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LBA47
Phase 3 (P04832) trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in subjects receiving cisplatin-based chemotherapy:

Rolapitant reduces nausea and vomiting in phase III trial

Lugano/Madrid, 27 September 2014 – Rolapitant reduces nausea and vomiting in patients receiving cisplatin-based chemotherapy, according to the results of a phase III trial presented for the first time today at the ESMO 2014 Congress in Madrid, Spain.

Dr Martin Chasen, lead author and medical director, Palliative Care, Ottawa Hospital Cancer Centre, Canada, said: “This agent makes a significant difference in the way people tolerate their chemotherapy. Patients experienced no loss in quality of life and, in fact, many saw meaningful improvements. One of the patients in the rolapitant cohort reported that he had just finished 18 holes of golf one week after receiving chemotherapy. This is in sharp contrast to many patients on current standard anti-emetics that are too ill to get out of bed within a week after each cycle of cisplatin.”

“We must treat nausea and vomiting, not just the cancer,” added Chasen, emphasising that some patients are extremely sensitive to cisplatin effects and recalling that he had one or two patients with curable cancers who refused treatment after one round of cisplatin. “They preferred to die,” he said.

The phase III trial investigated rolapitant, a novel antagonist of the NK-1 receptor, for the prevention of severe nausea and vomiting often experienced by patients receiving cisplatin-based chemotherapy, which may cause dose reductions and treatment discontinuation. The multicentre trial randomised 532 patients 1:1 to receive rolapitant plus granisetron/dexamethasone or placebo plus granisetron/dexamethasone prior to cisplatin-based chemotherapy.

The primary endpoint was complete response (defined as the patient having no emesis and not requiring any rescue medication) in the delayed phase (>24-120 hours) post-chemotherapy. Key secondary endpoints included complete response during the acute (0-24 hours) and overall (0-120 hours) phases.

The trial met its primary endpoint, with 72.7% of patients receiving rolapitant achieving complete response in the delayed phase compared to 58.4% of those receiving placebo (p<0.001). Rolapitant also improved the complete response rate compared to placebo in the acute (83.7% vs 73.7%, p=0.005) and overall (70.1% vs 56.5%, p=0.001) phases. Patients receiving rolapitant tended to report that chemotherapy had less of an impact on their daily quality of life (72.8% vs 67.8%, p=0.231).

Chasen said: “Rolapitant demonstrated a significant effect in both the acute and delayed phases. Our primary endpoint was achieved in the delayed phase, an incredible result. We know that the NK-1 receptor in the brain must be blocked to control nausea and vomiting --there are other agents that block this for a short time; rolapitant is an exceptionally long term receptor blocker that binds to the receptor and remains in place for up to 120 hours, therefore not allowing the chemotherapy to induce nausea and vomiting.”

The investigators tested the agent in patients receiving cisplatin, possibly the strongest inducer of emesis.  “Without a doubt this drug can be evaluated in other less emetogenic cancer treatments,” said Chasen.

He pointed out that rolapitant may also save costs. For example, in Ottawa patients can have a visit from a nurse following their chemotherapy who administers intravascular hydration and nutrients. Chasen said: “Patients receiving rolapitant may not require this service. They are able to eat and drink as they should.”

-END-

Notes to Editors

LBA47_PR: Phase 3 (P04832) trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based chemotherapy.

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Information contained in this press release was provided by the abstracts authors and reflects the content of the studies. It does not necessarily express ESMO's point of view.

Session info

LBA47_PR                            Saturday, September 27, 2012 – 14:00 PM – 15:45 PM  - Pamplona

Abstract: LBA47_PR

Phase 3 (P04832) trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving cisplatin-based chemotherapy

M.R. Chasen¹, A. Poma², M.L. Hedley³, R. Martell², C. Gridelli^4
1Dept Palliative Rehabilitation, Elizabeth Bruyere HospitalDivision of Palliative Care, Ottawa, AB, CANADA, ²Medical, TESARO, Waltham, MA, USA, ³TESARO Inc., Waltham, MA, USA, ⁴Medical Oncology, UO Oncologia Medica"S.G. Moscati Hospital", Avellino, ITALY

Aim: Rolapitant is a highly selective competitive long acting NK-1 receptor antagonist that demonstrated safety and prevention of CINV in both phase 2 and 3 trials.

Methods: A multi-center, randomized double-blind phase 3 trial was conducted in patients (pts) receiving cisplatin-based chemotherapy. 532 pts were randomized 1:1 to receive oral rolapitant + granisetron/dexamethasone (G/D) or placebo + G/D prior to chemotherapy. The primary endpoint was complete response (CR; no emesis/no rescue meds) in the delayed phase (>24-120 hrs) post-chemotherapy. Key secondary endpoints included CR during acute (0-24 hrs) and overall (0-120 hrs) phases. Treatment comparisons were performed using a Mantel-Haenszel chi-square test; to control for type 1 error, testing was conducted in a stepwise fashion for key secondary endpoints. A regional CR analysis was prospectively conducted on North America (NA), Asia/South Africa (ASA), Europe (E), and Central/South America (CSA). Daily quality of life (QoL) was assessed via Functional Living Index-Emesis Questionnaire.

Results: Demographics were well balanced with a mdn age of 57.3y (range 20-90). The primary objective of this study was achieved with a higher CR rate in the delayed phase compared to placebo (72.7% vs 58.4%, p < 0.001). Statically significant results were also observed in key secondary endpoints of acute phase CR rate (83.7% vs 73.7%, p = 0.005), and overall CR rate (70.1% vs 56.5%, p =0.001). Slightly more pts reported no impact on daily QoL with rolapitant (72.8% vs 67.8%, p = 0.231). Addition of rolapitant conferred a CR improvement across geographic regions in both the delayed and acute phase. Treatment emergent AEs were consistent across both arms, and generally related to underlying medical condition or chemotherapy.

Conclusions: Rolapitant + G/D was well tolerated and superior to G/D alone in preventing CINV in pts receiving cisplatin-based therapies, and this effect was observed across geographic regions.

Disclosure: A. Poma, M.L. Hedley and R. Martell: is an employee of TESARO, the sponsor of this  abstract. All other authors have declared no conflicts of interest.

Keywords: highly emetogenic chemotherapy, rolapitant, NK-1 receptor antagonist, chemotherapy-induced nausea and vomiting