This article is more than 5 years old. Information may no longer be current.
Second-line docetaxel effective in refractory esophagogastric adenocarcinoma
Second-line docetaxel improved survival and was associated with similar quality-of-life outcomes compared with active symptom control in patients with platinum- and fluoropyrimidine-refractory esophagogastric adenocarcinoma, according to results of a phase 3 study.
The COUGAR-02 study included 168 patients enrolled at 30 centers in the United Kingdom between 2008 and 2012. All patients had advanced adenocarcinoma of the esophagus, esophagogastric junction or stomach. They all experienced disease progression within 6 months of platinum-fluoropyrimidine treatment and had an ECOG performance status between 0 and 2.
Researchers assigned half of the patients to 75 mg/m2 IV docetaxel every 3 weeks for up to six cycles plus active symptom control. The other half of patients received active symptom control alone.
Median follow-up was 12 months (interquartile range, 10-21).
During the study, 161 patients (96%) died. Eighty of these patients were assigned docetaxel, and 81 were in the active symptom control arm.
Median OS in the docetaxel arm was 5.2 months (95% CI, 4.1-5.9) compared with 3.6 months (95% CI, 3.3-4.4) in the active symptom control arm (HR=0.67; 95% CI, 0.49-0.92).
More patients assigned docetaxel experienced grade 3 or grade 4 neutropenia (15% vs. 0%), infection (19% vs. 3%) and febrile neutropenia (7% vs. 0%).
However, pain (P=.0008), nausea and vomiting (P=.02) and constipation (P=.02) were less common in the docetaxel arm.
Researchers found that global health-related quality of life was similar between the two arms (P=.53).
Docetaxel was associated with improved disease-specific health-related quality of life with regard to dysphagia (P=.02) and abdominal pain (P=.01).
“On the basis of our findings, we believe that chemotherapy should be offered to fit patients for the second-line treatment of esophagogastric adenocarcinoma, and that treatment with docetaxel can improve some aspects of quality of life for patients,” the researchers concluded.
Although these results might “end the debate” regarding second-line chemotherapy in this patient population, the results may be different in another setting, Se Hoon Park, MD, of the division of hematology-oncology at Sungkyunkwan University Samsung Medical Center in Seoul, Korea, wrote in an accompanying editorial.
“In the real world — outside of the strict enrolment criteria of a clinical trial — many patients develop peritoneal carcinomatosis during the course of their disease, leading to a rapid symptomatic deterioration and chemotherapy intolerance,” Park wrote. “Data from COUGAR-02 and other trials should be interpreted carefully because of the potential selection bias — only a small subset of patients continue to have a good performance status after first-line failure and are still physically fit enough to be offered second-line chemotherapy.”
Disclosure: The researchers report research funding/honoraria from and consultant roles with, Amgen, AstraZeneca, Celgene, Lilly Oncology, Merck Serono, Novartis and Sanofi.
Perspective
Back to TopFollowing initial disappointment with agents that target the vascular endothelial growth factor (VEGF) in the treatment of cancers of the esophagus and stomach, ramucirumab (IMC-1121B, Eli Lilly) — a monoclonal antibody targeting VEGFR2 — will have the potential to fill this treatment gap and also can be considered for patients who progressed on standard first-line therapy, according to the positive results of the REGARD trial, which compared ramucirumab with best supportive care (Fuchs CS. Lancet. 2013;doi:10.1016/S0140-6736(13)61719-5).
These interesting results are further corroborated by the recent release of the positive results from another randomized clinical trial, RAINBOW, which assessed the role of ramucirumab in combination with paclitaxel in second-line treatment compared with paclitaxel alone in patients with advanced esophagus and stomach adenocarcinoma. In the absence of a ramucirumab approval in this setting, and given its lower level of toxicity, weekly single-agent paclitaxel is the preferred option compared with the other two chemotherapy agents (docetaxel or irinotecan) with similar activity in this setting.
How about the case where ramucirumab gets its anticipated approval from the regulatory agencies for use in this disease setting? Weekly paclitaxel should be the favored choice again given its safe combinability with ramucirumab with further improvement in outcome.
Perspective
Back to TopWe often select treatments in this salvage setting based on extrapolation from first-line data, and frankly, because we want to be able to offer something that could be potentially helpful to our patients. Now, with the recently published COUGAR-02 study, we have firmer evidence that second-line chemotherapy (docetaxel) does indeed confer a statistically significant survival benefit compared with best supportive care, although one might argue whether the magnitude of benefit (a 1.6-month improvement in median survival) meets the completely arbitrary threshold of “clinically meaningful.”
Importantly, administration of docetaxel did not result in a diminution in patients’ global health-related quality of life. In fact, for certain disease-specific quality-of-life measures, it provided demonstrable benefit. This aspect was a valuable component to incorporate into the study design, as it helps inform our discussions with patients with regard to the goals and potential benefits of salvage treatment, including both quantitative and qualitative outcomes.
Between COUGAR-02 and the REGARD trial, which showed a survival benefit of the anti–VEGFR-2 monoclonal antibody ramucirumab (IMC-1121B, Eli Lilly) when given to a similar patient population, we now have two separate phase 3 studies that show clear evidence of antitumor activity, however modest, of two different therapies when administered in the second-line setting. This expanding array of options represents welcome news to those patients with advanced gastroesophageal cancer who are interested, and remain well enough, to continue with some form of systemic therapy.