The researchers tested whether adjunct Erlotinib ( Tarceva ), a direct and reversible EGFR tyrosine kinase inhibitor, could have synergistic or additive antitumor effects when used with Sorafenib ( Nexavar ) in patients with advanced hepatocellular carcinoma. The approach did not improve overall survival or time to progression.
This phase III, randomized, double-blind, placebo-controlled trial of Sorafenib plus Erlotinib enrolled 720 patients with advanced hepatocellular carcinoma aged 18 or more years, ECOG performance status ( PS ) 0-1 and Child-Pugh class A. Patients were stratified by ECOG PS of 0 or 1, macroscopic vascular invasion and/or presence of extrahepatic spread, smoking status ( current, former or never ) and by region: the Americas and Europe versus South Africa and Asia-Pacific.
The patients were randomized 1:1 to receive either continuous treatment with oral Sorafenib 400 mg bid plus Erlotinib 150 mg daily or Sorafenib 400 mg bid plus placebo 150 mg daily and monitored every 6 weeks by CT scans.
The primary endpoint of the study, defined as 33% of increase in the overall survival, was not met in this study.
Median overall survival in the 362 patients receiving the Sorafenib / Erlotinib was 9.5 months compared with 8.5 months in the Sorafenib / placebo arm.
Time to progression also did not vary significantly between treatment arms and was 3.2 compared with 4.0 months, with Sorafinib / Erlotinib and Sorafenib / placebo, respectively.
No significant regional differences in overall survival or time to progression were noted.
The disease control rates of 43.92% and 52.51% favored the Sorafenib / placebo arm.
The median treatment duration of 2.8 and 4.0 months was longer with Sorafenib / placebo, which reflected the percentage of patients withdrawing after completing one or fewer treatment cycles; the withdrawal rate was 34.0% in the Sorafenib / Erlotinib arm compared with 23.8% with Sorefenib / placebo.
The rates of treatment-emergent and drug-related adverse events were similar between arms; and treatment-emergent and drug-related serious adverse events were also similar ( 58.0% versus 54.6% and 21.0% versus 22.8% in the Sorafenib / Erlotinib and Sorafenib / placebo arms, respectively ).
No new or unexpected toxicities were observed between combination treatment and Sorafenib or Erlotinib alone.
The results have indicate that Erlotinib added to Sorafenib do not improve overall survival or time to progression over sole Sorafenib in patients with advanced hepatocellular carcinoma.
Safety profiles were similar between the two treatment groups and consistent with those of each individual agent; however the withdrawal rate was higher in the Erlotinib / Sorafenib arm, with fewer patients completing one or more cycles. ( Xagena )
Source: Congress of the European Society for Medical Oncology ( ESMO ), 2012