Efficacy of NEPA (netupitant/palonosetron) across multiple cycles of chemotherapy in breast cancer patients: A subanalysis from two phase III trials

Breast. 2017 Jun:33:76-82. doi: 10.1016/j.breast.2017.02.017. Epub 2017 Mar 10.

Abstract

Objectives: Breast cancer (BC) patients represent a high-risk population for experiencing chemotherapy-induced nausea and vomiting (CINV), since they frequently receive highly emetogenic anthracycline-cyclophosphamide-based (AC) chemotherapy, and are often female and young, two predisposing risk factors for CINV. Guidelines recommend the combination of a neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine-3 RA (5-HT3RA), and dexamethasone (DEX) for CINV prophylaxis in AC-treated patients. This post-hoc analysis evaluated the efficacy of NEPA, a fixed combination of netupitant (NETU [NK1RA]) and palonosetron (PALO [5-HT3RA]) in BC patients from two phase III studies.

Methods: Overall, 1460 BC patients received AC (Study 1) or non-AC (Study 2) therapy over 6060 cycles. Randomized patients received DEX with either NEPA or oral PALO (Study 1), or NEPA or aprepitant+oral PALO (Study 2) before chemotherapy.

Results: In AC-receiving patients, overall complete response (CR) rates with NEPA+DEX were statistically significantly higher than oral PALO+DEX rates (cycles 1-4: 73.9% vs 65.9%, 80.0% vs 66.0%, 83.6% vs 69.9%, 83.6% vs 74.4%, respectively). Overall, no significant nausea (NSN) rates were also superior with NEPA+DEX vs oral PALO+DEX (respectively, 74.2%-79.9% vs 68.5%-74.9%). A greater proportion of NEPA+DEX patients experienced "no-impact-on-daily-life" due to CINV (78.4% vs 71.4%) in cycle 1. In non-AC-receiving patients, prophylaxis with NEPA+DEX resulted in high CR and NSN rates across 1-4 chemotherapy cycles; no formal comparison with the control arm was performed.

Conclusion: NEPA+DEX administered as a single dose is an effective option for preventing CINV in BC patients receiving AC and non-AC, across multiple chemotherapy cycles.

Clinical trials registration numbers: Study 1: NCT01339260, Study 2:NCT01376297.

Keywords: Antiemetic; Breast cancer; CINV; NEPA; Netupitant; Palonosetron.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Anthracyclines / adverse effects
  • Antiemetics / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms / drug therapy*
  • Clinical Trials, Phase III as Topic
  • Cyclophosphamide / adverse effects
  • Dexamethasone / administration & dosage
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Isoquinolines / administration & dosage*
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / prevention & control*
  • Pyridines / administration & dosage*
  • Quinuclidines / administration & dosage*
  • Treatment Outcome
  • Vomiting / chemically induced
  • Vomiting / prevention & control*
  • Young Adult

Substances

  • Anthracyclines
  • Antiemetics
  • Drug Combinations
  • Isoquinolines
  • Pyridines
  • Quinuclidines
  • netupitant, palosentron drug combination
  • Dexamethasone
  • Cyclophosphamide

Associated data

  • ClinicalTrials.gov/NCT01339260
  • ClinicalTrials.gov/NCT01376297