SAN FRANCISCO—Second-line docetaxel improves both survival and quality of life in patients with esophageal or gastric cancers that have progressed after first-line chemotherapy, compared with symptom control, researchers reported during a news conference for the Gastrointestinal Cancers Symposium (Abstract LBA-4).
Oncologists commonly offer second-line chemotherapy to patients with advanced, relapsed esophageal or gastric cancer, based on data from studies suggesting that docetaxel or irinotecan might prolong survival. Until now, however, few data have been available regarding the treatment's impact on quality of life.
“This is the first trial to show quality-of-life benefit,” said first author Hugo Ford, MD, Director of Cancer Services at Addenbrooke's Hospital in Cambridge, UK. “Because of the short survival time, this is a very important finding in terms of informing patients about the likely benefit of the treatment that we're offering them.”
Between April 2008 and April 2012, a total of 168 patients enrolled in the Phase III study conducted at several centers in the UK. Patients had to have locally advanced or metastatic disease and have had disease progression within six months of their initial chemotherapy. Patients were randomly assigned to receive either docetaxel (at 75 mg/m2 every three weeks for up to six cycles) or active symptom control. Symptom control was up to the treating physician's discretion and could include anything except chemotherapy.
Patients in the docetaxel arm had a median overall survival of 5.2 months compared with 3.6 months for patients in the supportive care arm, which was a statistically significant difference.
Moreover, Ford said, patients in the docetaxel arm had better symptom scores than those in the supportive care arm, as assessed by the EORTC-30 quality-of-life questionnaire. The difference in symptom scores was primarily due to decreases in pain with chemotherapy, he said. There were no differences between the two groups in terms of functional and global quality-of-life scores, indicating that chemotherapy was not having adverse effects on patients' lives.
“We expected to see that the very fit patients would do better [with chemotherapy], and that was in fact the case,” The patients who seemed to get the most benefit were those who were very fit and had the longest interval between their last chemotherapy and their relapse or progression. But we did, in fact, see benefits across all the groups we studied, and no particular cohort did not seem to benefit from the chemotherapy given.”
Based on these data, the researchers conclude that docetaxel should be standard second-line therapy for these patients, as well as the standard against which future treatments should be compared.
Difficult Trial to Perform
Trials that compare active treatment with supportive care are very difficult to perform, according to the moderator of the news conference, Neal J. Meropol, MD, Chief of the Division of Hematology and Oncology at University Hospitals Case Medical Center and Case Western Reserve University School of Medicine. “But there are questions in oncology for which a supportive care arm is appropriate, including concern for worsening quality of life.
“The study presented is really a model, and is a critical type of study for providing an evidence base to guide our treatment decisions at points in time when our goals are palliative and not curative, and when we are talking about modest prolongations in survival.”
When asked about the relatively high proportion of patients in the chemotherapy arm (approximately 30%) who received only one or no cycles of chemotherapy, Ford said that fact just points to how aggressive the disease is. “What that tells you is that in an aggressive disease there are a significant number of people who don't benefit from chemotherapy and their prognosis is really very poor—in this disease, often just a matter of weeks. In a way, for me, it makes the case for those people who are benefiting from chemotherapy, that the benefits are even more marked than what we saw in the trial.”
His team has collected health care utilization data for patients enrolled in the study and will do cost-effectiveness studies in the future, which are important, he said.
“But the real question for me, is could we identify the patients who do really badly—the 30 percent who have only one cycle of chemotherapy—and either give them something different that they might do better with or no treatment at all.”
In the past researchers have thought that poor performance status might be useful for identifying these patients, but the results from the current trial do not bear that out. “We need more sophisticated ways to identify them so patients can get the best possible quality of life,” he said.
The trial was supported by Cancer Research UK, and the drug was provided free of charge by Sanofi-Aventis.
The multidisciplinary symposium is co-sponsored by the American Gastroenterological Association Institute, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.