ROLe Of beVacizumab iN NewLy diagNOsed gLiObLastOma

نویسنده

  • Roger Y. Tsang
چکیده

Chemoradiation (CRT) with temozolomide (TMZ/CRT+TMZ) is the standard of care for newly diagnosed glioblastoma (GBM). This phase III trial, conducted by the Radiation Therapy Oncology Group (RTOG), North Central Cancer Treatment Group (NCCTG) and Eastern Cooperative Oncology Group (ECOG), evaluated whether adding bevacizumab (Bev) to standard CRT improves overall survival (OS) or progression-free survival (PFS) in this patient population. Neurologically stable patients older than 18 years with Karnofsky performance score (KPS) ≥60 and >1cm tumour tissue block were randomized to standard CRT plus placebo (Arm 1) or standard CRT plus intravenous Bev 10 mg/kg every 2 weeks (Arm 2). Experimental treatment began at week 4 of radiation and then through 6 to 12 cycles of maintenance chemotherapy. Primary endpoints were OS and PFS, with significance levels of 0.023 and 0.002, respectively. At progression, treatment was unblinded and patients were allowed to cross over or continue Bev. Symptom, quality of life (QOL) and neurocognitive (NCF) testing was performed in most patients. Secondary analyses evaluated impact of methylguanine-methyltransferase enzyme (MGMT) methylation (meth) and prognostic 9-gene signature status. Out of 978 registered patients, 637 were randomized. Inadequate tissue (n=105) and blood on imaging (n=40) were key reasons for nonrandomization. No difference was found between Arm 1 and Arm 2 for OS (median 16.1 vs 15.7 months; p=0.11). PFS was extended for Arm 2 (10.7 months vs 7.3 months in Arm 1; p=0.004). Patients with MGMT meth had superior OS (23.2 vs 14.3 months; p<0.001) and PFS (14.1 vs 8.2 months; p<0.001). Neither the 9-gene signature nor MGMT predicted selective benefit for Bev treatment, but best-prognosis patients (MGMT meth, favourable 9-gene) had a worse survival trend with Bev (15.7 vs 25 months; p=0.08). To date, 128 patients were unblinded on Arm 1 (salvage Bev in 86) and 87 patients on Arm 2 (continued Bev in 39). Increased grade ≥3 toxicity was seen with Bev, mostly neutropenia, hypertension and deep vein thrombi/pulmonary embolism (DVT/PE). The authors concluded that the addition of Bev did not improve OS for newly diagnosed GBM patients; while it did improve PFS, this did not reach the significance criterion. MGMT and 9-gene profile did not identify selective benefit, but risk subset results suggested strongly against the upfront use of Bev in the best-prognosis patients. Full interpretation of the PFS results incorporating symptom burden, QOL and NCF is ongoing.

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تاریخ انتشار 2013