Second-line docetaxel in patients with relapsed oesophagogastric adenocarcinoma
Results of Cougar-02, randomised phase III study of docetaxel versus active symptom control
- Date : 05 Feb 2013
- Topic : Gastrointestinal cancers
A phase III study presented as a late breaking abstract at the tenth annual Gastrointestinal Cancers Symposium (24-26 January, 2013) in San Francisco, showed that second-line treatment with docetaxel results in longer overall survival compared with active symptom control in patients with advanced oesophagogastric cancer whose disease progressed despite first-line chemotherapy. While this strategy is already widely used, this UK study provides more evidence of survival benefit from second-line therapy with docetaxel.
Adenocarcinoma is the most common form of oesophagogastric cancer and the incidence of oesophageal adenocarcinoma is on the rise. Patients with oesophagogastric adenocarcinoma have poor outcomes with currently available therapies. All patients who present with advanced disease at diagnosis, and most (60-70%) who present with local disease, relapse after first-line chemotherapy. Without second-line therapy, the median survival time is 3 months. Randomised trials have recently suggested a small survival benefit for second-line chemotherapy with taxanes or irinotecan. There is very little data on quality of life or survival, particularly in patients who progress shortly after first-line therapy.
According to Dr Hugo Ford, lead author of the study and director of cancer services at Addenbrooke’s Hospital in Cambridge, UK, the current practice in the United States and many European countries is to give second-line chemotherapy to patients with oesophagogastric cancers, even though the level of evidence isn’t high. According to Dr Ford, this is the first trial to show second-line chemotherapy extends survival, without causing deterioration in quality of life.
COUGAR-02 was a multicenter open-label, randomised controlled phase III trial for patients with locally advanced or metastatic oesophagogastric cancer, performance status (PS) 0-2, who had progressed within 6 months of previous platinum/fluoropyrimidine chemotherapy. Patients were randomised (1:1) to receive either docetaxel for up to 6 cycles or active symptom control, which could include any treatment thought by the treating clinician to be appropriate for the management of symptoms including radiotherapy, steroids and supportive medications. The primary endpoint was overall survival. Secondary endpoints were response rate, toxicity, health related quality of life and healthcare resource use.
In this UK-based study, 168 patients were randomly assigned to wither docetaxel or active symptom control. Median age was 65 years (range 28-84), 81% were male. Performance status at randomisation was 0 for 27%, 1 for 57% and 2 for 15%. Site of disease was stomach in 46%, oesophagogastric junction in 34% and oesophagus in 20%; 86% had metastatic disease. From randomised patients, 43% progressed during previous chemotherapy, 28% progressed within 3 months of end of previous chemotherapy and 29% progressed between 3 and 6 months. Nineteen (23%) patients completed 6 chemotherapy cycles (median 3 cycles per patient). The main reasons for not completing treatment were progression and toxicity.
The median overall survival among patients who received docetaxel was 5.2 months, roughly 50% longer than the 3.6 months among those who received active symptom control (HR=0.67 (95% CI 0.49-0.92); p=0.01). The survival benefit was evident across the different tumour sites and stages of cancer and did not differ by patient age or gender. The greatest benefit was observed in patients with PS 0. After chemotherapy 7% had a partial response and 46% stable disease. Grade 4 toxicity was reported for 21% on docetaxel. Preliminary analysis of overall and disease-specific quality of life suggests that patients receiving second-line therapy with docetaxel have improved pain scores and no loss in global quality of life.
Besides docetaxel, patients with oesophagogastric cancers may receive irinotecan and paclitaxel as second-line therapy. The study authors concluded that addition of docetaxel to active symptom control significantly improved overall survival, and docetaxel can be considered a standard of care in this setting.
All study investigators disclosed relations with Sanofi: Dr Hugo Ford - Research Funding from Sanofi; Dr Gary William Middleton - Consultant or Advisory Role with Sanofi; Dr Ian Chau - Consultant or Advisory Role with Sanofi, Honoraria from Sanofi; Dr David Cunningham - Research Funding from Sanofi.
The 2013 Gastrointestinal Cancers Symposium was co-sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Surgical Oncology (SSO).
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