ASCO Updates Antiemetic Guidelines to Include New Agent
The American Society of Clinical Oncology (ASCO) issued updated antiemetic guidelines recommending that patients who receive highly emetogenic chemotherapy regimens be offered a 3-drug combination of a neurokinin 1 (NK1) receptor antagonist, a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, and dexamethasone. The update was published November 2 in the online Journal of Clinical Oncology.
The evidence review leading to the update was prompted in part by the October 2014 US Food and Drug Administration approval of the NK1 receptor antagonist netupitant and the 5-HT3 receptor antagonist palonosetron to prevent acute and delayed nausea and vomiting in patients receiving initial and repeat courses of chemotherapy. Administered orally, the netupitant and palonosetron (NEPA) combination therapy consists of a fixed dose of 300 mg of netupitant combined with 0.50 mg of palonosetron.
Two phase III randomized trials and one phase II randomized trial formed the update’s evidence base. One of the phase III trials compared NEPA with palonosetron alone in 1449 patients receiving anthracycline plus cyclophosphamide chemotherapy. Dexamethasone was provided to all patients on the first day only. The study found that NEPA resulted in higher rates of complete response (no emesis or rescue medication) during both the acute and delayed phases than palonosetron, with similar safety profiles.
The second phase III trial evaluated NEPA over repeated cycles of highly or moderately emetogenic chemotherapy in patients who were chemotherapy-naïve. Patients were randomly assigned to receive NEPA or oral aprepitant plus oral palonosetron. Participants also received dexamethasone on a schedule based on chemotherapy emetogenicity. Three-quarters of the patients completed at least 4 cycles, and 40% completed 6 cycles. According to the study, the rates of complete response with NEPA were high across the various treatment cycles.
The phase II trial randomly assigned 694 chemotherapy-naïve patients scheduled to receive cisplatin-based chemotherapy to one of five different antiemetic treatment arms: netupitant at 100 mg, 200 mg, or 300 mg, each combined with oral palonosetron 0.50 mg; oral palonosetron 0.50 mg only; or 3-day aprepitant plus intravenous ondansetron 32 mg. Patients also received dexamethasone on days 1 through 4. According to study results, each netupitant–palonosetron dose produced higher complete response rates than palonosetron alone, although the 300 mg dose was most effective.
“Pending a full update of the 2011 guideline, this update provides expedited guidance regarding a new agent to prevent chemotherapy-induced nausea and vomiting,” wrote members of ASCO’s update committee. “Recommendations regarding other agents will be addressed in a subsequent, comprehensive guideline update.”
Hesketh PJ, Bohlke K, Lyman GH, et al. Antiemetics: American Society of Clinical Oncology focused guideline update [published online ahead of print November 2, 2015]. J Clin Oncol. doi:10.1200/JCO.2015.64.3635.