Feasibility of preemptive biomarker profiling for personalised early clinical drug development at a Comprehensive Cancer Center

• Published in: European journal of cancer (1990) Vol. 49; no. 15; pp. 3076 - 3082
• Main Authors: Wiesweg, Marcel, Ting, Saskia, Reis, Henning, Worm, Karl, Kasper, Stefan, Tewes, Mitra, Welt, Anja, Richly, Heike, Meiler, Johannes, Bauer, Sebastian, Hense, Jörg, Gauler, Thomas C, Köhler, Jens, Eberhardt, Wilfried E, Darwiche, Kaid, Freitag, Lutz, Stamatis, Georgios, Breitenbücher, Frank, Wohlschlaeger, Jeremias, Theegarten, Dirk, Derks, Cordula, Cortes-Incio, Diana, Linden, Gabriele, Skottky, Silke, Lütkes, Peter, Dechêne, Alexander, Paul, Andreas, Markus, Peter, Schmid, Kurt W, Schuler, Martin
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.10.2013; Elsevier
• Subjects: Biological and medical sciences; Biomarker; Biomarkers, Tumor - analysis; Carcinoma, Non-Small-Cell Lung - chemistry; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Colorectal cancer; Colorectal Neoplasms - chemistry; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Drug Discovery; Feasibility Studies; Female; Hematology, Oncology and Palliative Medicine; Humans; Lung cancer; Lung Neoplasms - chemistry; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Personalised medicine; Pharmacology. Drug treatments; Precision Medicine - methods; Profiling; Prognosis; Prospective Studies; Tumors; Biomarker; Personalised medicine; Profiling; Mutation; Lung cancer; Colorectal cancer; Drug; Lung disease; Rectal disease; Respiratory disease; Biological marker; Malignant tumor; Colonic disease; Medicine; Prevention; Cancerology; Digestive diseases; Intestinal disease; Bronchus disease; Genetics; Early; Feasibility; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2013.06.014

Abstract 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.