Rolfo Christian, O'Brate Aurora, Menzel Christoph, Bruns Rolf, Juraeva Dilafruz, Stroh Christopher, Johne Andreas, Paik Paul K
Center for Thoracic Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Global Medical Affairs, the healthcare business of Merck KGaA, Darmstadt, Germany.
Clin Cancer Res. 2025 Jul 1;31(13):2675-2684. doi: 10.1158/1078-0432.CCR-24-4097.
The VISION trial of tepotinib, a selective MET inhibitor, enrolled patients with non-small cell lung cancer and prospectively detected MET exon 14 (METex14) skipping in liquid biopsies (LBx) and/or tissue biopsies (TBx). We evaluated patient characteristics and outcomes according to METex14 positivity in LBx (LBx-positive) or TBx (TBx-positive).
METex14 was centrally assessed by next-generation sequencing of ctDNA from LBx (Guardant360/ArcherMET) and/or RNA from TBx (Oncomine Focus/ArcherMET) or, in Japan only, local TBx PCR. Parallel LBx/TBx testing was recommended but not mandatory. Eligibility required LBx-positive or TBx-positive status. ctDNA burden was analyzed in patients with baseline Guardant360 data.
METex14 was detected in 469 of 7,937 prescreened/screened patients, 313 of whom were enrolled (TBx-positive, n = 208; LBx-positive, n = 178). LBx-positive patients had higher radiographic tumor burden than TBx-positive patients, including higher median sum of target lesion diameters per RECIST v1.1 (67.1 vs. 55.2 mm) and more patients with ≥3 target lesions (27.5% vs. 18.8%). In 180 TBx-positive patients with matching LBx results, objective response rates were slightly higher in TBx-positive/LBx-positive patients, but TBx-positive/LBx-negative patients had longer duration of response, progression-free survival, and overall survival. In ctDNA analysis (n = 165), detectable baseline ctDNA burden was associated with shorter progression-free survival and overall survival.
Tepotinib had robust, durable activity in TBx-positive/LBx-negative and TBx-positive/LBx-positive patients. Although LBx is a complementary method to TBx for detecting METex14, it may preferentially select patients with higher tumor burden and poorer prognosis. Undetectable METex14 in baseline ctDNA (due to low ctDNA shedding) may define more favorable treatment outcomes.
tepotinib（一种选择性MET抑制剂）的VISION试验纳入了非小细胞肺癌患者，并前瞻性地在液体活检（LBx）和/或组织活检（TBx）中检测MET第14外显子（METex14）跳跃情况。我们根据LBx（LBx阳性）或TBx（TBx阳性）中的METex14阳性情况评估了患者特征和预后。
通过对LBx的ctDNA（Guardant360/ArcherMET）和/或TBx的RNA（Oncomine Focus/ArcherMET）进行下一代测序，或仅在日本通过局部TBx PCR对METex14进行中心评估。建议进行平行LBx/TBx检测，但非强制要求。入选标准为LBx阳性或TBx阳性状态。对有基线Guardant360数据的患者分析ctDNA负荷。
在7937例预筛选/筛选患者中的469例检测到METex14，其中313例入组（TBx阳性，n = 208；LBx阳性，n = 178）。LBx阳性患者的影像学肿瘤负荷高于TBx阳性患者，包括根据RECIST v1.1标准的目标病灶直径总和中位数更高（67.1对55.2 mm）以及更多有≥3个目标病灶的患者（27.5%对18.8%）。在180例TBx阳性且LBx结果匹配的患者中，TBx阳性/LBx阳性患者的客观缓解率略高，但TBx阳性/LBx阴性患者的缓解持续时间、无进展生存期和总生存期更长。在ctDNA分析（n = 165）中，可检测到的基线ctDNA负荷与较短的无进展生存期和总生存期相关。
tepotinib在TBx阳性/LBx阴性和TBx阳性/LBx阳性患者中具有强大且持久的活性。虽然LBx是检测METex14的TBx的补充方法，但它可能优先选择肿瘤负荷更高且预后更差的患者。基线ctDNA中未检测到METex14（由于ctDNA释放量低）可能预示更有利的治疗结果。
