1276P - Genomic screening by multi-gene assay for perioperative targeted therapy in patients with early-stage non-small cell lung cancer: LC-SCRUM-Advantage/MRD

Background

Several recent clinical trials on perioperative targeted therapy for oncogene-driven early-stage non-small cell lung cancer (NSCLC) are in progress. We evaluated the feasibility of multi-gene assay by preoperative biopsy tumor samples to detect actionable oncogenic drivers in patients with operable NSCLC as in part of a multicenter prospective genomic screening study in Japan (LC-SCRUM-Advantage/MRD).

Methods

Patients with operable clinical stage I to III NSCLC were eligible for this study. Preoperative biopsy tumor samples were collected before surgery, and AmoyDx Pan Lung Cancer PCR Panel (multi-PCR panel) was performed for a measurement of oncogenic drivers including EGFR, ALK, ROS1, KRAS, BRAF, HER2, RET, MET and NTRK genes. Surgical tumor samples were also collected after surgery, and used for analysis for 50 gene alterations using a next-generation sequencing system, Oncomine Precision Assay (OPA).

Results

Between August 2022 and April 2023, a total of 193 patients were enrolled in LC-SCRUM-Advantage/MRD. Of 77 evaluable patients at this analysis, 40 (52%) had stage I, 23 (30%) had stage II, 14 (18%) had stage III disease and 57 (74%) had adenocarcinoma histology. Success rate of multi-PCR panel by preoperative samples was 96%, and median turnaround time (TAT) was 4 days (range, 3-8). The frequencies of detected oncogenic drivers were 29 (39%) EGFR mutations (16, L858R; 10, ex19del; 3, uncommon), 9 (12%) KRAS (4, G12C; 5, nonG12C), 2 (3%) HER2 ex20ins and 1 (2%) RET fusion. Among patients who completed surgery and OPA by surgical samples, success rate of OPA was 98%, and median TAT was 6 days (range, 3-12). Concordance rate of detected actionable oncogenic drivers between preoperative biopsy and surgical samples was 98% (49/50), and one patient with KRAS G12D was detected only in OPA by surgical sample.

Conclusions

Multi-PCR panel showed a high success rate and a short TAT in genomic screening by preoperative biopsy tumor samples. Multi-PCR panel would help to better detect actionable oncogenic drivers in patients with early-stage NSCLC.

Clinical trial identification

UMIN000048977.

Editorial acknowledgement

Legal entity responsible for the study

LC-SCRUM.

Funding

National Cancer Center Hospital East.

Disclosure

K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Lilly, Boehringer Ingelheim, Amgen, Takeda, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Lilly, Daiichi Sankyo, AbbVie, Taiho, MSD, Takeda, Amgen, Boehringer Ingelheim, Chugai. Y. Zenke: Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly, Chugai, Boehringer Ingelheim, Ono Pharmaceutical, Bristol Myers Squibb, Takeda Pharmaceutical, Taiho Pharmaceutical, MSD, Novartis, Nippon-Kayaku, Amgen, Kyowa-Hakko Kirin; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, MSD, Merck, Daiichi Sankyo, Amgen. J. Samejima: Financial Interests, Personal, Writing Engagement: Taiho Pharmaceutical Co., Ltd, Shizenkagakusha, Stryker, Ziosoft; Financial Interests, Personal, Invited Speaker: B Braun, Ziosoft, Johnson & Johnson, MiRXES, Taiho Pharmaceutical Co., Ltd; Financial Interests, Personal, Other, Providing surgical videos: Olympus, Johnson & Johnson. H. Daga: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical, AstraZeneca. K. Kunimasa: Financial Interests, Institutional, Local PI: Taiho, AbbVie; Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Nippon Boehringer Ingelheim, Eli Lilly Japan, Roche Diagnostics, Daiichi Sankyo, Novartis, Pfizer, Merk, Bristol Myers Squibb, Nippon Kayaku. I. Nakachi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Novartis Pharma. A. Osoegawa: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, AstraZeneca, MSD, Ono, Chugai. H. Izumi: Financial Interests, Institutional, Local PI: Amgen Inc, Eisai, AbbVie; Financial Interests, Personal and Institutional, Local PI, Invited Speaker: Ono Pharmaceutical Company, AstraZeneca; Financial Interests, Personal, Other, Invited Speaker: Chugai Pharmaceutical Co., Merck Biopharma Co., Takeda Pharmaceutical Co.; Financial Interests, Personal, Other, Advisory board: Amgen. T. Sakai: Financial Interests, Institutional, Local PI: Amgen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Thermo Fisher Scientific, Chugai, MSD, Merck. S. Umemura: Financial Interests, Personal, Invited Speaker: Chugai. S. Matsumoto: Financial Interests, Personal, Invited Speaker: Merck Biopharma, Eli Lilly, AstraZeneca, Chugai, Novartis, Guardant Health, Amgen, Takeda; Financial Interests, Institutional, Local PI: Merck Biopharma, Janssen Pharmaceutical K.K., MSD. M. Tsuboi: Financial Interests, Personal, Invited Speaker, Lecture: Johnson & Johnson Japan; Financial Interests, Personal, Advisory Board, Lectures, Advisory boards: AstraZeneca KK, Chugai Pharmaceutical Co.,Ltd, MSD; Financial Interests, Personal, Invited Speaker, Lectures: Eli Lilly Japan, Bristol Myers Squibb KK, Taiho Pharma, Medtronic Japan, Ono Pharmaceutical Co., Ltd; Financial Interests, Personal, Advisory Board, Advisory boards: Novartis; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo company limited; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical Co., Ltd, Bristol Myers Squibb KK, Novartis, MiRXES; Financial Interests, Personal, Steering Committee Member: MSD, AstraZeneca, Novartis; Financial Interests, Institutional, Steering Committee Member: Eli Lilly Japan. K. Goto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Amoy Diagnosties Co.,Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Guardant Health Inc., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K., Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K.; Financial Interests, Personal, Expert Testimony: Medpace Japan K.K.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Ignyta,Inc., Janssen Pharmaceutical K.K., Kissei Pharmaceutical Co., Ltd., Loxo Oncology, Inc., Medical & Biological Laboratories Co., Ltd., Merck Biopharma Co., Ltd., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics, Inc., Amgen Astellas BioPharma K.K., Bayer Yakuhin, Ltd., Blueprint Medicines Corporation., Life Technologies Japan Ltd., NEC Corporation., Novartis Pharma K.K.; Non-Financial Interests, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. All other authors have declared no conflicts of interest.