A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer.

Abstract

BACKGROUND:

The safety and efficacy of neratinib monotherapy were compared with that of lapatinib plus capecitabine in patients with human epidermal growth factor receptor-2-positive (HER2+), locally advanced/metastatic breast cancer and prior trastuzumab treatment.

METHODS:

Patients received neratinib 240 mg/d continuously (n=117) or lapatinib 1250 mg/d continuously plus capecitabine 2000 mg/m(2) per day on days 1-14 of each 21-d cycle (n=116). The primary aim was to demonstrate non-inferiority of neratinib for progression-free survival (PFS).

FINDINGS:

The non-inferiority of neratinib was not demonstrated when compared with lapatinib plus capecitabine (hazard ratio, 1.19; 95% confidence interval, 0.89-1.60; non-inferiority margin, 1.15). Median PFS for neratinib was 4.5 months versus 6.8 months for lapatinib plus capecitabine and median overall survival was 19.7 months versus 23.6 months. Objective response rate (neratinib, 29% versus lapatinib plus capecitabine, 41%; P=0.067) and clinical benefit rate (44% versus 64%; P=0.003) were lower for the neratinib arm but consistent with previously reported results. In both treatment arms, diarrhoea was the most frequently reported treatment-related adverse event of any grade (neratinib, 85% versus lapatinib plus capecitabine, 68%; P=0.002) and of grade 3/4 (28% versus 10%; P<0.001), but was typically managed with concomitant anti-diarrhoeal medication and/or study treatment modification. Importantly, neratinib had no significant skin toxicity.

INTERPRETATION:

The results are considered as inconclusive since neither inferiority nor non-inferiority of treatment with neratinib versus lapatinib plus capecitabine could be demonstrated. The study confirmed relevant single-agent clinical activity and acceptable overall tolerability of neratinib in patients with recurrent HER2+ advanced breast cancer.

• Authors: Miguel Martin, Jacques Bonneterre, Charles E Geyer Jr, Yoshinori Ito, Jungsil Ro, Istvan Lang, Sung-Bae Kim, Caroline Germa, Jennifer Vermette, Kenneth Wang, Kongming Wang, Ahmad Awada
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 49 Issue 18 Pg. 3763-72 (Dec 2013) ISSN: 1879-0852 [Electronic] England
• PMID: 23953056 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Quinazolines
• Quinolines
• Lapatinib
• Deoxycytidine
• Capecitabine
• ERBB2 protein, human
• Receptor, ErbB-2
• neratinib
• Fluorouracil

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Capecitabine
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Diarrhea (chemically induced)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Kaplan-Meier Estimate
• Lapatinib
• Middle Aged
• Nausea (chemically induced)
• Quinazolines (administration & dosage, adverse effects)
• Quinolines (adverse effects, therapeutic use)
• Receptor, ErbB-2 (metabolism)
• Treatment Outcome
• Vomiting (chemically induced)