The NEXT-1 (Next generation pErsonalized tX with mulTi-omics and preclinical model) trial: prospective molecular screening trial of metastatic solid cancer patients, a feasibility analysis

// Seung Tae Kim 1, * , Jeeyun Lee 1, * , Mineui Hong 2, 3, * , Kyunghee Park 4, 5, * , Joon Oh Park 1 , Tae Jin Ahn 3, 4 , Se Hoon Park 1 , Young Suk Park 1 , Ho Yeong Lim 1 , Jong-Mu Sun 1 , Jin Seok Ahn 1 , Myung-Ju Ahn 1 , Hee Cheol Kim 6 , Tae Sung Sohn 6 , Dong Il Choi 7 , Jong Ho Cho 8 , Jin Seok Heo 6 , Wooil Kwon 6 , Sang Won Uhm 9 , Hyuk Lee 10 , Byung-Hoon Min 10 , Sung No Hong 10 , Duk Hwan Kim 5, 11 , Sin Ho Jung 12 , Woongyang Park 4, 5 , Kyoung-Mee Kim 2, 3 , Won Ki Kang 1 , Keunchil Park 1, 2 1 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Innovative Cancer Medicine Institute, Samsung Cancer Center, Samsung Medical Center, Seoul, Korea 3 Department of Pathology & Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 4 Samsung Genome Institute, Seoul, Korea 5 Samsung Biological Research Institute, Seoul, Korea 6 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 7 Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 8 Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 9 Division of Pulmonology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 10 Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 11 Medical Translational Research Center, Samsung Biological Research Institute, Seoul, Korea 12 Biostatistics and Clinical Epidemiology, Samsung Medical Center, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Won Ki Kang, e-mail: wkkang@skku.edu Kyoung-Mee Kim, e-mail: kkmkys@skku.edu Keunchil Park, e-mail: kpark@skku.edu Keywords: molecular profiling, genome, ampliseq Received: July 01, 2015      Accepted: August 27, 2015      Published: September 09, 2015 ABSTRACT We conducted a prospective genomic screening trial with high throughput sequencing and copy number variation (CNV) assay, and immunohistochemistry array in metastatic solid cancer patients. We used Ion AmpliSeq Cancer Hotspot Panel v2 and nCounter Copy Number Variation Assay (21 genes) to identify molecular targets for potential matched therapy. Metastatic solid tumor patients were prospectively consented for molecular profiling tests. The primary outcome for this trial was the feasibility of molecular tests and response rate (matched vs non-matched treatment). Between November 2013 and August 2014, a total of 428 metastatic solid tumor patients were enrolled on to this study. The mutational profiles were obtained for 407 (95.1%) patients. CNV 21-gene assays were successfully performed in 281 (65.7%) of 428 patients. Of the 407 patients with molecular profiling results, 342 (84.0%) patients had one or more aberrations detected. Of the 342 patients, 103 patients were matched to molecularly targeted agents in the context of clinical trials or clinical practice. The response rate was significantly higher in the genome-matched treated group for gastrointestinal/hepatobiliary/rare tumors (matched vs non-matched treatment, 42.6% vs 24.3%, P = .009) and lung cancer cohort (matched vs non-matched treatment, 61.2% vs 28.6% < P = .001) when compared with the non-matched group. In this trial, we demonstrate that genome-matched treatment based on molecular profiling result in better treatment outcome in terms of response rate.