ESMO World GI 2015: SENRI Trial Evaluates NK1 Antagonists for Emesis Prevention in Oxaliplatin-Based Chemotherapy
The SENRI trial has opened the window to evaluate neurokinin 1 (NK1) antagonists for emesis prevention in patients taking oxaliplatin chemotherapy, said European Society for Medical Oncology World Congress on Gastrointestinal Cancer (ESMO) spokesperson and antiemetics expert Fausto Roila, MD. The results of these evaluations were presented July 1 at ESMO (Abstract O-0001) in Barcelona, Spain.
Dr. Roila commented, “Until now, we have said that NK1 antagonists have no role in the prevention of emesis in oxaliplatin chemotherapy, classified as having a moderate emetogenic risk only.”
Study Findings
The multicenter, open-label, randomized phase III SENRI trial evaluated the NK1 antagonist aprepitant for the prevention of nausea and vomiting induced by oxaliplatin-based chemotherapy in Japanese patients with colorectal cancer. Patients were randomized in a 1:1 ratio to the control group (5-HT3 receptor antagonist plus dexamethasone) or aprepitant group (5-HT3 receptor antagonist plus dexamethasone plus aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant in the second course. The primary endpoint was the rate of patients with no emesis. The results presented also included an analysis of the potential effect of gender on treatment response.
The trial enrolled 413 patients from 25 centers in Japan. Significantly more patients in the aprepitant group achieved no vomiting in the delayed phase and overall than those in the control group. Rates of overall complete response were lower in women than in men in both the control and aprepitant groups. In women, the rates of no nausea and complete protection were significantly higher in the aprepitant group than in the control group.
“We found that the three-drug combination antiemetic therapy of aprepitant, a 5-HT3 receptor antagonist, and dexamethasone significantly increased the inhibition rate of vomiting and nausea,” said lead study author Junichi Nishimura, MD, Assistant Professor at Osaka University in Japan. “The inhibition rate was especially clear in females. This three-drug combination might be a good antiemetic treatment option for oxaliplatin-based chemotherapy in patients with colorectal cancer.”
Further Research Needed
Standard prophylaxis for the prevention of acute emesis is a 5-HT3 receptor antagonist plus dexamethasone and for delayed emesis is corticosteroids. The only previous randomized trial evaluating the addition of an NK1 antagonist to prevent oxaliplatin- induced emesis found no benefit.
“Unfortunately, the two studies produced different results,” said Dr. Roila. “My opinion is that, because we have contrasting results, we need to await new data from other studies before we can conclude whether or not NK1 antagonists can be added to a 5-HT3 receptor antagonist plus dexamethasone in patients treated with oxaliplatin-based chemotherapy.”
Commenting on the new gender analysis, Dr. Roila said: “Women generally experience more chemotherapy-induced emesis than men. The addition of aprepitant induced an increase of overall complete response both in males and in females, from 64% to 78% in females and from 81% to 90% in males.”
He concluded, “The findings of the SENRI trial have important implications because they raise the possibility that NK1 antagonists may prevent emesis in patients treated with oxaliplatin-based chemotherapy. Oxaliplatin is a widely used antineoplastic drug, both as adjuvant treatment for colorectal cancer and for the metastatic diseases of many cancers of the gastrointestinal tract, the pancreas, and the biliary tract.”
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