RTOG 0825: trial | Bending the Curve: Trial by Trial

RTOG 0825

Temozolomide and radiation therapy with or without bevacizumab in newly diagnosed glioblastoma (RTOG 0825)

Population

Adults with centrally confirmed newly diagnosed glioblastoma; 978 registered and 637 randomised

Design

Randomised, double-blind, placebo-controlled phase 3 trial: radiotherapy (60 Gy) and daily temozolomide with bevacizumab or placebo starting in week 4 of radiotherapy and continued for up to 12 cycles of maintenance chemotherapy; designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary endpoints

Primary endpoint

OS, PFS

Arms

Bevacizumab plus radiotherapy-temozolomide (experimental): Bevacizumab with radiotherapy (60 Gy) and daily temozolomide, then maintenance chemotherapy for up to 12 cycles; schedule details not in the abstract
Placebo plus radiotherapy-temozolomide (control): Placebo with radiotherapy (60 Gy) and daily temozolomide, then maintenance chemotherapy for up to 12 cycles; schedule details not in the abstract

People

Gilbert MR

OSHR 1.13Δ median OS−0.4 monthsPFSHR 0.79Δ median PFS+3.4 months

Show the numbers

Results reported for RTOG 0825
Endpoint	Analysis	Bevacizumab plus radiotherapy-temozolomide	Placebo plus radiotherapy-temozolomide	Effect
OSRandomised patients (n=637); analysis population not stated in the abstractOverall survival (coprimary endpoint)	primaryGilbert 2014	median 15.7 months	median 16.1 months	HR 1.13Hazard ratio for death in the bevacizumab group as printed in the abstract, without a confidence interval or P value; the abstract reports no significant difference.
PFSRandomised patients (n=637); analysis population not stated in the abstractProgression-free survival (coprimary endpoint)	primaryGilbert 2014	median 10.7 months	median 7.3 months	HR 0.79Hazard ratio as printed in the abstract, without a confidence interval or P value; the abstract states progression-free survival was prolonged but did not reach the prespecified improvement target.

Results reported for RTOG 0825
Endpoint	Analysis	Bevacizumab plus radiotherapy-temozolomide	Placebo plus radiotherapy-temozolomide	Effect
OSRandomised patients (n=637); analysis population not stated in the abstractOverall survival (coprimary endpoint)	primaryGilbert 2014	median 15.7 months	median 16.1 months	HR 1.13Hazard ratio for death in the bevacizumab group as printed in the abstract, without a confidence interval or P value; the abstract reports no significant difference.
PFSRandomised patients (n=637); analysis population not stated in the abstractProgression-free survival (coprimary endpoint)	primaryGilbert 2014	median 10.7 months	median 7.3 months	HR 0.79Hazard ratio as printed in the abstract, without a confidence interval or P value; the abstract states progression-free survival was prolonged but did not reach the prespecified improvement target.

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Bevacizumab plus radiotherapy-temozolomide (experimental)
Placebo plus radiotherapy-temozolomide (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Bevacizumab plus radiotherapy-temozolomide	Placebo plus radiotherapy-temozolomide
0	100.0%	100.0%
10	64.3%	65.0%
20	41.4%	42.3%
30	26.6%	27.5%
40	17.1%	17.9%

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Bevacizumab plus radiotherapy-temozolomide (experimental)
Placebo plus radiotherapy-temozolomide (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Bevacizumab plus radiotherapy-temozolomide	Placebo plus radiotherapy-temozolomide
0	100.0%	100.0%
7	63.5%	51.4%
13	43.1%	29.1%
20	27.4%	15.0%
27	17.4%	7.7%

Appears in

2014 Bevacizumab added to chemoradiation does not improve survival

Sources

Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):699-708.
PubMed DOI