PMID- 23172885
OWN - NLM
STAT- MEDLINE
DCOM- 20130703
LR  - 20130118
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 19
IP  - 2
DP  - 2013 Jan 15
TI  - Tumor burden modeling versus progression-free survival for phase II decision 
      making.
PG  - 314-9
LID - 10.1158/1078-0432.CCR-12-2161 [doi]
AB  - Randomized Phase II oncology trial endpoints for decision making include both 
      progression-free survival (PFS) and change in tumor burden as measured by the sum 
      of longest diameters (SLD) of the target lesions. In addition to observed SLD 
      changes, tumor shrinkage and growth parameters can be estimated from the 
      patient-specific SLD profile over time. The ability of these SLD analyses to 
      identify an active drug is contrasted with that of a PFS analysis through the 
      simulation of Phase II trials via resampling from each of 6 large, Phase II and 
      III trials, 5 of which were positive and one negative. From each simulated Phase 
      II trial, a P value was obtained from 4 analyses-a log-rank test on PFS, a 
      Wilcoxon rank-sum test on the minimum observed percentage change from baseline in 
      SLD, and 2 nonlinear, mixed-effects model analyses of the SLD profiles. All 4 
      analyses led to approximately uniformly distributed P values in the negative 
      trial. The PFS analysis was the best or nearly the best analysis in the other 5 
      trials. In only one of the positive studies did the modeling analysis outperform 
      the analysis of the minimum SLD. In conclusion, for the decision to start a Phase 
      III trial based on the results of a randomized Phase II trial of an oncology 
      drug, PFS appears to be a better endpoint than does SLD, whether analyzed through 
      simple SLD endpoints, such as the minimum percentage change from baseline, or 
      through the modeling of the SLD time course to estimate tumor dynamics.
CI  - (c)2012 AACR.
FAU - Kaiser, Lee D
AU  - Kaiser LD
AD  - Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. lkaiser@gene.com
LA  - eng
PT  - Journal Article
DEP - 20121121
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
SB  - IM
MH  - Clinical Trials, Phase II as Topic
MH  - Computer Simulation
MH  - Disease-Free Survival
MH  - Humans
MH  - *Models, Statistical
MH  - Neoplasms/*mortality/*pathology/therapy
MH  - Randomized Controlled Trials as Topic
MH  - *Tumor Burden
EDAT- 2012/11/23 06:00
MHDA- 2013/07/05 06:00
CRDT- 2012/11/23 06:00
PHST- 2012/11/23 06:00 [entrez]
PHST- 2012/11/23 06:00 [pubmed]
PHST- 2013/07/05 06:00 [medline]
AID - 1078-0432.CCR-12-2161 [pii]
AID - 10.1158/1078-0432.CCR-12-2161 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2013 Jan 15;19(2):314-9. doi: 10.1158/1078-0432.CCR-12-2161. 
      Epub 2012 Nov 21.