Rolapitant Reduced Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy or Anthracycline/Cyclophosphamide
In a phase III study reported in The Lancet Oncology, Schwartzberg et al found that the addition of rolapitant to serotonin (5-HT3) receptor antagonist and dexamethasone treatment significantly improved complete response rates in prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens.
Study Details
In this double-blind trial, patients from 170 sites in 23 countries were randomly assigned between March 2012 and September 2013 to receive oral rolapitant 180 mg or placebo 1 to 2 hours before the administration of moderately emetogenic chemotherapy. All patients received oral granisetron 2 mg and oral dexamethasone 20 mg on day 1 (except for those receiving taxanes, who received dexamethasone according to the package insert) and granisetron 2 mg on days 2 and 3. Treatment was given for up to six cycles, with a minimum of 14 days.
A total of 666 patients in each group received at least one dose of study drug and were included in the modified intention-to-treat population. Among them, anthracycline/cyclophosphamide regimens were received by 344 patients in the rolapitant group and 359 patients in the control group. The primary endpoint was the proportion of patients achieving a complete response, defined as no emesis or use of rescue medication in the delayed phase (> 24–120 hours) after initiation of chemotherapy in cycle 1.
Delayed Phase Outcomes
Complete response during the delayed phase was observed in 71% of the rolapitant group vs 62% of the control group (odds ratio [OR] = 1.6, P = .0002), including 67% vs 60% among patients receiving anthracycline-cyclophosphamide regimens (OR = 1.4, P = .04) and 76% vs 64% among those receiving other moderately emetogenic regimens (OR = 1.8, P = .0008).
Acute and Overall Phases Outcomes
Among all patients, complete response during the acute phase (0–24 hours) was achieved in 83% vs 80% (P = .1425), including 77% vs 77% among patients receiving anthracycline-cyclophosphamide regimens (P = .9659) and 91% vs 84% among those receiving other regimens (P = .0163).
During the overall phase (0–124 hours), complete response was achieved in 69% vs 58% (P < .0001), including 63% vs 55% among patients receiving anthracycline-cyclophosphamide regimens (P = .0332) and 75% vs 61% among those receiving other regimens (P = .0003).
Adverse Events
The incidence of adverse events during cycle 1 was similar in the rolapitant and control groups, with the most frequently reported treatment-related adverse events being fatigue (3% vs 2%) and constipation (3% vs 3%). Adverse events led to discontinuation of treatment in 2% vs 2%. The most common grade 3 or 4 adverse event in the rolapitant group was neutropenia (5% vs 3%). No serious adverse events were considered treatment-related.
The investigators concluded: “Rolapitant in combination with a 5-HT3 receptor antagonist and dexamethasone is well tolerated and shows superiority over active control for the prevention of chemotherapy-induced nausea and vomiting during the 5-day (0–120 h) at-risk period after administration of moderately emetogenic chemotherapy or regimens containing an anthracycline and cyclophosphamide.”
Lee S. Schwartzberg, MD, of The West Clinic, Memphis, is the corresponding author of The Lancet Oncology article.
The study was funded by Tesaro, Inc. For full disclosures of the study authors, visit www.thelancet.com/journals/lanonc.
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