty-six percent of patients had metastatic disease. The survival benefit was seen for all three tumor types, for various stages of cancer, and in both genders.
Esophagogastric cancers account for about 39,000 new cases of cancer in the United States every year. Patients currently have poor outcomes. Those who are diagnosed with advanced forms of cancer relapse after initial treatment with chemotherapy. The median survival post–first-line therapy without aggressive second-line treatment is 3 months.
“Docetaxel is used first line in some patients in the US as part of the docetaxel, cisplatin, fluorouracil (DCF) regimen,” said Ford in an interview with Cancer Network. “However, in Europe and Asia it is generally used second line, though the evidence supporting its use is scanty, particularly as regards quality of life.”
Approximately one-fifth of patients taking docetaxel experienced grade 4 toxicity. Quality of life questionnaires showed that those patients given docetaxel had improved symptoms, improved pain relief, and no loss in overall quality of life compared to patients treated only with ASC.
“To me it was a good surprise that there was no deterioration in patients' function or global quality of life scores with chemotherapy, and that patients with performance status 2-those who are less fit-seemed to benefit as much as patients with only mild symptoms,” said Ford.
“This is important,” Dr. Ford said. These are the first quality-of-life data available for second-line chemotherapy in this setting, he emphasized. Because chemotherapy offers only a modest improvement in survival, it is important that it does not worsen quality of life for the time remaining, he explained.
The trial highlights that it is feasible and important to measure quality of life in clinical trials, particularly in patients in the last 3 months of life, said Ford. “Both physicians and patients have difficult decisions to make in these circumstances and there is often a tendency to cling to false hopes, or to concentrate purely on trying to extend life rather than to improve it.”
“This trial shows that in this situation chemotherapy with docetaxel can do both, albeit in a relatively modest way,” said Ford.
Another therapy has also shown positive results in the second line gastric cancer setting. The REGARD trial, also reported at ASCO GI shows ramucirumab extends survival by 6 weeks to 5.2 months for patients who have failed first-line platinum chemotherapy compared to best supportive care. Ramucirumab is a monoclonal antibody against VEGF receptor 2.