Fixed combination of oral NEPA (netupitant-palonosetron) for the prevention of acute and delayed chemotherapy-induced nausea and vomiting in patients receiving multiple cycles of chemotherapy: Efficacy data from 2 randomized, double-blind phase III studies

Lee Schwartzberg, Meinolf Karthaus, Giorgia Rossi, Giada Rizzi, Maria E Borroni, Hope S Rugo, Karin Jordan, Vincent Hansen, Lee Schwartzberg, Meinolf Karthaus, Giorgia Rossi, Giada Rizzi, Maria E Borroni, Hope S Rugo, Karin Jordan, Vincent Hansen

Abstract

Aim: To assess the efficacy of oral NEPA (netupitant-palonosetron 300/0.50 mg) over multiple chemotherapy cycles.

Methods: Two randomized phase III studies evaluated a single dose of oral NEPA given on day 1 in chemotherapy-naive patients receiving anthracycline-cyclophosphamide (AC)-based (Study 1) or highly (HEC)/moderately (MEC) emetogenic chemotherapy (safety Study 2). Oral NEPA was compared with oral palonosetron 0.50 mg (Study 1) or oral aprepitant 125 mg day 1, 80 mg days 2-3/palonosetron 0.50 mg (Study 2; no formal statistical comparisons). Oral dexamethasone was administered in all treatment groups. Complete response (CR; no emesis/no rescue medication), no emesis, and no significant nausea (NSN) rates during acute (0-24 h) and delayed (>24-120 h) phases of chemotherapy cycles 1-4 in each study were evaluated.

Results: In Study 1, 1450 patients received 5969 chemotherapy cycles; in Study 2, 412 patients received 1961 chemotherapy cycles. In each study, ≥75% of patients completed 4 or more cycles. In Study 1, oral NEPA was superior to palonosetron in preventing chemotherapy-induced nausea and vomiting (CINV) in the acute and delayed phases of cycle 1, with higher rates of CR (all P < 0.05), no emesis (all P < 0.05), and NSN (delayed phase P < 0.05 cycles 1, 2, and 4) reported across 4 cycles. In Study 2, oral NEPA had numerically higher CR and NSN rates in the acute and delayed phases than aprepitant-palonosetron in MEC/HEC patients.

Conclusion: Oral NEPA was highly effective in preventing both acute and delayed CINV over multiple chemotherapy cycles of HEC, AC, and MEC regimens.

Clinical trial registration numbers: Study 1, NCT01339260; Study 2, NCT01376297.

Keywords: CINV; NEPA; delayed phase; efficacy; multiple cycles; netupitant.

Conflict of interest statement

The authors have the following conflicts of interest to disclose: LS: consultant for Helsinn Healthcare, Tesaro, Merck, and Heron. MK: consultant for Helsinn Healthcare, MSD, and Tesaro. GRo, GRi, and MEB: employees of Helsinn Healthcare. HSR: research funding from UCSF and Eisai. KJ: consultant or received honoraria from Helsinn Healthcare, Tesaro, and Merck/MSD. VH: none declared.

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Schemas of 2 international, randomized, double‐blind phase III trials: Study 1 (NCT01339260)21 and Study 2 (NCT01376297).24 a3:1 randomization NEPA: APR + PALO; the protocol also specified that 75% of patients would receive MEC and 25% HEC. AC, anthracycline‐ cyclophosphamide; APR, aprepitant; DEX, dexamethasone; HEC, highly emetogenic chemotherapy; MEC, moderately emetogenic chemotherapy; NEPA, netupitant‐palonosetron; NETU, netupitant; PALO, palonosetron
Figure 2
Figure 2
CR (no emesis, no rescue medication) rates in the delayed phase (>24‐120 h) of cycles 1‐4 in: A) Study 1 (patients receiving AC‐based chemotherapy), and B) Study 2 (patients receiving HEC or MECa). Full analysis set. aBreast cancer patients were not allowed AC‐based regimens. AC, anthracycline‐cyclophosphamide; APR, aprepitant; CR, complete response; HEC, highly emetogenic chemotherapy; MEC, moderately emetogenic chemotherapy; NEPA, netupitant‐palonosetron; PALO, palonosetron

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