VeriStrat classifier for survival and time to progression in non-small cell lung cancer (NSCLC) patients treated with erlotinib and bevacizumab

David P Carbone, J Stuart Salmon, Dean Billheimer, Heidi Chen, Alan Sandler, Heinrich Roder, Joanna Roder, Maxim Tsypin, Roy S Herbst, Anne S Tsao, Hai T Tran, Thao P Dang, David P Carbone, J Stuart Salmon, Dean Billheimer, Heidi Chen, Alan Sandler, Heinrich Roder, Joanna Roder, Maxim Tsypin, Roy S Herbst, Anne S Tsao, Hai T Tran, Thao P Dang

Abstract

We applied an established and commercially available serum proteomic classifier for survival after treatment with erlotinib (VeriStrat) in a blinded manner to pretreatment sera obtained from recurrent advanced NSCLC patients before treatment with the combination of erlotinib plus bevacizumab. We found that VeriStrat could classify these patients into two groups with significantly better or worse outcomes and may enable rational selection of patients more likely to benefit from this costly and potentially toxic regimen.

Conflict of interest statement

Conflict of interest statement: David Carbone is an unpaid advisor to BioDesix, but holds no patents or ownership interest with them.

Heinrich Roder, Joanna Roder, and Maxim Tsypin are Biodesix employees who performed the proteomic classification.

Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1
Figure 1
(A) Representative spectra from a patient classified as “good” (upper panel) versus another patient who was classified as “poor”. A peak around 6000 Da and another cluster of peaks in the 11000 to 12000 Da range are observed in the spectrum from a patient who was classified as “poor”. (B) A heatmap is used to visually summarize peak intensities of the eight peaks in the VeriStrat algorithm from the cohort treated with bevacizumab and erlotinib. Differences can be observed between the patients who were classified as “poor” and those who were classified as “good”.
Figure 2
Figure 2
Kaplan-Meier analysis is used to plot survival curves of patients treated with both bevacizumab and erlotinib according to “good” or “poor” classification. There was a statistically significant difference in progression-free survival and overall survival as determined by the log-rank test.

References

    1. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabarbara P, Seymour L. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005;353:123–132.
    1. Herbst RS, Onn A, Sandler A. Angiogenesis and lung cancer: prognostic and therapeutic implications. J Clin Oncol. 2005;23:3243–3256.
    1. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542–2550.
    1. Herbst RS, O'Neill VJ, Fehrenbacher L, Belani CP, Bonomi PD, Hart L, Melnyk O, Ramies D, Lin M, Sandler A. Phase II study of efficacy and safety of bevacizumab in combination with chemotherapy or erlotinib compared with chemotherapy alone for treatment of recurrent or refractory non small-cell lung cancer. J Clin Oncol. 2007;25:4743–4750.
    1. Douillard JY, Laporte S, Fossella F, Georgoulias V, Pujol JL, Kubota K, Monnier A, Kudoh S, Rubio JE, Cucherat M. Comparison of docetaxel- and vinca alkaloid-based chemotherapy in the first-line treatment of advanced non-small cell lung cancer: a meta-analysis of seven randomized clinical trials. J Thorac Oncol. 2007;2:939–946.
    1. Stinchcombe TE, Socinski MA. Bevacizumab in the treatment of non-small-cell lung cancer. Oncogene. 2007;26:3691–3698.
    1. Dowlati A, Gray R, Sandler AB, Schiller JH, Johnson DH. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab--an Eastern Cooperative Oncology Group Study. Clin Cancer Res. 2008;14:1407–1412.
    1. Taguchi F, Solomon B, Gregorc V, Roder H, Gray R, Kasahara K, Nishio M, Brahmer J, Spreafico A, Ludovini V, Massion PP, Dziadziuszko R, Schiller J, Grigorieva J, Tsypin M, Hunsucker SW, Caprioli R, Duncan MW, Hirsch FR, Bunn PA, Jr, Carbone DP. Mass spectrometry to classify non-small-cell lung cancer patients for clinical outcome after treatment with epidermal growth factor receptor tyrosine kinase inhibitors: a multicohort cross-institutional study. J Natl Cancer Inst. 2007;99:838–846.
    1. Herbst RS, Johnson DH, Mininberg E, Carbone DP, Henderson T, Kim ES, Blumenschein G, Jr, Lee JJ, Liu DD, Truong MT, Hong WK, Tran H, Tsao A, Xie D, Ramies DA, Mass R, Seshagiri S, Eberhard DA, Kelley SK, Sandler A. Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J Clin Oncol. 2005;23:2544–2555.
    1. Salmon S, Chen H, Chen S, Herbst R, Tsao A, Tran H, Sandler A, Billheimer D, Shyr Y, Lee JW, Massion P, Brahmer J, Schiller J, Carbone D, Dang TP. Classification by mass spectrometry can accurately and reliably predict outcome in patients with non-small cell lung cancer treated with erlotinib-containing regimen. J Thorac Oncol. 2009;4:689–696.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다