乌鸦传媒

PARIS -- Patients with advanced hepatocellular carcinoma receiving both and kinase inhibitor sorafenib (Nexavar) as part of palliative care showed no significant improvement in survival versus patients treated with sorafenib alone, according to a late-breaking trial report here.

Median survival for patients treated with both therapies was 12.13 months versus 11.47 months with sorafenib alone (HR 1.0067, P=0.951) among an intent-to-treat population, reported Jens Ricke, MD, of Ludwig-Maxilimilans University Munich in Germany.

However, there was a significant difference in survival among subgroups of patients with less severe disease who received both treatments.

This study was part of a prospective, phase III multi-center randomized controlled trial conducted in Europe and Turkey that comprised diagnostic, local ablation and palliative studies. Based on the result of the diagnostic study, patients were assigned to either the local ablation cohort or the palliative cohort, the authors wrote.

Results from the palliative cohort were presented at a press conference at the International Liver Congress, the annual meeting of the (EASL).

Overall, 424 patients were assigned to the palliative arm -- 216 randomized to receive selective internal radiation therapy and sorafenib and 208 assigned to receive sorafenib alone. The safety population was comprised of 159 patients who received both treatments and 197 who received sorafenib, while the per protocol population was 114 who received both treatments "with no major deviations" and 174 who received sorafenib "with no major deviations." Ricke noted protocol violations were compliance issues on the part of the investigators, such as certain investigators who were supposed to administer both treatments feeling that it was not necessary for patients to receive sorafenib.

There were no significant between-group differences in patient characteristics. Median age of patients in both groups was 66, around 85% were men and 80% had cirrhosis. Around two-thirds of each group were . There was also no difference in serious adverse treatment events between the two groups.

Because the combination therapy did not result in a significant improvement in survival in the compared to sorafenib alone, Ricke acknowledged "the primary endpoint had not been met." However, he noted a median survival improvement of 3 months in the per-protocol population, even though it was non-significant (14.07 SIRT/sorafenib versus 11.14 sorafenib, P=0.253).

The pre-planned per protocol subanalyses did show significant improvement with the combination of the two treatments in certain patient groups:

• Non-cirrhotic patients: (22.16 SIRT/sorafenib versus 9.93 sorafenib, HR 0.4645, P=0.015)
• Patients with non-alcoholic etiology: (15.32 versus 11.08, respectively, HR 0.06321, P=0.010)
• Patients age <65: (18.57 versus 11.34, respectively, HR 0.06519, P=0.048)

Ricke characterized the subgroup analyses as "hypothesis-generating," because they "suggested clinical benefits" for certain groups of patients.

David Victor, MD, of Houston Methodist in Houston, Texas, agreed -- telling 乌鸦传媒 that this study suggests it may not be good to look at patients who have advanced cancer as one group across the board.

"Less advanced patients might benefit from more aggressive treatment, but applying one strategy across patients might not be a good strategy," said Victor, who was not involved with the research. "This suggests careful patient selection may show a benefit."

But finding patients early would be the best bet, David Bernstein, MD, of Northwell Health in Manhasset, N.Y., advised.

"This study speaks to the importance of early diagnosis and screening for cancer in all these patients who are cirrhotic," he explained to 乌鸦传媒. Bernstein was not involved with the research. "If we find them when they're single lesions and small lesions, we can do a lot for them. Once you have a lot of larger lesions, our choice of therapies are pretty limited, life expectancy goes way down and you can't do a lot."

Comment