Glioblastoma in the post-2021 era: Diagnostic recalibration, therapeutic innovations, and future horizons

Table 2 Summary of “randomized disappointments” with immunotherapy in unselected glioblastoma

Ref.	n	Trial number	Phase	Patient population	Design	Results
Reardon et al[35]	369	NCT02017717 Checkmate 143	Phase 3 RCT	Recurrent GBM	Nivolumab vs bevacizumab	mPFS 1.5 months vs 3.5 months, mOS 9.8 months vs 10 months, ORR 7.8% vs 23.1%
Nayak et al[32]	80	NCT02337491	Phase 2 RCT	Recurrent GBM	Pembrolizumab + bevacizumab vs pembrolizumab	PFS6 rate 26% vs 6.7%; mOS 8.8 months vs 10.3 months; ORR 20% vs 0%
Iwamoto et al[33]	60	NCT03661723	Phase 2 RCT	Recurrent GBM	Pembrolizumab + ReRT (bevacizumab naïve) vs bevacizumab continuation	mPFS 4 months each; mOS 11 months vs 7 months
Lim et al[36]	716	NCT02667587 CheckMate 548	Phase 3 RCT	Newly diagnosed GBM, MGMT methylated	Nivolumab + RT + TMZ vs placebo + RT + TMZ	mPFS 10.6 months vs 10.3 months; mOS 28.9 months vs 32.1 months
Omuro et al[37]	560	NCT02617589 CheckMate 498	Phase 3 RCT	Newly diagnosed GBM, MGMT unmethylated	Nivolumab + RT vs TMZ + RT	mPFS 6.0 months vs 6.2 months; mOS 13.4 months vs 14.9 months
Lassman et al[38]	159	NCT04396860 NRG Oncology BN007	Phase 2 RCT	Newly diagnosed GBM, MGMT unmethylated	Nivolumab + ipilimumab + RT vs TMZ + RT	mPFS 7.7 months vs 8.5 months; OS immature (approximately 13 months each)
Brown et al[39]	119	ISRCTN84434175 Ipi-Glio trial	Phase 2 RCT	Newly diagnosed GBM	Ipilimumab + TMZ vs TMZ	mPFS 10.8 months vs 12.5 months; mOS months 18.0 vs 23.0 months

RCT: Randomized controlled trial; mOS: Median overall survival; mPFS: Median progression free survival; GBM: Glioblastoma; PFS6: 6 months progression free survival; ORR: Objective response rate; RT: Radiotherapy; TMZ: Temozolomide; Ipi: Ipilimumab.