Zosia Chustecka

October 11, 2012

October 11, 2012 (Vienna, Austria) — Adding erlotinib (Tarceva) to sorafenib (Nexavar) provides no benefit in patients with hepatocellular carcinoma (HCC), according to a large phase 3 study of patients with hepatocellular carcinoma (HCC), known as Sorafenib and Erlotinib Randomized Trial Protocol for the Treatment of Patients With Hepatocellular Carcinoma (SEARCH). Therefore, for the time being, sorafenib monotherapy remains the standard of care in unresectable HCC, experts said here at the 2012 European Society for Medical Oncology Congress.

Sorafenib is currently the only drug approved for use in liver cancer. The 2007 approval was granted on the basis of results from the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial (N Engl J Med. 2008;359:378-390). It showed that sorafenib, compared with placebo, prolonged overall survival in 602 patients (10.7 vs 7.9 months; hazard ratio [HR], 0.69; P < .001).

The hope was that adding another targeted agent would improve these results and that the 2 drugs would act synergistically, explained Manfred Lutz MD, from CaritasKlinikum St. Theresia in Saarbrücken, Germany, who acted as discussant for the study.

Erlotinib has shown some promising single-agent activity in liver cancer in 2 phase 2 clinical trials, where it improved median overall survival to 10.75 months and 13.00 months, compared with around 7 months in the control groups, he noted. "So the rationale behind the trial can be defended," he added.

Results from SEARCH were presented by Andrew Zhu, MD, PhD, from the Massachusetts General Hospital in Boston. It involved 720 patients with advanced liver cancer, and compared sorafenib (400 mg twice daily) monotherapy (administered with a matching placebo) with the combination of sorafenib plus erlotinib (150 mg once daily).

The was no significant difference in median overall survival — the primary end point — between the combination and the monotherapy (9.5 vs 8.5 months; HR, 0.929; P =.204).

For secondary end points, there was no significant difference between the combination and the monotherapy in the time to progression (3.2 vs 4.0 months; HR 1.135; P = .91). The overall response rate was significantly higher with the combination (7% vs 4%; P = .051), but the disease control rate was significantly higher with the monotherapy (44% vs 53%; P = .0104). In addition, the adverse-event profile was a little worse with the combination, particularly for rash and diarrhea, Dr. Zhu noted.

Dr. Lutz noted that the 8.5-month overall survival seen with sorafenib monotherapy in SEARCH was less than the 10.7 months seen in the SHARP trial, but the 2 trials had different proportions Asian patients and of hepatitis-positive patients.

Both Dr. Zhu and Dr. Lutz conclude that SEARCH was a negative trial, and that sorafenib monotherapy remains the standard of care in HCC.

The SEARCH trial was funded by Bayer, the manufacturer of sorafenib.

2012 European Society for Medical Oncology (ESMO) Congress: Abstract LBA2. Presented September 30, 2012.