Meeting
2014 ASCO Annual Meeting
Multiplex genomic profiling of non-small cell lung cancer patients enrolled in the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin (WJOG6611LTR).
Authors
Hiroshige Yoshioka
Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan
Hiroshige Yoshioka , Isamu Okamoto , Kazuko Sakai , Satoshi Morita , Hiroyasu Kaneda , Koji Takeda , Tomonori Hirashima , Yoshihito Kogure , Tatsuo Kimura , Toshiaki Takahashi , Shinji Atagi , Takashi Seto , Toshiyuki Sawa , Masashi Yamamoto , Miyako Satouchi , Motoyasu Okuno , Seisuke Nagase , Kazuhiko Nakagawa , Yoichi Nakanishi , Kazuto Nishio
Organizations
Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan, Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan, Department of Genome Biology, Kinki University School of Medicine, Osaka, Japan, Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan, Department of Medical Oncology, Kinki University, Osaka, Japan, Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan, Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan, Department of Respiratory Medicine, Nagoya Medical Center, Nagoya, Japan, Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan, Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Japan, Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan, Gifu Municipal Hospital, Gifu, Japan, Nagoya Ekisaikai Hospital, Nagoya, Japan, Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan, Aichi Cancer Center Aichi Hospital, Okazaki, Japan, Tokyo Medical University, Tokyo, Japan, Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan, Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, Department of Genome Biology, Kinki University Faculty of Medicine, Osaka, Japan
Research Funding
No funding sources reported
Background: High-throughput genotyping tests to evaluate large numbers of genetic abnormalities in non–small cell lung cancer (NSCLC) are needed. Methods: Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from patients with advanced NSCLC enrolled in the LETS phase III trial. With the use of the multiplex platform of Sequenom’s MassARRAY assays, we performed high-throughput genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel). We also evaluated MET amplification by fluorescence in situ hybridization. Results: The numbers of evaluable patients were 275 for somatic gene mutations, 240 for fusion genes, and 229 for MET amplification. A somatic mutation in at least one gene was identified in 105 (48%) of the 217 patients with nonsquamous cell carcinoma (non-SCC) and in 26 (45%) of the 58 patients with SCC. Overall, we identified EGFR mutations in 46 patients (17%), TP53 mutations in 30 (11%), STK11 mutations in 27 (9.8%), MET mutations in 21 (7.6%), KRAS mutations in 17 (6.2%), PIK3CA mutations in 6 (2.2%), and BRAF and NRAS mutations in 3 each (1.1%). Median overall survival of EGFR mutation–positive patients was significantly longer than that of those without EGFR mutations (23.7 vs. 12.6 months, P = 0.004). Conversely, patients with KRAS mutations had a significantly shorter survival time than did those with wild-type KRAS (9.9 vs. 15.3 months, P = 0.04). ALK fusions were detected in six cases (2.5%), ROS1 fusions in five (2.1%), and RET fusions in one (0.4%), with these three types of rearrangement being mutually exclusive. Median overall survival was 19.5 versus 13.8 months for fusion gene–positive and –negative patients, respectively (P = 0.89). De novo MET amplification was identified in 9 patients (3.9%). Conclusions: This first multiplex genotyping of NSCLC accompanying a phase III study demonstrates that MassARRAY-based testing performs well with nucleic acid derived from FFPE tissue obtained from patients with advanced NSCLC.
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Abstract Details
Session Type
Poster Session
Session Title
Lung Cancer - Non-Small Cell Metastatic
Track
Lung Cancer
Sub Track
Metastatic Non–Small Cell Lung Cancer
Citation
J Clin Oncol 32:5s, 2014 (suppl; abstr 8095)
DOI
10.1200/jco.2014.32.15_suppl.8095
Abstract #
8095
Poster Bd #
276
Abstract Disclosures
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