Contribution of nationwide genome screening in Japan (LC-SCRUM-Japan) to the development of precision medicine for non-small cell lung cancer.

Abstract

9085 Background: A nationwide genome screening project in Japan (LC-SCRUM-Japan) has been established for the development of lung cancer precision medicine. Methods: Since 2013, non-squamous non-small lung cancer patients have been screened for ALK/ROS1/RET fusions using RT-PCR and FISH, and since 2015, they have also analyzed for 143 gene alterations using a next-generation sequencing (NGS) system, Oncomine™ Comprehensive Assay. Based on the molecular screening and the monitoring of clinical course and patient survival, a large-scale integrative clinico-genomic database has been established. Results: As of December, 2017, 251 institutions were participating and 4371 patients had been enrolled. The success rates of RT-PCR and NGS were 95% and 92%, respectively. Of 3919 available samples, a total of 1568 actionable gene alterations (382 KRAS mut, 193 ERBB2 mut/amp, 142 ROS1 fus, 100 RET fus, 98 MET skip/amp, 97 BRAF mut, 97 ALK fus, 96 PIK3CA mut, 54 FGFR1 amp, 13 NRAS mut, 6 AKT1 mut, 6 FGFR2/3 fus, 4 NRG1 fus, 2 NTRK3 fus and others) were detected in 1505 samples (38%). The concordance rates of the results in ALK, ROS1 and RET fusion detection between NGS and the corresponding RT-PCR were 0.98, 0.99 and 0.99, respectively. Through this screening, a total of 793 genotype-matched patients to molecular-targeted clinical trials were identified, and 136 of them (17%) were enrolled into the trials. Of the 2345 patients analyzed by NGS, the survival data were available in 1298 (55%). The patients with actionable gene alterations who were treated with targeted agents (n = 136) had significantly longer overall survivals than those not treated with targeted agents (n = 401) or the patients without actionable gene alterations (n = 761) (median survival [95%CI], 4.2 [2.4-8.2.] vs. 3.4 [2.3-5.8] vs. 2.3 [1.9-2.8] years, respectively; p = 0.01). Conclusions: LC-SCRUM-Japan contributes to the development of precision medicine, especially for ROS1, RET, ERBB2, BRAF and MET-positive lung cancers. In addition to the tissue-based molecular screening, a NGS assay with liquid biopsy was started in December 2017 and is now ongoing in the LC-SCRUM-Japan.