Second-line Docetaxel: Encouraging Survival, Quality-of-life Outcomes

British researchers presented data from the randomized, open-label phase 3 COUGAR-02 trial, where second-line docetaxel showed a significant 1.6-month (44%) improvement in median overall survival (OS) without degrading quality of life, compared to managed using active symptom control, in patients with relapsed esophagogastric adenocarcinoma. Patients treated with docetaxel received 75 mg/m2 every 3 weeks for up to six cycles.5  

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“Docetaxel can be considered a standard of care after failure of platinum or fluoropyrimidine therapy” for selected patients with advanced esophagogastric adenocarcinoma, reported Hugo Ford, MD, of Addenbrooke’s Hospital in Cambridge.

Preliminary analysis of quality-of-life data show that “patients receiving second-line therapy with docetaxel have improved pain scores and no loss in global quality of life,” Dr. Ford noted. Given the relatively short survival times for patients with relapsed esophagogastric adenocarcinomas, quality of life is an important consideration, he emphasized.

Neoadjuvant Therapies: ‘A Lot of Data, Little Clarity’

The evidence base remains more equivocal for what represents the best neoadjuvant therapy for surgically resectable esophageal tumors, noted Manisha Palta, MD, Christopher Willett, MD, and Brian Czito, MD, of the Department of Radiation Oncology at Duke University Medical Center in Durham, NC.

“There has been considerable debate in defining the optimal therapeutic approach to patients with resectable esophageal cancer,” they noted. “Some advocate a neoadjuvant chemotherapy alone approach, whereas others support neoadjuvant chemoradiotherapy. Although the results of phase 3 trials support either approach, there is little data directly comparing these neoadjuvant strategies.”6

For example, among studies of neoadjuvant chemotherapy regimens was a large, 802-patient trial by the Medical Research Council that found 5-year OS rates were better among patients with resectable esophageal cancer who had undergone two cycles of neoadjuvant 5-fluorouracil (5-FU) plus cisplatin (CDDP regimen; OS, 23%) compared with those who received surgery only (OS, 17%).6 Yet a similar study in which patients were administered three cycles of 5-FU plus cisplatin or surgery alone (n=443) found no OS advantage for neoadjuvant CDDP, Dr. Palta and colleagues noted.6

Similarly, they added, “(m)ultiple randomized trials have evaluated the role of CRT (chemoradiotherapy) in addition to surgery, also with conflicting results.” 6

No randomized phase 3 trial to date has enrolled enough patients for sufficient statistical power to detect survival differences between neoadjuvant CRT versus neoadjuvant chemotherapy alone. However, a 2011 meta-analysis of data representing more than 4,000 study participants, pooled from 24 randomized studies, suggests “an all-cause mortality benefit of 8.7% at 2 years” among patients receiving neoadjuvant CRT compared with those receiving only neoadjuvant chemotherapy.6,7

The available evidence “has demonstrated that neoadjuvant concurrent CRT improves local control and survival compared with surgery alone and offers a modest survival benefit compared to a neoadjuvant chemotherapy alone approach in patients with resectable esophageal cancer,” Dr. Palta’s team reported. “In the United States and many parts of Europe, CRT is the standard of care. Current and future research is aimed at identifying subsets of patients who will benefit from the addition of surgery to CRT, optimizing neoadjuvant and/or perioperative therapies, incorporating metabolic imaging to predict treatment responses and the incorporation of biologic agents to enhance treatment efficacy.”6

Research into molecular biomarkers “might also allow a more personalized treatment approach tailored to individual patients, ultimately making the debate of neoadjuvant chemotherapy or CRT moot,” they added.6