Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice

被引：75

作者：

Le, Xiuning ^{[1
]}

Sakai, Hiroshi ^{[2
]}

Felip, Enriqueta ^{[3
]}

Veillon, Remi ^{[4
]}

Garassino, Marina Chiara ^{[5
,6
]}

Raskin, Jo ^{[7
]}

Cortot, Alexis B. ^{[8
]}

Viteri, Santiago ^{[9
]}

Mazieres, Julien ^{[10
]}

Smit, Egbert F. ^{[11
]}

Thomas, Michael ^{[12
,13
]}

Iams, Wade T. ^{[14
]}

Cho, Byoung Chul ^{[15
]}

Kim, Hye Ryun ^{[15
]}

Yang, James Chih-Hsin ^{[16
]}

Chen, Yuh-Min ^{[17
,18
]}

Patel, Jyoti D. ^{[19
]}

Bestvina, Christine M. ^{[20
]}

Park, Keunchil ^{[21
]}

Griesinger, Frank ^{[22
]}

Johnson, Melissa ^{[23
]}

Gottfried, Maya ^{[24
]}

Britschgi, Christian ^{[25
]}

Heymach, John ^{[1
]}

Sikoglu, Elif ^{[26
]}

Berghoff, Karin ^{[27
]}

Schumacher, Karl-Maria ^{[28
]}

Bruns, Rolf ^{[29
]}

Otto, Gordon ^{[28
]}

Paik, Paul K. ^{[30
,31
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA

[2] Saitama Canc Ctr, Dept Thorac Oncol, Saitama, Japan

[3] Vall dHebron Inst Oncol VHIO, Dept Oncol, Barcelona, Spain

[4] CHU Bordeaux, Serv Malad Resp, Bordeaux, France

[5] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy

[6] Univ Chicago, Knapp Ctr Biomed Discovery, Dept Med, Sect Hematol Oncol, Chicago, IL USA

[7] Antwerp Univ Hosp UZA, Dept Pulmonol & Thorac Oncol, Edegem, Belgium

[8] Univ Lille, Inst Pasteur Lille, INSERM, CNRS,UMR9020,UMR S 1277,CHU Lille, Lille, France

[9] Hosp Univ Dexeus, Inst Oncol Dr Rosell, Grp Quiron Salud, Barcelona, Spain

[10] CHU Toulouse, Inst Univ Canc, Toulouse, France

[11] Netherlands Canc Inst, Dept Thorac Oncol, Amsterdam, Netherlands

[12] Heidelberg Univ, Thoraxklin, Heidelberg, Germany

[13] German Ctr Lung Res DZL, Translat Lung Res Ctr Heidelberg TLRC H, Heidelberg, Germany

[14] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA

[15] Yonsei Univ, Yonsei Canc Ctr, Coll Med, Seoul, South Korea

[16] Natl Taiwan Univ, Dept Med Oncol, Canc Ctr, Taipei, Taiwan

[17] Taipei Vet Gen Hosp, Dept Chest Med, Taipei, Taiwan

[18] Natl Yang Ming Univ, Sch Med, Taipei, Taiwan

[19] Northwestern Univ, Lurie Canc Ctr, Feinberg Sch Med, Chicago, IL USA

[20] Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA

[21] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Seoul, South Korea

[22] Univ Med Oldenburg, Univ Dept Internal Med Oncol, Pius Hosp, Dept Hematol & Oncol, Oldenburg, Germany

[23] Tennessee Oncol PLLC, Dept Med, Sarah Cannon Res Inst, Nashville, TN USA

[24] Meir Med Ctr, Dept Oncol, Tchernichovsky St 59, Kefar Sava, Israel

[25] Univ Hosp Zurich, Comprehens Canc Ctr Zurich, Dept Med Oncol & Hematol, Zurich, Switzerland

[26] Med Imaging, Patient Technol Solut, Calyx, Billerica, MA USA

[27] Healthcare Business Merck KGaA, Global Patient Safety, Darmstadt, Germany

[28] Healthcare Business Merck KGaA, Global Clin Dev, Darmstadt, Germany

[29] Healthcare Business Merck KGaA, Dept Biostat, Darmstadt, Germany

[30] Mem Sloan Kettering Canc Ctr, Thorac Oncol Serv, New York, NY USA

[31] Weill Cornell Med, Dept Med, New York, NY USA

来源：

CLINICAL CANCER RESEARCH | 2022年 / 28卷 / 06期

关键词：

CELL LUNG-CANCER; CAPMATINIB; MUTATIONS; AMPLIFICATION; INHIBITORS; DIAGNOSIS; SURVIVAL; IMPACT;

D O I：

10.1158/1078-0432.CCR-21-2733

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups. Patients and Methods: This phase 11, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An ad hoc retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity. Results: 152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7-53.0]. Patients aged <75 (n = 84) and >= 75 (n- 68) had ORRs of 48.8% (95% CI: 37.7-60.0) and 39.7% (95% CI: 28.0-52.3), respectively. Treatment-naive (n = 69) versus previously treated (n = 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32S-57A) vs. 44.6% (33/-55.9); median duration of response (95% CI): 10.8 (6.9-not estimable) vs. 11.1 (9.5-18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade >= 3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies. Conclusions: Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations.

引用

页码：1117 / 1126

页数：10

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