Temozolomide plus bevacizumab in elderly patients with newly diagnosed glioblastoma and poor performance status: An Anocef phase II trial.

2020 Background: The optimal treatment of glioblastoma multiforme (GBM) in elderly patients (age ≥70 years) with impaired functional status (Karnofsky performance status, KPS<70) remains to be established. A previous study using temozolomide (TMZ) alone suggested an increase in median overall survival (OS) compared to supportive care (25 weeks vs. 12-16 weeks, respectively). Median progression-free survival (PFS) was 16 weeks and 26% of patients became transiently capable of self-care (IK>70) (J Clin Oncol. 2011; 29: 3050-5). The present clinical trial evaluated the efficacy and safety of the combination of TMZ with bevacizumab (BV) as an initial treatment for elderly patients with GBM and KPS<70. Methods: Patients aged ≥ 70 years with KPS < 70 and a newly supratentorial GBM diagnosed by biopsy were eligible for this multicentric, prospective and non-randomised phase II trial. The primary endpoint was the OS and secondary endpoints included median PFS, quality of life, safety and cognition. Treatment consisted of TMZ 130-150 mgs/m 2 /d for 5 days every 4 weeks plus BV 10mgs/kg every 2 weeks, until 12 cycles or tumoral progression. Neither surgical resection nor radiotherapy was performed. Follow-up included clinical assessment every 2 weeks and brain MRI every 8 weeks. Results: Between October 2010 and March 2012, 66 patients (median age, 77 years; median KPS, 60) were enrolled. Median OS was 24 weeks (95% CI, 19-27.6) and median PFS was 16 weeks (95% CI, 13.1–19.3). Twenty-five patients (38%) became transiently capable of self-care (IK>70). Grade 3 and 4 haematological toxicity occurred in 13(19.6%) cases, whereas non-haematological toxicities were reported in 21(32%), including high blood pressure in 7(10%), thromboembolic events in 3(4.5%), intracerebral haemorrhage in 2(3%) and intestinal perforation in 2(3%) cases. Conclusions: This study confirms that TMZ-based treatment is of help in elderly GBM patients with poor KPS. However, the addition of bevacizumab does not appear to be of benefit in term of PFS and OS.