A nationwide genome screening project in Japan (LC-SCRUM-Japan) has been established for the development of molecular-targeted therapies for lung cancers.
Since 2013, ALK/ROS1/RET fusions have been analyzed by RT-PCR and FISH, and since 2015, multi-gene alterations have been also analyzed by a next-generation sequencing (NGS) system, Oncomine™ Comprehensive Assay. A large-scale clinico-genomic database has been developed based on the molecular screening and the monitoring of therapeutic efficacy and patient survival.
As of December, 2018, 263 institutions were participating and 5360 non-squamous non-small cell lung cancer patients had been enrolled. The success rates of RT-PCR and NGS were 94% and 91%, respectively. Of 4874 available samples, a total of 2135 targetable gene alterations (521 KRAS mut, 157 ROS1 fus, 136 MET ex14skip/amp, 131 BRAF mut, 128 ERBB2 ex20ins, 126 RET fus, 118 ALK fus, 73 EGFR ex20ins, 10 AKT1 mut, 9 NRG1 fus, 6 FGFR2/3 fus, 2 NTRK3 fus and others) were detected. Through this screening, 963 genotype-matched patients to molecular-targeted clinical trials were identified, and 172 of them (18%) were enrolled into the trials, resulting in the approval of ROS1- and BRAF-targeted therapies in Japan. Based on our database, in patients with EGFR/ERBB2 ex20ins, MET ex14skip and RET fusions, the median overall survivals were 18.5 (95%CI, 15.4-28.1), 38.0 (8.8-NR) and 51.3 (33.4-73.4) months, respectively. In these 3 subtypes, the objective response rate of 1st-line platinum-containing chemotherapies were 33%, 23% and 30%, respectively, and the progression-free survivals were 6.0 (95%CI, 5.0-7.0), 6.8 (4.4-8.4) and 10.5 (8.1-15.2) months, respectively. These historical data are valuable for evaluating efficacy of novel targeted drugs.
Our large-scale screening and clinico-genomic database contribute to the development of novel targeted therapies, especially for ROS1-, BRAF-, EGFR/ERBB2 ex20ins-, MET- and RET-positive lung cancers. In addition to the tissue-based NGS assay, NGS with liquid biopsy and multi-target qPCR assay will be started for further development of targeted drugs and companion diagnostics from 2019 in LC-SCRUM-Japan.
UMIN000010234.
National Cancer Center Japan.
Astellas Pharma, AstraZeneca, Amgen, Eisai, Ono Pharmaceutical, Kyowa Hakko Kirin, MSD, Merck Serono, Daiichi Sankyo, Taiho Pharmaceutical, Takeda Pharmaceutical, Pfizer, Novartis Pharma, Eily Lilly.
S. Matsumoto: Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Pfizer; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): MSD. K. Yoh: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self): Kirin Pharmaceuticals ; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Ono Pharmaceutical. T. Kato: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Advisory / Consultancy: Nitto Denko; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self): Roche; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical ; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Merck Sharp & Dohme; Honoraria (self): Novartis; Honoraria (self): Sumitomo Dainippon Pharma; Honoraria (self): Quintiles; Honoraria (self): Takeda; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Astellas Pharma . K. Nishino: Honoraria (self): Chugai Pharma. S. Sugawara: Honoraria (self): AstraZeneca; Honoraria (self): Chugai Pharma ; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Taiho Pharmaceutical ; Honoraria (self): Pfizer ; Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Ono Pharmaceutical; Honoraria (self): MSD K.K . Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Kyorin ; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: Celltrion; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD ; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self): Kyowa Hakko Kirin; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Ignyta. T. Seto: Honoraria (self): Astellas Pharma; Honoraria (self), Research grant / Funding (institution): AstraZeneca ; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Nippon Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self): Thermo Fisher Scientific; Research grant / Funding (institution): Bayer Yakuhin; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Kissei Pharmaceutical; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Merck Serono. N. Furuya: Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self): Lilly; Honoraria (self): Chugai Pharma; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Ono Pharmaceutical . K. Goto: Advisory / Consultancy: Otsuka; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical ; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self): Quintiles; Honoraria (self), Research grant / Funding (institution): Merck Serono; Honoraria (self), Research grant / Funding (institution): Life Technologies; Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self): AbbVie; Honoraria (self), Research grant / Funding (institution): Riken Genesis; Honoraria (self): Nippon Kayaku; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self): Otsuka; Honoraria (self): SRL Diagnostics. All other authors have declared no conflicts of interest.