CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer

Xavier Pivot, Alexey Manikhas, Bogdan Zurawski, Ewa Chmielowska, Boguslawa Karaszewska, Rozenn Allerton, Stephen Chan, Alessandra Fabi, Paolo Bidoli, Stefania Gori, Eva Ciruelos, Magdolna Dank, Lajos Hornyak, Sara Margolin, Arnd Nusch, Roma Parikh, Fareha Nagi, Michelle DeSilvio, Sergio Santillana, Ramona F. SwabyVladimir Semiglazov

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: CEREBEL compared the incidence of CNS metastases as first site of relapse in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer receiving lapatinib-capecitabine or trastuzumab-capecitabine. Patients and Methods: Patients without baseline CNS metastases were randomly assigned (1:1) to receive lapatinib-capecitabine (lapatinib 1,250 mg per day; capecitabine 2,000 mg/m2 per day on days 1 to 14 every 21 days) or trastuzumab-capecitabine (trastuzumab loading dose of 8 mg/kg followed by an infusion of 6 mg/kg every 3 weeks; capecitabine 2,500 mg/m2 per day on days 1 to 14 every 21 days). The primary end point was incidence of CNS metastases as first site of relapse. Secondary end points included progression-free survival (PFS) and overall survival (OS). Results: The study was terminated early with 540 enrolled patients (271 received lapatinib-capecitabine, and 269 received trastuzumab-capecitabine). Incidence of CNS metastases as first site of relapse was 3% (eight of 251 patients) for lapatinib-capecitabine and 5% (12 of 250 patients) for trastuzumab-capecitabine (treatment differences, -1.6%; 95% CI, -2% to 5%; P = .360). PFS and OS were longer with trastuzumab-capecitabine versus lapatinib-capecitabine (hazard ratio [HR] for PFS, 1.30; 95% CI, 1.04 to 1.64; HR for OS, 1.34; 95% CI, 0.95 to 1.64). Serious adverse events were reported in 13% (34 of 269 patients) and 17% (45 of 267 patients) of patients in the lapatinib-capecitabine and trastuzumab-capecitabine arms, respectively. Conclusion: CEREBEL is inconclusive for the primary end point, and no difference was detected between lapatinb-capecitabine and trastuzumab-capecitabine for the incidence of CNS metastases. A better outcome was observed with trastuzumab-capecitabine in the overall population. However, lapatinib-capecitabine efficacy may have been affected by previous exposure to a trastuzumab regimen and/or when treatment was given as first- or second-line therapy in the metastatic setting.

Original languageEnglish
Pages (from-to)1564-1573
Number of pages10
JournalJournal of Clinical Oncology
Volume33
Issue number14
DOIs
Publication statusPublished - May 10 2015

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Fingerprint Dive into the research topics of 'CEREBEL (EGF111438): A phase III, randomized, open-label study of lapatinib plus capecitabine versus trastuzumab plus capecitabine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer'. Together they form a unique fingerprint.

Cite this