International Journal of Molecular Sciences (Apr 2024)
Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis
- Oliver Illini,
- Felix Carl Saalfeld,
- Petros Christopoulos,
- Michaël Duruisseaux,
- Anders Vikström,
- Nir Peled,
- Ingel Demedts,
- Elizabeth Dudnik,
- Anna Eisert,
- Sayed M. S. Hashemi,
- Urska Janzic,
- Waleed Kian,
- Katja Mohorcic,
- Saara Mohammed,
- Maria Silvoniemi,
- Sacha I. Rothschild,
- Christian Schulz,
- Claas Wesseler,
- Alfredo Addeo,
- Karin Armster,
- Malinda Itchins,
- Marija Ivanović,
- Diego Kauffmann-Guerrero,
- Jussi Koivunen,
- Jonas Kuon,
- Nick Pavlakis,
- Berber Piet,
- Martin Sebastian,
- Janna-Lisa Velthaus-Rusik,
- Luciano Wannesson,
- Marcel Wiesweg,
- Robert Wurm,
- Corinna Albers-Leischner,
- Daniela E. Aust,
- Melanie Janning,
- Hannah Fabikan,
- Sylvia Herold,
- Anna Klimova,
- Sonja Loges,
- Yana Sharapova,
- Maret Schütz,
- Christoph Weinlinger,
- Arschang Valipour,
- Tobias Raphael Overbeck,
- Frank Griesinger,
- Marko Jakopovic,
- Maximilian J. Hochmair,
- Martin Wermke
Affiliations
- Oliver Illini
- Department of Respiratory and Critical Care Medicine, Klinik Floridsdorf, Vienna Healthcare Group, Bruenner Straße 68, A-1210 Vienna, Austria
- Felix Carl Saalfeld
- Clinic for Internal Medicine I, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany
- Petros Christopoulos
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Michaël Duruisseaux
- Respiratory Department and Early Phase, Louis Pradel Hospital, Hospices Civils de Lyon Cancer Institute, 69002 Lyon, France
- Anders Vikström
- Department of Pulmonary Medicine, University Hospital Linköping, 58185 Linköping, Sweden
- Nir Peled
- The Hemsely Cancer Center, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
- Ingel Demedts
- Department of Pulmonary Diseases, AZ Delta, Deltalaan 1, 8800 Roeselare, Belgium
- Elizabeth Dudnik
- Head, Thoracic Oncology Service, Assuta Medical Centers, Tel-Aviv 6329302, Israel
- Anna Eisert
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Sayed M. S. Hashemi
- Department of Pulmonary Medicine, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, 1081 Amsterdam, The Netherlands
- Urska Janzic
- Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia
- Waleed Kian
- The Hemsely Cancer Center, Shaare Zedek Medical Center, Jerusalem 9103102, Israel
- Katja Mohorcic
- Medical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia
- Saara Mohammed
- Kent Oncology Centre, Maidstone and Tunbridge Wells NHS Trust, Kent TN24QJ, UK
- Maria Silvoniemi
- Department of Pulmonary Diseases, Turku University Hospital, University of Turku, 20014 Turku, Finland
- Sacha I. Rothschild
- Center for Oncology & Hematology and Comprehensive Cancer Center, Cantonal Hospital Baden, 5404 Baden, Switzerland
- Christian Schulz
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Claas Wesseler
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Alfredo Addeo
- Oncology Department, University Hospital Geneva, 1205 Geneva, Switzerland
- Karin Armster
- Department of Pneumology, Universitätsklinikum Krems, 3500 Krems an der Donau, Austria
- Malinda Itchins
- Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
- Marija Ivanović
- Department of Oncology, University Medical Centre Maribor, 2000 Maribor, Slovenia
- Diego Kauffmann-Guerrero
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Jussi Koivunen
- Department of Oncology and Radiotherapy, Oulu University Hospital, 90014 Oulu, Finland
- Jonas Kuon
- Department Thoracic Oncology, SLK Fachklinik Löwenstein, 74245 Löwenstein, Germany
- Nick Pavlakis
- Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
- Berber Piet
- Department of Respiratory Medicine, Radboudumc, 6225 GA Nijmegen, The Netherlands
- Martin Sebastian
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Janna-Lisa Velthaus-Rusik
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Luciano Wannesson
- Istituto Oncologico della Svizzera Italiana, 6500 Bellinzona, Switzerland
- Marcel Wiesweg
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Robert Wurm
- Division of Pulmonology, Department of Internal Medicine, LKH-Universitätsklinikum, Medical University of Graz, 8036 Graz, Austria
- Corinna Albers-Leischner
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Daniela E. Aust
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Melanie Janning
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Hannah Fabikan
- Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, A-1210 Vienna, Austria
- Sylvia Herold
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Anna Klimova
- Core Unit for Data Management and Analytics, National Center for Tumor Diseases, 01307 Dresden, Germany
- Sonja Loges
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Yana Sharapova
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Maret Schütz
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Christoph Weinlinger
- Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, A-1210 Vienna, Austria
- Arschang Valipour
- Department of Respiratory and Critical Care Medicine, Klinik Floridsdorf, Vienna Healthcare Group, Bruenner Straße 68, A-1210 Vienna, Austria
- Tobias Raphael Overbeck
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Frank Griesinger
- National Network Genomic Medicine Lung Cancer (nNGM), 50937 Cologne, Germany
- Marko Jakopovic
- Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, 10000 Zagreb, Croatia
- Maximilian J. Hochmair
- Department of Respiratory and Critical Care Medicine, Klinik Floridsdorf, Vienna Healthcare Group, Bruenner Straße 68, A-1210 Vienna, Austria
- Martin Wermke
- Clinic for Internal Medicine I, University Hospital Carl Gustav Carus, TU Dresden, 01307 Dresden, Germany
- DOI
- https://doi.org/10.3390/ijms25073992
- Journal volume & issue
-
Vol. 25,
no. 7
p. 3992
Abstract
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-naïve 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.
Keywords