Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials

Rapoport, Bernardo; Chasen, Martin; Gridelli, Cesare; Urbán, László; Modiano, Manuel; Schnadig, Ian D.; Poma, Allen; Arora, Siddharth; Kansra, Vikram; Schwartzberg, Lee S.; Navari, Rudolph M.

doi:10.1016/s1470-2045(15)00035-2

Cited by 128 publications

(177 citation statements)

References 19 publications

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“…Rolapitant was well tolerated in the carboplatin subgroup, and this was consistent with the safety profile reported in phase 3 studies 12, 13. The incidence of adverse events with rolapitant was comparable to the incidence with the control, and these adverse events were generally considered to be related to chemotherapy or the underlying disease.…”

Section: Discussionsupporting

confidence: 80%

Efficacy of the neurokinin‐1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin‐based chemotherapy

Hesketh

Schnadig

Schwartzberg

et al. 2016

Cancer

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BACKGROUNDRolapitant, a novel neurokinin‐1 receptor antagonist, provided effective protection against chemotherapy‐induced nausea and vomiting (CINV) in a randomized, double‐blind phase 3 trial of patients receiving moderately emetogenic chemotherapy or an anthracycline and cyclophosphamide regimen. The current analysis explored the efficacy and safety of rolapitant in preventing CINV in a subgroup of patients receiving carboplatin.METHODSPatients were randomized 1:1 to receive oral rolapitant (180 mg) or a placebo 1 to 2 hours before chemotherapy administration; all patients received oral granisetron (2 mg) on days 1 to 3 and oral dexamethasone (20 mg) on day 1. A post hoc analysis examined the subgroup of patients receiving carboplatin in cycle 1. The efficacy endpoints were as follows: complete response (CR), no emesis, no nausea, no significant nausea, complete protection, time to first emesis or use of rescue medication, and no impact on daily life.RESULTSIn the subgroup administered carboplatin‐based chemotherapy (n = 401), a significantly higher proportion of patients in the rolapitant group versus the control group achieved a CR in the overall phase (0‐120 hours; 80.2% vs 64.6%; P < .001) and in the delayed phase (>24‐120 hours; 82.3% vs 65.6%; P < .001) after chemotherapy administration. Superior responses were also observed by the measures of no emesis, no nausea, and complete protection in the overall and delayed phases and by the time to first emesis or use of rescue medication. The incidence of treatment‐emergent adverse events was similar for the rolapitant and control groups.CONCLUSIONSRolapitant provided superior CINV protection to patients receiving carboplatin‐based chemotherapy in comparison with the control. These results support rolapitant use as part of the antiemetic regimen in carboplatin‐treated patients. Cancer 2016;122:2418–2425. © 2016 American Cancer Society.

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Section: Discussionsupporting

confidence: 80%

Efficacy of the neurokinin‐1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin‐based chemotherapy

Hesketh

Schnadig

Schwartzberg

et al. 2016

Cancer

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“…The statistically significant 8.0% absolute treatment difference in CR (equating to a 14.2% relative difference) demonstrated by APF530 versus the standard of care intravenous 5-HT 3 RA is similar in magnitude to treatment differences demonstrated in other trials where an NK-1 RA was added to the traditional two-drug regimen, leading to changes in guidelines and standard practice [26,28,30,33]. MAGIC is the first Phase III efficacy trial to demonstrate superiority of a 5-HT 3 RA over another in preventing CINV following HEC in the presence of an NK-1 RA.…”

Section: Proportion Of Patients With Nausea (%)supporting

confidence: 52%

“…However, previous pivotal Phase III efficacy studies were of two-drug versus two-drug, or three-drug versus two-drug regimens [9,10,19,20,[26][27][28][29]. Other registrational HEC trials evaluating antiemetics as part of a three-drug regimen (i.e., aprepitant, NEPA, rolapitant) involved two-drug regimen comparator arms only (5-HT 3 RA and dexamethasone) [26,30]. The MAGIC Trial represents the Schnadig, Agajanian, Dakhil et al future science group first pivotal Phase III efficacy trial in HEC using a consensus guideline-recommended three-drug regimen in both arms.…”

Section: Discussionmentioning

confidence: 99%

APF530 (Granisetron Injection Extended-Release) in a Three-Drug Regimen for Delayed CINV in Highly Emetogenic Chemotherapy

et al. 2016

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“…In a phase 2 trial, rolapitant produced significantly better complete responses in CINV versus a regimen of ondansetron plus dexamethasone (35). In three phase 3 investigations, this agent elicited higher responses particularly in the delayed phase of CINV than control groups who received a 5-HT 3 antagonist and corticosteroid (36). A recent pooled analysis of these controlled trials reported a relative risk for complete response of 1.23 (95% CI; 1.18–1.33, P<0.00001) versus comparator regimens with relative risks of no nausea of 1.17 (95% C, 1.04– 1.32, P=0.008) and no vomiting of 1.24 (95% CI; 1.18–1.31, P<0.00001)(37).…”

Section: Medications Used To Treat Nausea and Vomitingmentioning

confidence: 99%

“…Rolapitant has the additional benefit of not inducing or inhibiting with the CYP3A4 pathway, permitting safer use of other medications metabolized by this pathway including corticosteroids and 5-HT 3 antagonists (40). The most prevalent side effects with rolapitant include constipation, headache, dyspepsia, and hiccups (36). …”

Section: Medications Used To Treat Nausea and Vomitingmentioning

confidence: 99%

Newest Drugs for Chronic Unexplained Nausea and Vomiting

Hasler

2016

Curr Treat Options Gastro

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OPINION STATEMENT Chronic unexplained nausea and vomiting (CUNV) refers to a symptom complex defined by nausea and/or vomiting with normal diagnostic testing, including anatomic assessments (including upper endoscopy) and measures of upper gut function (e.g. gastric emptying testing). Nausea and vomiting in this condition are postulated to result from aberrant peripheral or central neurohumoral activity. A substantial subset of patients satisfies this diagnosis as more than half of individuals referred for scintigraphic testing exhibit normal gastric emptying rates. No randomized, placebo-controlled trials of any medication treatment have been performed in CUNV. However, agents with potential therapeutic benefit in CUNV include antiemetic drugs, neuromodulatory treatments which are proposed to act by reducing gastric sensitivity, and medications with prokinetic action to stimulate upper gut propulsion. Recently approved drugs with antiemetic capability include serotonin antagonists with novel modes of delivery and neurokinin antagonists with or without additional serotonergic blocking capabilities. Existing neuroleptics and pain modifying neuromodulatory therapies with fortuitous antiemetic benefits are being considered for their benefits in this disorder. Furthermore, current investigations will define potential therapeutic actions of agents that stimulate gastric emptying via action on gastroduodenal serotonin, motilin, and ghrelin receptors. This current research may broaden the treatment options for refractory cases of unexplained nausea and vomiting.

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Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials

Cited by 128 publications

References 19 publications

Efficacy of the neurokinin‐1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin‐based chemotherapy

Efficacy of the neurokinin‐1 receptor antagonist rolapitant in preventing nausea and vomiting in patients receiving carboplatin‐based chemotherapy

APF530 (Granisetron Injection Extended-Release) in a Three-Drug Regimen for Delayed CINV in Highly Emetogenic Chemotherapy

Newest Drugs for Chronic Unexplained Nausea and Vomiting

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