A Multi-Institutional Phase II Study of the Efficacy and Tolerability of Lapatinib in Patients with Advanced Hepatocellular Carcinomas

• Published in: Clinical cancer research 2009-09, Vol.15 (18), p.5895-5901
• Main Authors: BEKAII-SAAB, Tanios, MARKOWITZ, Joseph, BALINT, Catherine, O'NEIL, Bert, LEE, Ruey-Min, ZALUPSKI, Mark, DANCEY, Janet, CHEN, Helen, GREVER, Michael, ENG, Charis, VILIALONA-CALERO, Miguel, PRESCOTT, Nichole, SADEE, Wolfgang, HEEREMA, Nyla, LAI WEI, ZUNYAN DAI, PAPP, Audrey, CAMPBELL, Angela, CULLER, Kristy
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Carcinoma, Hepatocellular - drug therapy; Disease Progression; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; EGFR; Female; Gastroenterology. Liver. Pancreas. Abdomen; hepatocellular; Humans; Lapatinib; Liver Neoplasms - drug therapy; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Predictive Value of Tests; Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - therapeutic use; Survival Rate; Tumors
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-0465

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 implicated in 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 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, and P70S6K expression did not correlate with survival. Conclusions: Lapatinib is well-tolerated but seems to benefit only a subgroup of patients for whom predictive molecular or clinical characteristics are not yet fully defined. (Clin Cancer Res 2009;15(18):5895–901)