Second-Line Docetaxel Affirmed for Esophagogastric Cancer

Zosia Chustecka

January 23, 2013

Results from a phase 3 study "affirm" the use of docetaxel as a second-line treatment for patients with advanced esophageal and gastric cancers who have progressed after first-line chemotherapy, according to researchers from the United Kingdom.

This strategy is already widely used in clinical practice, "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 study is "the first trial to show that second-line chemotherapy extends survival without causing deterioration in quality of life," he said.

Dr. Ford was speaking at a presscast organized by the American Society of Clinical Oncology, one of several professional societies supporting the 2013 Gastrointestinal Cancers Symposium, being held January 24 to 26 in San Francisco, California.

The study, known as COUGAR-02, involved 168 patients from 31 hospitals in the United Kingdom. Median age was 65 years, and the majority of patients (81%) were male. Most (86%) had metastatic disease, and the site of disease was the stomach in 46% of patients, the esophagogastric junction in 34%, and the esophagus in 20%. All patients had progressed within 6 months of initial chemotherapy.

Patients were randomized to receive second-line chemotherapy with docetaxel (75 mg/m² every 3 weeks for up to 6 cycles) or active symptom control (including radiotherapy, steroids, and/or supportive medications).

Median overall survival was significantly better with docetaxel than with active symptom control (5.2 vs 3.6 months; hazard ratio 0.67; P = .01).

Although quality-of-life questionnaires (from the European Organisation for Research and Therapy of Cancer) demonstrated no differences between the 2 groups on global and functioning scores, they did indicate an improvement in symptom scores, with patients on docetaxel reporting less pain.

"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.

Two previous trials have suggested a survival benefit: a German trial using irinotecan that was discontinued early; and an Asian study investigating irinotecan and paclitaxel. However, in the Asian study, the patients with gastric cancer were younger and fitter, he noted.

Irinotecan, paclitaxel, and docetaxel are already used in clinical practice in this setting, but the results of this study affirm docetaxel as a standard second-line therapy, Dr. Ford said.

Questions Over Offering Chemo

Neal Meropol, MD, chief of the division of hematology and oncology at the Case Western Reserve University in Cleveland, Ohio, who moderated the presscast, was asked to place this study in a wider context and to discuss how it fits with concerns about administering chemotherapy at the end of life. Such treatment has been questioned in recent years, particularly after a landmark study of patients with terminal lung cancer showed better survival with supportive care than with continued chemotherapy.

"First of all, not administering chemotherapy does not mean stopping treatment altogether," Dr. Meropol noted. Supportive care involves offering therapies that have a different goal, "but it is still treatment, and is still aggressive treatment," he explained.

"There is a lot of concern in the oncology community and beyond about how we approach the care of patients at the extremes, at the very end of life," Dr. Meropol acknowledged. "A lot of treatment is given to patients within weeks of their death, and because treatment is toxic, we are very cognizant of the question of whether patients are being harmed by this type of aggressive therapy."

Hence, the study by Dr. Ford and colleagues is "a model and a very critical study" that provides "an evidence base for guiding our treatment decisions," he said. "It's the type of study we would like to see more of," he added. one of the most clearly evidence-based fields of medicine. Dr. Neal Meropol

"Oncology as a field, in my view, is one of the most clearly evidence-based fields of medicine, in that most of what we do is based on high levels of evidence, but treatment toward the end of life is an area where we have fallen a little short," he said.

"I think that's exactly right," Dr. Ford added. "I think that there is a tendency, when people get toward the end of life, for desperation to become more important than sense," he said.

"This sort of study is difficult to perform, but it is extremely important" to gather these quality-of-life data, Dr. Ford added. His team also collected cost data from this study, which will be published at a later date, he said.

"The real question for me, from these data, is can we identify the group of patients who do really badly on chemotherapy" and offer this group some other treatment, he said.

About 30% of patients in this study received no docetaxel or only 1 cycle of it. "What that tells you is that in an aggressive disease, there are some patients who don't benefit from chemotherapy; they have a poor prognosis, measured in a matter of weeks," Dr. Ford said. At the moment, there is no way to identify these patients. This is an area where more work is needed, he explained.

However, this means that the effect in the patients who do benefit from chemotherapy is even more marked than it appears from the overall results, he added. The median number of docetaxel cycles administered was 3, and 19 patients (23%) completed the planned 6 cycles. The main reasons for stopping were disease progression and toxicity.

The main adverse effect from chemotherapy was myelosuppression, which is mostly asymptomatic but may be reflected in reports of lethargy, Dr. Ford noted. However, the quality-of-life data did not show any deterioration, so "we are quite comfortable that, overall, patient symptoms and quality of life were better with chemotherapy than without it."

The study was funded by Cancer Research UK, and docetaxel was supplied free of charge by sanofi-aventis. Dr. Ford and several coauthors report receiving research funding from Sanofi. Dr. Meropol reports acting as a consultant for Precision Therapeutics.

2013 Gastrointestinal Cancers Symposium (GICS): Abstract LBA4. To be presented January 24, 2013.