Data from: Efficacy and safety of bevacizumab plus erlotinib versus bevacizumab or erlotinib alone in the treatment of non-small-cell lung cancer: a systematic review and meta-analysis

Objectives: Bevacizumab and erlotinib inhibit different tumour growth
pathways, and both exhibit beneficial effects in the treatment of
non-small-cell lung cancer (NSCLC). However, the efficacy of bevacizumab
in combination with erlotinib remains controversial. Therefore, we
conducted a meta-analysis to compare combination treatment with
bevacizumab and erlotinib to bevacizumab or erlotinib monotherapy in the
treatment of NSCLC. Methods: Randomised controlled trials (RCTs) published
in PubMed, Web of Science and EMBASE were systematically reviewed. The
main outcome measures included overall survival (OS), progression-free
survival (PFS), overall response rate (ORR) and adverse events. Results
were expressed as HRs or risk ratios (RRs) with 95% CIs. Results: 5 RCTs
involving a total of 1736 patients were included in this meta-analysis.
The combination of bevacizumab and erlotinib significantly improved PFS
(HR=0.63, 95% CI 0.53 to 0.75; p=0.000) and the ORR (RR=1.91, 95% CI 1.19
to 3.06; p=0.007) in the second-line treatment of NSCLC compared with
bevacizumab or erlotinib alone. However, no significant difference in OS
was observed between the combination and monotherapy groups (HR=0.96, 95%
CI 0.83 to 1.11; p=0.573). A subgroup analysis has shown that the greatest
PFS benefit was associated with an age of <65 years(HR=0.74, 95% CI
0.57 to 0.96; p=0.026), Asian/Pacific Islander ethnicity (HR=0.23, 95% CI
0.10 to 0.54; p=0.001), Eastern Cooperative Oncology Group performance
status (ECOG PS) 1 (HR=0.82, 95% CI 0.68 to 0.98; p=0.033), stage IIIB or
IV disease (HR=0.68, 95% CI 0.57 to 0.82; p=0.000) and no history of
smoking (HR=0.48, 95% CI 0.32 to 0.71; p=0.000). The incidence of grade
3/4 adverse events such as rash and diarrhoea was higher in the
combination group than in the monotherapy group. Conclusions: The addition
of bevacizumab to erlotinib can significantly improve PFS and the ORR in
the second-line treatment of NSCLC with an acceptable and manageable risk
of rash and diarrhoea. Further well-conducted, large-scale trials are
needed to validate these findings.