Bevacizumab in combination with TMZ in patients with recurrent GBM: Final OS and PFS analysis.

Abstract

2087 Background: BEV provides a consistent clinical benefit in the treatment of relapsing GBM in terms of a delayed progression and increased median overall survival compared to historical controls. The aim of this study is to evaluate the efficacy and toxicity profile of the combination of BEV with dose dense TMZ, reporting the final results of PFS, OS and the toxicity experienced. Methods: A phase II multicenter, national, open-label study in pts diagnosed of recurrent GBM treated with BEV 10 mg/kg day q2w and TMZ 150 mg/m2 days 1-7 and 15-21 q28d d until disease progression or unacceptable toxicity or medical decision, as first line of treatment all pts received radiotherapy and at least 3 cycles of adjuvant TMZ. This study evaluates efficacy by PFS as primary endpoint and as secondary endpoints: OS, RR based on the adapted MacDonald criteria and toxicity profile (NCI CTC v3.0). Results: From June 10 to July 11, 32 evaluable pts were recruited in 8 sites. The baseline characteristics were as follows: 17 males and 15 females, median age 57.5 y (29-74), ECOG PS 0: 25%, PS 1: 50% and PS 2: 25%, 44% patients had gross total resection, 50% had subtotal resection and 6% biopsy only, MGMT promotor was methylated in 12 pts, unmeth in 6 pts and missing in 14 pts. The median number of TMZ or BEV cycles administered across all patients was 4 (TMZ range 1-9 and BEV range 1-25) The median PFS was 4.4 m [IC 95% (3.7 – 5.6)]. The 6m-PFS probability was 29.25%. The median OS (75% events) was 7.5 m[IC 95% (5.98 – 9.11)]. No significant association with MGMT status was found in terms of OS or PFS. BEV related AEs have been reported in 56.2% of the population being most of them mild or moderate. Grade 3-4 most frequent toxicity: lymphopenia 31% and fatigue 12.5%. Six of 32 pts were long term survivors, in this population the median PFS was 9.8 m [IC 95% (8.2 – 24.4)] and median OS (50% events) was 15.9 m [IC 95 %( 9.2 – NA)], no differences in baseline characteristics were identified in comparison with total population. The median number of TMZ cycles administered was 4 and median BEV cycles were 9. Conclusions: Although the combination don’t met the previous reported activity of BEV, 19% of patients had longer survivals which suggest the need to identify patients that benefit for this treatment. Clinical trial information: NCT01115491.