Illini, Oliver and Saalfeld, Felix Carl and Christopoulos, Petros and Duruisseaux, Michael and Vikstroem, Anders and Peled, Nir and Demedts, Ingel and Dudnik, Elizabeth and Eisert, Anna and Hashemi, Sayed M. S. and Janzic, Urska and Kian, Waleed and Mohorcic, Katja and Mohammed, Saara and Silvoniemi, Maria and Rothschild, Sacha I. and Schulz, Christian and Wesseler, Claas and Addeo, Alfredo and Armster, Karin and Itchins, Malinda and Ivanovic, Marija and Kauffmann-Guerrero, Diego and Koivunen, Jussi and Kuon, Jonas and Pavlakis, Nick and Piet, Berber and Sebastian, Martin and Velthaus-Rusik, Janna-Lisa and Wannesson, Luciano and Wiesweg, Marcel and Wurm, Robert and Albers-Leischner, Corinna and Aust, Daniela E. and Janning, Melanie and Fabikan, Hannah and Herold, Sylvia and Klimova, Anna and Loges, Sonja and Sharapova, Yana and Schuetz, Maret and Weinlinger, Christoph and Valipour, Arschang and Overbeck, Tobias Raphael and Griesinger, Frank and Jakopovic, Marko and Hochmair, Maximilian J. and Wermke, Martin (2024) Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25 (7): 3992. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)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-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNOTHERAPY; PARAMETERS; MUTATIONS; IMPACT; non-small cell lung cancer; EGFR exon 20 inhibitors; mobocertinib; real-world data; exon 20 insertion |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Jul 2025 09:16 |
| Last Modified: | 23 Jul 2025 09:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65752 |
Actions (login required)
 |
View Item |
