A phase two randomised trial of neratinib monotherapy versus lapatinib plus capecitabine combination therapy in patients with HER2+ advanced breast cancer |
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Authors: | Miguel Martin Jacques Bonneterre Charles E. Geyer Yoshinori Ito Jungsil Ro Istvan Lang Sung-Bae Kim Caroline Germa Jennifer Vermette Kenneth Wang Kongming Wang Ahmad Awada |
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Affiliation: | 1. Hospital Universitario Gregorio Marañón, Universidad Complutense, Calle de Maiquez 7, 28009 Madrid, Spain;2. Centre Oscar Lambret, 3 Rue Frédéric Combemale, 59000 Lille, France;3. University of Texas Southwestern Medical Center, 5303 Harry Hines Boulevard, Dallas, TX, USA;4. The Cancer Institute Hospital of JFCR, 3-8-31 Ariake, Koto ward, Tokyo, Japan;5. National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea;6. National Institute of Oncology, H-1122 Budapest Ráth György u. 7-9, Budapest, Hungary;7. Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea;8. Novartis Pharma S.A.S. Oncology Global Development, 14 Boulevard Richelieu, F-92500 Rueil-Malmaison, France;9. Pfizer Inc., 35 CambridgePark Drive, Cambridge, MA, USA;10. Bristol-Meyers Squibb Oncology, 100 Nassau Park Blvd, Princeton, NJ, USA;11. Jules Bordet Institute, Université Libre de Bruxelles, 121 bd de Waterloo, 1000 Brussels, Belgium |
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Abstract: | BackgroundThe 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.MethodsPatients received neratinib 240 mg/d continuously (n = 117) or lapatinib 1250 mg/d continuously plus capecitabine 2000 mg/m2 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).FindingsThe 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.InterpretationThe 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. |
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Keywords: | Breast phase II |
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