A multi-institutional phase II study of the efficacy and tolerability of lapatinib in patients with advanced hepatocellular carcinomas

Tanios Bekaii-Saab, Joseph Markowitz, Nichole Prescott, Wolfgang Sadee, Nyla Heerema, Lai Wei, Zunyan Dai, Audrey Papp, Angela Campbell, Kristy Culler, Catherine Balint, Bert O'Neil, Ruey Min Lee, Mark Zalupski, Janet Dancey, Helen Chen, Michael Grever, Charis Eng, Miguel Villalona-Calero

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Background: Hepatocellular carcinoma (HCC) is on the rise worldwide. HCC responds poorly to chemotherapy. Lapatinib is an inhibitor of epidermal growth factor receptor and HER2/NEU both implicatedin hepatocarcinogenesis. This trial was designed to determine the safety and efficacy of lapatinib in HCC. Methods: A Fleming phase II design with a single stage of 25 patients with a 90% power to exclude a true response rate of <10% and detect a true response rate of ≥30% was used. The dose of lapatinib was 1,500 mg/day administered orally in 28-day cycles. Tumor and bloodspe cimens were analyzedf or expression of HER2/NEU/CEP17 and status of downstream signal pathway proteins. Results: Twenty-six patients with HCC enrolled on this study. Nineteen percent had one prior therapy. Most common toxicities were diarrhea (73%), nausea (54%), and rash (42%). No objective responses were observed. Ten (40%) patients had stable disease as their best response including six (23%) with stable disease lasting >120 days. Median progression-free survival was 1.9 months and median overall survival was 12.6 months. Patients who developed a rash had a borderline statistically significant longer survival. Tissue and blood specimens were available on >90% of patients. No somatic mutations in EGFR (exons 18-21) were found. In contrast to our previous findings, we did not find evidence of HER2/NEU somatic mutations. PTEN, P-AKT, andP70S6 K expression did not correlate with survival. Conclusions: Lapatinib is well-toleratedbut seems to benefit only a subgroup of patients for whom predictive molecular or clinical characteristics are not yet fully defined.

Original languageEnglish (US)
Pages (from-to)5895-5901
Number of pages7
JournalClinical Cancer Research
Issue number18
StatePublished - Sep 15 2009

ASJC Scopus subject areas

  • Medicine(all)


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