Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial

Abstract

We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide. In the TMZ + BEV arm, bevacizumab (10 mg/kg) was added on days 1 and 15 of each neoadjuvant cycle and on days 1, 15 and 30 of concurrent treatment. The primary endpoint was investigator-assessed response to neoadjuvant treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the impact on outcome of MGMT methylation in tumor and serum. One hundred and two patients were included; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response. Results favored the TMZ + BEV arm in terms of objective response (3 [6.7 %] vs. 11 [22.9 %]; odds ratio 4.2; P = 0.04). PFS and OS were longer in the TMZ + BEV arm, though the difference did not reach statistical significance. MGMT methylation in tumor, but not in serum, was associated with outcome. More patients experienced toxicities in the TMZ + BEV than in the TMZ arm (P = 0.06). The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity.

The prognosis for patients with newly diagnosed glioblastoma receiving bevacizumab combination therapy: a meta-analysis

“…A random-effects model was used to pool the OS data. 10 , 11 , 13 – 15 The pooled data showed that a BEV agent plus chemotherapy did not improve the OS (HR =0.91, 95% CI =0.76–1.08, P =0.28) than the control treatment ( Figure 6 ).…”

“…Based on the criteria described in the “Methods” section, 10 publications were evaluated in more detail, but some did not provide enough detail of the outcomes of two approaches. Therefore, we had a final total of six RCTs 10 – 15 assessing the value of BEV in patients with newly diagnosed GB. The search process is described in Figure 1 .…”

“…Pooling the PFS data from five studies 10 , 11 , 13 – 15 showed that BEV prolonged the PFS (HR =0.69, 95% CI =0.63–0.77, P <0.00001) compared with the control group ( Figure 2 ).…”

“…At the time of the approval of BEV in recurrent disease, several randomized controlled trials (RCTs) were launched to investigate the value of BEV in addition to the treatment for newly diagnosed GB. 10 – 15 Treatment combined with BEV exhibited significant activity in PFS for newly diagnosed GB patients, while further evaluation is needed to assess disease progression after antiangiogenic therapy.…”

Staged Image-guided Robotic Radiosurgery and Deferred Chemotherapy to Treat a Malignant Glioma During and After Pregnancy

“…These results reconfirmed the potential benefit of combined TMZ, BEV, and CK-SRT. A recent study by Balana et al compared BEV-plus-TMZ to TMZ alone, enrolling 102 patients [ 7 ]. The authors showed that PFS and OS were longer in the TMZ + BEV arm, although the difference did not reach statistical significance.…”