Adding Aprepitant Improves Control of Oxaliplatin-Related Nausea, Vomiting in CRC

Fausto Roila, MD

Adding an NK1 antagonist (aprepitant or fosaprepitant) to a 5-HT3 receptor antagonist with dexamethasone improved antiemetic control for patients with colorectal cancer (CRC) treated with an oxaliplatin-based regimen compared with the 5-HT3 antagonist and dexamethasone alone, according to findings from the phase III SENRI trial.

The improvement in chemotherapy-induced nausea and vomiting (CINV) was particularly evident in female patients with CRC who were treated with the combination, according to Junichi Nishimura, MD, PhD, who presented findings at the 2015 World Congress on GI Cancer.¹ In the study, a complete response (CR), defined as no emetic episodes and no rescue therapy, was achieved in 78% of women in the NK-1 antagonist group compared with 64% in the control arm.

“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,” Nishimura, assistant professor at Osaka University in Japan, said in a statement. “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.”

The open-label phase III SENRI trial enrolled 413 Japanese patients with CRC who were treated with an oxaliplatin-based regimen. During the first cycle, patients were randomized to receive a 5-HT3 receptor antagonist plus dexamethasone with or without an NK1 antagonist. Aprepitant was administered at 125 mg on day 1 followed by 80 mg on day 2 and 3. Fosaprepitant was administered at 150 mg on day 1. In the second cycle of therapy, all patients were treated with either aprepitant or fosaprepitant.

Patients in the aprepitant/fosaprepitant group experienced significant improvements in CINV compared with the control arm. In the overall trial, vomiting was prevented in 95.7% of patients in the triplet arm compared with 83.6% with the standard doublet. Delayed emesis (day 7 or later) was prevented in 95.7% versus 84.7%, in the triplet and doublet arms, respectively.

“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," Fausto Roila, MD, director of the Medical Oncology Division at Santa Maria Hospital, Terni, Italy, said in a statement. "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.”

In addition to the promising findings for female patients presented at the World GI meeting, improvements in CINV were also characterized for men. In male patients, the CR rate with the NK1 antagonist was 90% versus 81% in the control arm.

“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," Roila said. “Until now we said that NK1 antagonists have no role in the prevention of emesis in oxaliplatin chemotherapy, classified as having a moderate emetogenic risk only.”

Prior to the SENRI study, other clinical trials showed a lack of benefit with the addition of the NK1 antagonist to standard anti-emetic treatment for oxaliplatin-treated patients. In a phase III study, the addition of the NK1 antagonist casopitant to ondansetron and dexamethasone failed to show an improvement in CINV rates.²

In this study, a single-dose of 90-mg casopitant in combination with the 5-HT3 receptor antagonist ondansetron and dexamethasone demonstrated a CR rate of 85% compared with 86% without casopitant (P = .7273). This lack of added benefit was seen in the overall, acute, and delayed phase.

“Unfortunately the two studies gave different results,” said 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.”

1. Nishimura J, Satoh T, Fukunaga M, et al, et al. A phase III trial of aprepitant in colorectal cancer patients receiving oxaliplatin-based chemotherapy (SENRI Trial). Ann Oncol. 2015;26 (suppl 4; O-001).
2. Hesketh PJ, Wright O, Rosati G, et al. Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study. Support Care Cancer. 2012;20(7):1471-1478.

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