First-line bevacizumab contributes to survival improvement in glioblastoma patients complementary to temozolomide

Introduction: First-line bevacizumab (BEV) is now available as a treatment option for glioblastoma patients with severe clinical conditions in Japan. However, the survival benefits remain controversial. To elucidate these potential survival benefits, we retrospectively analyzed survival in glioblastoma patients receiving BEV. Methods: We analyzed survival in 120 patients with IDH-wild type glioblastoma treated from 2002 to 2018. Overall survival (OS) was assessed in three treatment era subgroups [pre-temozolomide (TMZ), TMZ, and TMZ–BEV], and the correlations of prognostic factors with survival were evaluated. Results: An improvement in survival was observed after BEV approval (median OS in the pre-TMZ, TMZ, and TMZ–BEV eras: 14.6, 14.9, and 22.1 months, respectively). A Cox proportional hazards model identified extent of resection and MGMT methylation status as significant prognostic factors in the TMZ era; however, these factors were not significant in the TMZ–BEV era. In subgroup analyses, patients with MGMT methylation had improved OS after TMZ introduction (pre-TMZ vs. TMZ, 18.5 vs. 28.1 months; P = 0.13), and those without MGMT methylation had significantly increased OS after BEV approval (TMZ vs. TMZ–BEV, 12.2 vs. 16.7 months; P = 0.04). Conclusions: Our findings imply that optional first-line administration of BEV can overcome the impact of conventional risk factors and prolong survival complementary to TMZ. The patient subgroups benefitting from TMZ and BEV did not seem to overlap, and stratification based on risk factors, including MGMT methylation status, might be effective for selecting patients in whom BEV should be preferentially used as a first-line therapy.