Overall Management > Methodology

Meeting Abstract

K. V. Ballman, K. A. Jaeckle, P. D. Brown, P. J. Flynn and J. C. Buckner

Mayo Clinic, Rochester, MN; Mayo Clinic, Jacksonville, FL; Mayo Clinic, Rochester, MN; Metro CCOP, Minneapolis, MN

Background. Common endpoints for GBM Phase II trials are 6 mo progression-free survival (PFS6) & 12 mo OS (OS12). 
OS12 can be accurately measured, but may be confounded with subsequent therapies upon progression whereas the converse is true for PFS6. 
Our goal was to assess the relationship between these endpoints separately for Phase II trials in newly diagnosed & recurrent GBM pts. 

Methods. Data were pooled from 12 NCCTG trials for newly diagnosed GBM pts (n = 1359). 
All pts received RT and pharmaceutical therapy (pre-, during, or post-RT). 
Data were pooled from 16 recurrent GBM trials (n = 345) that used various pharmaceuticals. 
All trials were negative by design criteria. 
Overall per-pt concordance was estimated with a Kappa statistic. 
The relationship between OS12 and PFS6 across study arms was assessed by linear regression and Pearson’s correlation. 

Results. 97% (95%) of the newly diagnosed (recurrent) GBM pts, respectively, are dead. 
The OS12/PFS6 for newly diagnosed (recurrent) pts was 0.40/0.45 (0.14/0.12). 
There was only moderate concordance between the endpoints both per-pt and across study arms. 
We established Phase II efficacy criteria for each endpoint based on the pooled estimates of OS12 (PFS6). 
We simulated 1000 trials using the pooled data: 89% & 73% of the simulated newly diagnosed GBM trials were negative using the OS12 & PFS6 endpoints, respectively, and 80% & 57% of the recurrent GBM trials were negative using the OS12 & PFS6 endpoints, respectively. 

Conclusions. For newly diagnosed and recurrent GBM Phase II trials, there was only moderate concordance between PFS6 and OS12 on a per-pt and study arm basis. 
Furthermore, simulation showed OS12 predicts a negative result (truth) more often than PFS6. 
Assuming minimal survival impact of additional therapies, these results suggest OS12 is a better endpoint for GBM Phase II clinical trials in both newly diagnosed and recurrent GBM.