Efficacy of bevacizumab combined with erlotinib for advanced hepatocellular carcinoma: a single-arm meta-analysis based on prospective studies.

BACKGROUND

The efficacy of bevacizumab combined with erlotinib (B + E) for the treatment of advanced hepatocellular carcinoma, especially for sorafenib-refractory patients, has been observed and evaluated in several trials. We conducted this single arm meta-analysis to generally assess the benefit and risk with B + E for advanced hepatocellular carcinoma.

METHODS

The PubMed, Cochrane Library, Embase, ScienceDirect, Web of Science and Scopus databases were searched for related studies. The main outcomes were objective response rate (ORR), disease control rate (DCR), overall survival (OS), progression-free survival (PFS) and adverse effects (AEs).

RESULTS

Eight phase II clinical trials including 342 hepatocellular carcinoma patients were analyzed. The pooled ORR was 12.6% (95% CI: 6.3-19.0%), and the pooled DCR was 54.5% (95% CI: 48.9-66.8%). The 16-week PFS rate was 50.2% (95% CI: 38.2-62.2%). The 6- and 12-month OS rates were 77.8% (95% CI: 71.3-84.2%) and 44.9% (95% CI: 36.8-53.0%). The main grade 3-4 AEs were fatigue (11.9%), diarrhea (9.0%), hypertension (6.7%), acne (5.8%) and hemorrhage (5.3%). The only RCT showed that the B + E regimen had a consistent response and equable median OS but fewer toxicities (grade 3-4 AEs: 19% vs. 27%) than sorafenib. Subgroup analysis showed that as a second-line treatment, the B + E regimen had substantial value with a favorable PFS-16w (P = 0.012), OS-12 m (P = 0.048) and a favorable tendency of ORR (P = 0.089), but obvious toxicities in the second-line setting could not be neglected.

CONCLUSION

Bevacizumab combined with erlotinib is effective for treating hepatocellular carcinoma patients, especially sorafenib-refractory patients. More well-designed and large-scale RCTs are warranted to prove our findings.