A few years ago, I reviewed a blood test called VeriStrat that evaluates the patterns of proteins in the blood and reports a profile of either “Good” (in about 2/3 of patients with advanced NSCLC) or “Poor” (in the remaining 1/3 of patients) for EGFR inhibitor therapy. This was predictive of whether a patient would have a more favorable or potentially less favorable survival with an EGFR tyrosine kinase inhibitor like Iressa (gefitinib) or Tarceva (erlotinib) compared with placebo.   My leading issues with the test were that:

1) Testing as “Good” doesn’t mean that a patient will do well because of the EGFR inhibitor. A few of patients who tested as “Good” progressed right through Tarceva, though they still did well overall.  So while they might have had a favorable survival, in some cases it was because of the beneficial effect   of chemo or a slowly progressing cancer, not the EGFR inhibitor.

2)   The focus of the VeriStrat test has been to ask the question “Should I pursue an EGFR inhibitor at all?”.  While that is a valid question, it’s one that many patients are not eager to ask, at least not US-based patients.  With Tarceva otherwise being an FDA approved and very appropriate treatment for previously treated patients with advanced NSCLC, most of my patients aren’t looking for a test that will remove a treatment option that is on a short list of treatments with proven benefit for previously treated advanced NSCLC.

But some new data presented by Dr. Tom Stinchecombe from the University of North Carolina at Chapel Hill (where Dr. Weiss also works) illustrates the use of the VeriStrat test to ask a different question: “Am I better served by receiving Tarceva or standard chemo for my advanced NSCLC?”.   The trial was specifically for patients age 70 or older with previously untreated advanced NSCLC, randomizing 146 patients to either gemcitabine chemotherapy as a single agent, Tarceva alone, or a combination of gemcitabine and Tarceva concurrently (with the latter at a dose of 100 mg per day). From that group, 124 serum samples were sent for testing, with results obtained from 110, and results were matched with clinical data in 98.  As in prior studies of the VeriStrat platform, the breakdown was “Good” for 2/3, “Poor” for 1/3.

For the gemcitabine alone arm, progression-free survival (PFS) and overall survival (OS) were the same regardless of VeriStrat test result.  In contrast, results in the two VeriStrat groups were very different for the patients who received Tarceva as a single agent, while the combination arm showed differences that were in between chemo alone and Tarceva alone:.

Multivariate analysis revealed that VeriStrat status was among the most predictive variables of patient outcome for both PFS and OS.

These results have significant limitations: the trial is not large, only a subset of patients have matched serum samples and clinical results, and the treatments assigned are not standard for first-line advanced NSCLC.   Nevertheless, they are provocative and speak to a question that I think is more relevant in my practice than “Should I even try an EGFR inhibitor?”, and that is “Am I better served with chemo or an EGFR inhibitor?”.

These results don’t answer the question definitively, even if they do lead me to want to be especially wary about ever prioritizing Tarceva over chemo if I knew a patient was in the VeriStrat Poor group.   But the more definitive answer will come from the PROSE study, in which 275 patients with previously treated advanced NSCLC who undergo VeriStrat testing and get a clear result back are then randomized to chemo or Tarceva.  The results from this study, which are expected in time for the next ASCO meeting, in early June, 2013, will lead me to be far more inclined to order the VeriStrat test for my own patients if it demonstrates that it can distinguish which (presumably EGFR mutation negative) patients with advanced NSCLC should receive chemo vs. Tarceva. 

What do you think? Would you want VeriStrat testing as an answer to the question of “Should I not take an EGFR inhibitor at all?”, and if you came back as “VeriStrat Poor status”, do you think you wouldn’t want to try an EGFR inhibitor?  Would the test be appealing before initiating second line treatment?