- 作者：Marcel Wiesweg ; Saskia Ting ; Henning Reis ; Karl Worm ; Stefan Kasper ; Mitra Tewes ; Anja Welt ; Heike Richly ; Johannes Meiler ; Sebastian Bauer ; J?rg Hense ; Thomas C. Gauler ; Jens K?hler ; Wilfried E. Eberhardt ; Kaid Darwiche ; Lutz Freitag ; Georgios Stamatis ; Frank Breitenb¨¹cher ; Jeremias Wohlschlaeger ; Dirk Theegarten ; et al.
- 关键词：Biomarker ; Colorectal cancer ; Lung cancer ; Mutation ; Personalised medicine ; Profiling
- 刊名：European Journal of Cancer
- 出版年：2013
- 出版时间：October, 2013
- 年：2013
- 卷：49
- 期：15
- 页码：3076-3082
- 全文大小：312 K
Purpose
Multiple investigational drugs are currently explored in cancer patient populations defined by specific biomarkers. This demands a new process of patient selection for clinical trials.Patients and methods
Starting January 1, 2012, preemptive biomarker profiling was offered at the West German Cancer Center to all patients with advanced non-small-cell lung (NSCLC) or colorectal cancer (CRC), who met generic study inclusion criteria. Tumour specimens were subjected to prespecified profiling algorithms to detect ¡®actionable biomarkers¡¯ by amplicon sequencing, in situ hybridisation and immunohistochemistry. The clinical course was closely monitored to offer trial participation whenever applicable.
Results
Within 12 months, 267 patients (188 NSCLC, 79 CRC) were profiled. Estimated additional cost for biomarker profiling was 219615.51 EUR excluding histopathology workup and administration. The most prevalent biomarkers in pulmonary adenocarcinoma were KRAS mutations (29 % ), loss of PTEN expression (18 % ), EGFR mutations (9 % ), HER2 amplification (5 % ) and BRAF mutations (3 % ), while the prevalence of ALK translocations and PIK3CA mutations was extremely low. In pulmonary squamous cell carcinoma FGFR1 amplifications were found in 15 % , PTEN expression was lost in 20 % and DDR2 was mutated in a single case. KRAS mutations (41 % ) predominated in CRC, followed by loss of PTEN expression (16 % ), PIK3CA (5 % ) and BRAF (5 % ) mutations. So far 13 patients (5 % ) have entered biomarker-stratified clinical trials. Therapeutic decisions for approved drugs were guided in another 45 patients (17 % ).
Conclusion
Preemptive biomarker profiling can be implemented into the diagnostic algorithm of a large Comprehensive Cancer Center. Substantial investments in diagnostics and administration are required.