Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis

被引：3

作者：

Illini, Oliver ^{[1
,2
]}

Saalfeld, Felix Carl ^{[3
,4
,5
]}

Christopoulos, Petros ^{[5
,6
]}

Duruisseaux, Michael ^{[7
,8
,9
]}

Vikstroem, Anders ^{[10
]}

Peled, Nir ^{[11
]}

Demedts, Ingel ^{[12
]}

Dudnik, Elizabeth ^{[13
,14
]}

Eisert, Anna ^{[5
,15
]}

Hashemi, Sayed M. S. ^{[16
]}

Janzic, Urska ^{[17
,18
]}

Kian, Waleed ^{[11
,19
]}

Mohorcic, Katja ^{[17
]}

Mohammed, Saara ^{[20
]}

Silvoniemi, Maria ^{[21
]}

Rothschild, Sacha I. ^{[22
]}

Schulz, Christian ^{[5
,23
]}

Wesseler, Claas ^{[5
,24
]}

Addeo, Alfredo ^{[25
]}

Armster, Karin ^{[26
]}

Itchins, Malinda ^{[27
,28
]}

Ivanovic, Marija ^{[29
]}

Kauffmann-Guerrero, Diego ^{[5
,30
]}

Koivunen, Jussi ^{[31
,32
,33
]}

Kuon, Jonas ^{[34
]}

Pavlakis, Nick ^{[27
,28
]}

Piet, Berber ^{[35
]}

Sebastian, Martin ^{[5
,36
]}

Velthaus-Rusik, Janna-Lisa ^{[5
,37
]}

Wannesson, Luciano ^{[38
]}

Wiesweg, Marcel ^{[5
,39
]}

Wurm, Robert ^{[40
]}

Albers-Leischner, Corinna ^{[5
,37
]}

Aust, Daniela E. ^{[5
,41
]}

Janning, Melanie ^{[5
,42
,43
,44
,45
]}

Fabikan, Hannah ^{[2
]}

Herold, Sylvia ^{[5
,41
]}

Klimova, Anna ^{[46
]}

Loges, Sonja ^{[5
,42
,43
,44
,45
]}

Sharapova, Yana ^{[5
,42
,43
,44
,45
]}

Schuetz, Maret ^{[5
,41
]}

Weinlinger, Christoph ^{[2
]}

Valipour, Arschang ^{[1
,2
]}

Overbeck, Tobias Raphael ^{[5
,47
]}

Griesinger, Frank ^{[5
,48
]}

Jakopovic, Marko ^{[49
,50
]}

Hochmair, Maximilian J. ^{[1
,2
]}

Wermke, Martin ^{[3
,4
,5
]}

机构：

[1] Vienna Healthcare Grp, Klin Floridsdorf, Dept Resp & Crit Care Med, Bruenner Str 68, A-1210 Vienna, Austria

[2] Karl Landsteiner Inst Lung Res & Pulm Oncol, A-1210 Vienna, Austria

[3] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Clin Internal Med 1, D-01307 Dresden, Germany

[4] Natl Ctr Tumor Dis, D-01307 Dresden, Germany

[5] Natl Network Genom Med Lung Canc nNGM, D-50937 Cologne, Germany

[6] Thoraxklin & Translat Lung Res Ctr TLRC, D-69120 Heidelberg, Germany

[7] Louis Pradel Hosp, Hosp Civils Lyon Canc Inst, Resp Dept & Early Phase, F-69002 Lyon, France

[8] Ctr Natl Rech Sci CNRS 5286, Unite Mixte Rech UMR Inst Natl Sante & Rech Med IN, Canc Res Ctr Lyon, Oncopharmacol Lab, Lyon, France

[9] Univ Claude Bernard, Univ Lyon, F-69622 Lyon, France

[10] Univ Hosp Linkoping, Dept Pulm Med, S-58185 Linkoping, Sweden

[11] Shaare Zedek Med Ctr, Hemsely Canc Ctr, IL-9103102 Jerusalem, Israel

[12] AZ Delta, Dept Pulm Dis, Deltalaan 1, B-8800 Roeselare, Belgium

[13] Assuta Med Ctr, Head Thorac Oncol Serv, IL-6329302 Tel Aviv, Israel

[14] Ben Gurion Univ Negev, Fac Hlth Sci, IL-84105 Beer Sheva, Israel

[15] Univ Hosp Cologne, Ctr Integrated Oncol Aachen Bonn Cologne Duesseld, Dept Internal Med 1, Lung Canc Grp Cologne, D-50937 Cologne, Germany

[16] VU Univ Med Ctr VUmc, Amsterdam UMC, Canc Ctr Amsterdam, Dept Pulm Med, NL-1081 HV Amsterdam, Netherlands

[17] Univ Ljubljana, Med Fac, Ljubljana 1000, Slovenia

[18] Univ Clin Golnik, Med Oncol Unit, Golnik 4204, Slovenia

[19] Assuta Ashdod Univ Hosp, Inst Oncol, Ashdod 7747629, Israel

[20] Kent Oncol Ctr, Maidstone & Tunbridge Wells NHS Trust, Kent TN24QJ, England

[21] Univ Turku, Turku Univ Hosp, Dept Pulm Dis, Turku 20014, Finland

[22] Cantonal Hosp Baden, Ctr Oncol & Hematol, Comprehens Canc Ctr, CH-5404 Baden, Switzerland

[23] Univ Hosp Regensburg, Dept Internal Med 2, D-93053 Regensburg, Germany

[24] Klinikum Harburg, Asklepios Tumorzentrum Hamburg, Dept Pneumol, D-21075 Hamburg, Germany

[25] Univ Hosp Geneva, Oncol Dept, CH-1205 Geneva, Switzerland

[26] Dept Pneumol, Univ Klinikum Krems, A-3500 Krems An Der Donau, Austria

[27] Royal North Shore Hosp, Dept Med Oncol, St Leonards, NSW 2065, Australia

[28] Univ Sydney, Northern Clin Sch, St Leonards, NSW 2065, Australia

[29] Univ Med Ctr Maribor, Dept Oncol, Maribor 2000, Slovenia

[30] Univ Hosp, Univ Munich LMU, Thorac Oncol Ctr Munich, Dept Med 5, D-81377 Munich, Germany

[31] Oulu Univ Hosp, Dept Oncol & Radiotherapy, Oulu 90014, Finland

[32] Univ Oulu, Canc & Translat Med Res Unit, Oulu 90014, Finland

[33] Med Res Ctr Oulu, Oulu 90014, Finland

[34] SLK Fachklin Lowenstein, Dept Thorac Oncol, D-74245 Lowenstein, Germany

[35] Radboudumc, Dept Resp Med, NL-6225 GA Nijmegen, Netherlands

[36] Univ Hosp, Univ Frankfurt, Dept Med Hematol Oncol, D-60596 Frankfurt, Germany

[37] Univ Med Ctr Hamburg Eppendorf, Dept Oncol Hematol & Bone Marrow Transplantat, Sect Pneumol, Hubertus Wald Comprehens Canc Ctr Hamburg, D-20251 Hamburg, Germany

[38] Ist Oncol Svizzera Italiana, CH-6500 Bellinzona, Switzerland

[39] Univ Duisburg Essen, West German Canc Ctr, Dept Med Oncol, D-45147 Essen, Germany

[40] Med Univ Graz, Dept Internal Med, Div Pulmonol, LKH Univ Klinikum, A-8036 Graz, Austria

[41] Univ Hosp Carl Gustav Carus, TU Dresden, Dept Pathol, D-01307 Dresden, Germany

[42] Univ Med Ctr Mannheim, DKFZ Hector Canc Inst, D-68167 Mannheim, Germany

[43] Heidelberg Univ, Univ Hosp Mannheim, Dept Personalized Oncol, D-68167 Mannheim, Germany

[44] German Canc Res Ctr, Div Personalized Med Oncol, D-69120 Heidelberg, Germany

[45] German Ctr Lung Res DZL, D-69120 Heidelberg, Germany

[46] Natl Ctr Tumor Dis NCT, Core Unit Data Management & Analyt, D-01307 Dresden, Germany

[47] Univ Med Ctr Gottingen, Dept Hematol & Med Oncol, Gottingen Univ, D-37075 Gottingen, Germany

[48] Pius Univ Hosp, Univ Med Oldenburg, Dept Hematol & Oncol, D-26121 Oldenburg, Germany

[49] Univ Hosp Ctr Zagreb, Dept Resp Dis Jordanovac, Zagreb, Croatia

[50] Univ Zagreb, Sch Med, Zagreb 10000, Croatia

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 07期

关键词：

non-small cell lung cancer; EGFR exon 20 inhibitors; mobocertinib; real-world data; exon; 20; insertion; IMMUNOTHERAPY; PARAMETERS; MUTATIONS; IMPACT;

D O I：

10.3390/ijms25073992

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade >= 3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naive patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.

引用

页数：19

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