Prolonged survival after bevacizumab rechallenge in glioblastoma patients with previous response to bevacizumab^†

Background: The use of bevacizumab for recurrent glioblastoma is controversial. Here we show data on patients who responded to bevacizumab, then stopped bevacizumab for any reason other than progression and were rechallenged with bevacizumab at the time of subsequent progression.

Methods: This retrospective study included 28 patients, classified in 2 cohorts: those for whom the first exposure to bevacizumab (BEV-1) was first-line treatment for newly diagnosed glioblastoma (Bev-F; N = 12) and those for whom BEV-1 was second- or third-line treatment for recurrent disease after standard treatment (Bev-S; N = 16).

Results: All patients received standard radiotherapy plus temozolomide. Bev-F patients also received concomitant bevacizumab. All 28 patients received a total of 57 treatment lines with bevacizumab (12 first-line and 45 second- or further-line). Twenty-nine lines were rechallenges (BEV-2 [N = 26] or BEV-3 [N = 3]). Objective response to rechallenge was 58.6% and clinical benefit was 89.6%. Overall survival (OS) was 55 months for RPA class IV and 26.7 months for RPA class V patients (P = .01). OS was 26.7 months for Bev-F patients and 52.1 months for Bev-S patients (P = .004). Post-progression survival was 20 months for Bev-F patients and 39.6 months for Bev-S patients (HR = 0.26; P = .007).

Conclusion: This is the largest study to examine the impact of a bevacizumab rechallenge in glioblastoma patients who had responded to previous bevacizumab treatment but who stopped before progression. Our findings indicate that these patients can attain a second response or clinical benefit from re-introduction of bevacizumab. The potential benefit from intermittent versus continuous treatment warrants comparison in clinical trials.