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.
PURPOSE: Multiple investigational drugs are currently explored in cancerpatient 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 carcinomaFGFR1 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.
Authors: C Lim; H S Sekhon; J C Cutz; D M Hwang; S Kamel-Reid; R F Carter; G da Cunha Santos; T Waddell; M Binnie; M Patel; N Paul; T Chung; A Brade; R El-Maraghi; C Sit; M S Tsao; N B Leighl Journal: Curr Oncol Date: 2017-04-27 Impact factor: 3.677
Authors: Lynette M Sholl; Dara L Aisner; Marileila Varella-Garcia; Lynne D Berry; Dora Dias-Santagata; Ignacio I Wistuba; Heidi Chen; Junya Fujimoto; Kelly Kugler; Wilbur A Franklin; A John Iafrate; Marc Ladanyi; Mark G Kris; Bruce E Johnson; Paul A Bunn; John D Minna; David J Kwiatkowski Journal: J Thorac Oncol Date: 2015-05 Impact factor: 15.609
Authors: Julian C Schink; Julia R Trosman; Christine B Weldon; Kalliopi P Siziopikou; Gregory J Tsongalis; Alfred W Rademaker; Jyoti D Patel; Al B Benson; Edith A Perez; William J Gradishar Journal: J Natl Cancer Inst Date: 2014-09-12 Impact factor: 13.506
Authors: S Q Wong; A Fellowes; K Doig; J Ellul; T J Bosma; D Irwin; R Vedururu; A Y-C Tan; J Weiss; K S Chan; M Lucas; D M Thomas; A Dobrovic; J P Parisot; S B Fox Journal: Br J Cancer Date: 2015-03-05 Impact factor: 7.640
Authors: F Oezkan; Am Khan; P Zarogoulidis; W Hohenforst-Schmidt; D Theegarten; K Yasufuku; T Nakajima; L Freitag; K Darwiche Journal: Onco Targets Ther Date: 2014-11-10 Impact factor: 4.147
Authors: Stefan Kasper; Henning Reis; Sophie Ziegler; Silke Nothdurft; Andre Mueller; Moritz Goetz; Marcel Wiesweg; Jeannette Phasue; Saskia Ting; Sarah Wieczorek; Anna Even; Karl Worm; Michael Pogorzelski; Sandra Breitenbuecher; Johannes Meiler; Andreas Paul; Tanja Trarbach; Kurt Werner Schmid; Frank Breitenbuecher; Martin Schuler Journal: Oncotarget Date: 2017-07-11