Prognostic and predictive role of the VeriStrat plasma test in patients with advanced non-small-cell lung cancer treated with erlotinib or placebo in the NCIC Clinical Trials Group BR.21 trial.
BACKGROUND
We investigated the predictive and prognostic effects of VeriStrat, a serum or plasma-based assay, on response and survival in a subset of patients enrolled on the NCIC Clinical Trials Group, BR.21 phase III trial of erlotinib versus placebo in previously treated advanced non-small-cell lung cancer patients.


METHODS
Pretreatment plasma samples were available for 441 of 731 enrolled patients and were provided as anonymized aliquots to Biodesix. The VeriStrat test was performed in a Clinical Laboratory Improvement Act-accredited laboratory at Biodesix, Inc. (Boulder, CO). The results (Good, Poor) were returned to NCIC Clinical Trials Group, which performed all the statistical analyses.


RESULTS
VeriStrat testing was successful in 436 samples (98.9%), with 61% classified as Good. VeriStrat was prognostic for overall survival in both erlotinib-treated patients and those on placebo, independent of clinical covariates. For VeriStrat Good patients, the median survival was 10.5 months on erlotinib versus 6.6 months for placebo (hazard ratio 0.63, 95% confidence interval 0.47-0.85, p = 0.002). For VeriStrat Poor patients, the median survival was 4 months for patients receiving erlotinib, and 3.1 months for placebo (hazard ratio: 0.77, 95% confidence interval 0.55-1.06, p = 0.11). VeriStrat was predictive for objective response (p = 0.002), but was not able to predict for differential survival benefit from erlotinib (interaction p = 0.48). Similar results were found for progression-free survival.


CONCLUSIONS
We were able to confirm that VeriStrat is predictive of objective response to erlotinib. VeriStrat is prognostic for both OS and progression-free survival, independent of clinical features, but is not predictive of differential survival benefit versus placebo.
Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. carbone@osumc.edu
David P
DP
Carbone
Keyue
K
Ding
Heinrich
H
Roder
Julia
J
Grigorieva
Joanna
J
Roder
Ming-Sound
MS
Tsao
Lesley
L
Seymour
Frances A
FA
Shepherd
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015996:Survival Rate
D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors