Preventing nausea and vomiting from the most emetogenic chemotherapy drugs is best accomplished with a three-drug combination, according to newly updated guidelines from the American Society of Clinical Oncology (ASCO).
The combination should include dexamethasone as well as a 5-hydroxytryptamine-3 (5-HT-3) receptor antagonist and a neurokinin-1 (NK-1) receptor antagonist, said Dr. Paul J. Hesketh and guideline coauthors.
An all-oral regimen that is a treatment option in this setting is the combination of netupitant and palonosetron – NEPA (Akynzeo) – together with dexamethasone, said Dr. Hesketh, an oncologist at Lahey Hospital and Medical Center, Burlington, Mass, and his coauthors.
For this interim update, the guideline committee used clinical trial data to “provide expedited guidance regarding a new agent,” pending a full update of ASCO’s antiemetic guideline (J Clin Oncol. 2015 Nov. 2. doi: 10.1200/JCO.2015.64.3635).
The fixed NEPA combination was approved in October of 2014 by the Food and Drug Administration for treatment of chemotherapy-induced nausea and vomiting (CINV). In clinical trials, NEPA plus dexamethasone was effective for both acute and delayed nausea and vomiting for the majority of individuals receiving moderately or highly emetogenic chemotherapy, and was more effective than just palonosetron combined with dexamethasone.
One phase III trial examined use of NEPA compared with palonosetron alone for individuals with cancer receiving the highly emetogenic combination of anthracycline plus cyclophosphamide. Overall, 74% of the NEPA group vs. 67% of the palonosetron group had a complete response, defined as no vomiting and no need for rescue medications (P less than .001). Another phase III trial found that NEPA’s effectiveness was durable over up to six courses of highly emetogenic chemotherapy, and that the drug was safe over time.
The approved fixed-dose combination of 300 mg of netupitant and 0.5 mg of palonosetron is meant to be taken as a one-capsule dose 1 hour before chemotherapy.
The mechanism of action of NK-1 antagonists, which block substance P from binding to neurokinin, can add a more durable anti-emetic effect and prevent or minimize late-onset CINV. A dose-ranging phase II clinical study of NEPA for CINV in treatment-naive patients receiving cisplatin for solid tumors found that the highest dose of netupitant tested, 300 mg, resulted in the least need for rescue medication, though all doses were significantly more effective in achieving complete response than palonosetron alone, or than ondansetron plus aprepitant.
A real-world consideration for patients and oncologists is that NEPA is an oral medication meant to be taken at home. This means that patients will have to fill – and pay for – NEPA prescriptions. “The out-of-pocket cost will vary by insurance plan, and this point should be discussed with patients,” said Dr. Hesketh and his coauthors.
Full cost analyses are underway; NEPA’s steep cost may be offset, at least in part, by the avoidance of any additional rescue medication for chemotherapy-induced nausea and vomiting.
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