PO.CL12.02 · 临床研究

Clinical, genomic, and therapeutic outcomes of lung squamous cell carcinoma with high LGR5 expression : A study from the LC-SCRUM-Asia database

编号 7919 展板 24 时间 4/22 09:00–12:00 区域 Section 48 主讲 Yu Tanaka, MD;PhD

分会场 Translational Biomarkers and Emerging Molecular Approaches

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作者与单位

Yu Tanaka¹, Shuji Murakami², Kazumi Nishino³, Motoko Tachihara⁴, Ichiro Nakachi⁵, Mayu Kawakami⁶, Satoshi Hara⁷, hitomi Aono⁸, Shoichi Kuyama⁹, Gaku Yamamoto¹, Eri Sugiyama¹, Tetsuya Sakai¹, Hiroki Izumi¹, Shigeki Umemura¹, HIBIKI UDAGAWA¹, Yoshitaka Zenke¹, Shingo Matsumoto¹, Kiyotaka Yoh¹, Koichi Goto¹

¹National Cancer Center Hospital East, Chiba, Japan,²Kanagawa Cancer Center, Kanagawa, Japan,³Osaka International Cancer Institute, Osaka, Japan,⁴Kobe University Hospital, Hyogo, Japan,⁵Research Scholar, Dept. of Medicine, University of Colorado Denver, Aurora, CO,⁶Saiseikai Imabari Hospital, Ehime, Japan,⁷Itami City Hospital, Osaka, Japan,⁸Tokyo Metropolitan Police Hospital, Tokyo, Japan,⁹National Hospital Organization Iwakuni Clinical Center, Yamaguchi, Japan

摘要 Abstract

Introduction: Petosemtamab, a bispecific antibody targeting LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) and EGFR, is under clinical development. Wnt-driven LGR5, a stem cell-associated marker, stabilizes EGFR by preventing lysosomal degradation, thereby promoting cancer cell survival. However, its role in lung squamous cell carcinoma (LUSC) remains unclear. This study evaluates the impact of LGR5 expression on clinical characteristics, genomic alterations, and therapeutic outcomes in LUSC. Methods: Using the LC-SCRUM-Asia clinico-genomic database, mRNA levels of LGR5 , EGFR , and other genes were assessed via the AMOY Master Panel. High LGR5 was defined as above the median. Clinical, genomic characteristics, and treatment outcomes were compared between high and low LGR5 groups. Results: LGR5 expression was evaluated in 233 LUSC patients between June 2021 and February 2022. The median LGR5 expression was 0.02 FPKM (range: 0.00-5.44), and the median EGFR expression was 12.09 FPKM (range: 0.07-572.49). No correlation was observed between LGR5 and EGFR expression (Pearson r = -0.0387, P = 0.687). Clinical characteristics, including age, sex, smoking history, ECOG-PS, and clinical stage, did not differ significantly between high and low LGR5 groups. The prevalence of driver gene alterations ( KRAS mutation: 6 vs. 3, EGFR mutation: 2 vs. 4, MET ex14 skipping: 2 vs. 4, ALK fusion: 3 vs. 1) also showed no significant differences ( P = 0.816). Among 103 patients receiving first-line ICI with or without chemotherapy, the median PFS was 8.0 months in the high LGR5 group and 5.6 months in the low LGR5 group (HR = 0.91, 95% CI: 0.58-1.44, P = 0.570). In 90 patients treated with first-line platinum-based chemotherapy, the median PFS was 5.5 months in the high LGR5 group and 4.3 months in the low LGR5 group (HR = 0.99, 95% CI: 0.52-1.91, P = 0.985). Wnt ( P -weighted Log2FC = 0.753), Hedgehog ( P -weighted Log2FC = 0.877), and Notch ( P -weighted Log2FC = 0.564) pathways, key regulators of stem cell function, were significantly upregulated in the high LGR5 group (all P < 0.05). Conclusion: High LGR5 expression does not define a clinically or genomically distinct subgroup of LUSC; however, it is associated with a transcriptionally stemness-activated phenotype characterized by upregulation of Wnt, Hedgehog, and Notch pathways. These findings suggest that LGR5-high LUSC represents a biologically distinct subtype that may inform future development of LGR5×EGFR-targeted therapies.

利益披露 Disclosure

Y. Tanaka, CHUGAI PHARMACEUTICAL CO., LTD. ). MSD ). Eli Lilly and Company ). AstraZeneca ). Taiho ). S. Murakami, None. K. Nishino, ONO ). TAIHO ). MSD ). AbbVie ). Daiichi-Sankyo ). Amgen ). Eisai ). Sanofir ). Janssen ). Novartis ). Pfizer ). Eli Lilly ). Merck Biopharma ). Takeda ). AstraZeneca ). Merus NV ). Gilead ). Chugai ). Bayer ). M. Tachihara, AstraZeneca ). Chugai Pharmaceutical ). Eli Lilly Japan Co Ltd ). Ono Pharmaceutical Co Ltd ). Bristol-Myers Squibb Co Ltd ). Chugai Pharmaceutical Co Ltd ). MSD KK ). Novartis pharmaceuticals K.K ). Takeda Pharmaceutical Co., Ltd. ). Taiho Pharmaceutical Co., Ltd. ). Nippon Boehringer Ingelheim Co.,Ltd. ). Daiichi Sankyo ). Pfizer Japan Inc. ). Janssen Pharmaceutical K.K. ). M. Kawakami, None.. S. Hara, None.. H. Aono, None.. S. Kuyama, None. G. Yamamoto, Astra Zeneca Independent Contractor. E. Sugiyama, None. T. Sakai, Amgen ). GSK ). Daiichi-Sankyo ). NEC ). H. Izumi, Amgen ). Eisai Co., Ltd. ). Takeda ). Bristol‑Myers Squibb Japan ). Chugai ). AstraZeneca K.K. ). Ono Pharmaceutical Co., Ltd. ). MSD ). Merck ). S. Umemura, Taiho Pharmaceutical ). Lilly ). MSD ). H. Udagawa, Takeda Pharmaceutical Co., Ltd ). Nippon Boehringer Ingelheim Co., Ltd ). Amgen K.K. ). Taiho Pharmaceutical Co., Ltd. ). MSD K.K ). DAIICHI SANKYO COMPANY, LIMITED ). CHUGAI PHARMACEUTICAL CO., LTD ). Y. Zenke, AstraZeneca ). Daiichi-Sankyo ). Amgen ). GSK, Roche ). MSD ). Merck ). S. Matsumoto, Merck KGaA Independent Contractor. Chugai Pharmaceutical Co., Ltd. Independent Contractor. MSD ). K. Yoh, AbbVie ). Amgen ). ArriVent Biopharma ). AstraZeneca ). Boehringer Ingelheim ). Chugai ). Daiichi-Sankyo ). Lilly ). MSD ). Taiho ). Takeda ). K. Goto, Merus NV ). Astellas Pharma ). AstraZeneca K.K. ). Nippon Boehringer Ingelheim ). Bristol-Myers Squibb K.K. ). Chugai ). Daiichi-Sankyo ). Eisai, Janssen. ). Kyowa Kirin ). Merck Biopharma ). MBL ). MSD K.K. ). Novartis ). ONO ). Pfizer R&D Japan ). Sumitomo Pharma ). Taiho ). Eli Lilly Japan ). Bayer Yakuhin ). Takeda. ).

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