SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma.

Abstract

PURPOSE:

To compare the clinical outcomes of sorafenib plus either erlotinib or placebo in patients with advanced hepatocellular carcinoma (HCC) in a multicenter, multinational, randomized, phase III trial.

PATIENTS AND METHODS:

Patients with advanced HCC and underlying Child-Pugh class A cirrhosis, who were naive to systemic treatment (N = 720), were randomly assigned to sorafenib plus either erlotinib (n = 362) or placebo (n = 358). The primary end point was overall survival (OS).

RESULTS:

Median OS was similar in the sorafenib plus erlotinib and sorafenib plus placebo groups (9.5 v 8.5 months, respectively; hazard ratio [HR], 0.929; P = .408), as was median time to progression (3.2 v 4.0 months, respectively; HR, 1.135; P = .18). In the sorafenib/erlotinib arm versus the sorafenib/placebo arm, the overall response rate trended higher (6.6% v 3.9%, respectively; P = .102), whereas the disease control rate was significantly lower (43.9% v 52.5%, respectively; P = .021). The median durations of treatment with sorafenib were 86 days in the sorafenib/erlotinib arm and 123 days in the sorafenib/placebo arm. In the sorafenib/erlotinib and sorafenib/placebo arms, the rates of treatment-emergent serious AEs (58.0% v 54.6%, respectively) and drug-related serious AEs (21.0% v 22.8%, respectively) were similar. AEs matched the known safety profiles of both agents, but rates of rash/desquamation, anorexia, and diarrhea were higher in the sorafenib/erlotinib arm, whereas rates of alopecia and hand-foot skin reaction were higher in the sorafenib/placebo arm. Withdrawal rates for AEs during cycles 1 to 3 were higher in the sorafenib/erlotinib arm.

CONCLUSION:

Adding erlotinib to sorafenib did not improve survival in patients with advanced HCC.

• Authors: Andrew X Zhu, Olivier Rosmorduc, T R Jeffry Evans, Paul J Ross, Armando Santoro, Flair Jose Carrilho, Jordi Bruix, Shukui Qin, Paul J Thuluvath, Josep M Llovet, Marie-Aude Leberre, Markus Jensen, Gerold Meinhardt, Yoon-Koo Kang
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 6 Pg. 559-66 (Feb 20 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 25547503 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Phenylurea Compounds
• Placebos
• Quinazolines
• Niacinamide
• Sorafenib
• Erlotinib Hydrochloride

Topics

• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Double-Blind Method
• Erlotinib Hydrochloride
• Female
• Humans
• Liver Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Niacinamide (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Phenylurea Compounds (administration & dosage, adverse effects, therapeutic use)
• Placebos
• Quinazolines (administration & dosage, adverse effects)
• Sorafenib