Washington, DC—For patients receiving highly emetogenic chemotherapy (HEC), optimal control of chemotherapy-induced nausea and vomiting (CINV) requires co-administration of antiemetics that inhibit multiple molecular pathways. At the 2017 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology Annual Meeting on Supportive Care in Cancer, our team from Sun Yat-sen University Cancer Center, Guangzhou, China, presented results from the first head-to-head clinical trial comparing neurokinin-1 receptor antagonist (NK1 RA) regimens. These findings demonstrated that a single oral dose of netupitant plus palonosetron (NEPA), the first fixed combination of the selective NK1 RA netupitant (300 mg) and the clinically and pharmacologically active 5-HT3 receptor antagonist palonosetron (0.5 mg), was noninferior to a 3-day oral combination regimen of aprepitant and granisetron (APR/GRAN) in preventing HEC-associated CINV.
Our phase 3, randomized, double-blind clinical trial was conducted in 828 chemotherapy-naïve patients receiving cisplatin-based HEC. Patients received a single dose of NEPA (N = 412) on day 1 or APR/GRAN (N = 416) on days 1 to 3. All patients received oral dexamethasone on days 1 to 4.
The primary efficacy end point was complete response, defined as no emesis or rescue medication during the overall (0-120 hours) phase of CINV, which comprises the acute (0-24 hours) and delayed (25-120 hours) phases. Noninferiority was defined as a lower 95% confidence interval (CI) greater than the noninferiority margin set at –10%.
Secondary end points included no emesis, no rescue medication, no significant nausea (defined as <25 mm on a 100-mm visual analog scale), and daily rates of CINV events (emesis and/or rescue medication use).
For the primary efficacy end point, 73.8% of patients receiving NEPA achieved a complete response during the overall phase compared with 72.4% in the APR/GRAN group, demonstrating the noninferiority of the NEPA regimen (95% CI, –4.5%-7.5%). In addition, daily CINV events declined numerically over time, with NEPA reaching significance at day 5 compared with the APR/GRAN arm, suggesting a benefit in preventing delayed CINV. Although the overall complete response rates were similar in the 2 study arms, the rates of patients experiencing daily CINV remained between 13% to 15% in the APR/GRAN arm, and declined from 16% to 8% over 5 days in the NEPA study arm (P = .0063). The NEPA safety profile was comparable to that of APR/GRAN.
The availability of an oral antiemetic agent targeting 2 antiemetic pathways in a convenient single capsule is a benefit for patients receiving HEC. When administered as a single oral dose only once per cycle, such an agent may help to overcome potential adherence hurdles, especially when CINV treatment guidelines recommend targeting 2 critical pathways. The rationale for NEPA is based on the fact that palonosetron prevents nausea and vomiting during the acute phase of CINV, and netupitant does so during the acute and delayed phases.
Oral NEPA has been approved in the United States and Europe for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including HEC. Its approval by the FDA was based on evidence of superior CINV prevention compared with palonosetron in cisplatin- and doxorubicin/cyclophosphamide–based chemotherapy settings.
NEPA is recommended by various antiemetic guidelines, including those issued by the National Comprehensive Cancer Network, for HEC and moderately emetogenic chemotherapy (MEC); the American Society of Clinical Oncology, for HEC and MEC; and the Multinational Association of Supportive Care in Cancer together with the European Society for Medical Oncology, for HEC and MEC doxorubicin/cyclophosphamide– and carboplatin-based chemotherapy.
Increasing use of NEPA would potentially help greater numbers of patients avoid CINV, relieving them of one of the more debilitating complications of anticancer therapy.