20.500.12556/DiRROS-19118 Mobocertinib in patients with EGFR exon 20 insertion-positive non-small cell lung cancer (MOON) an international real-world safety and efficacy analysis 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. medicina non-small cell lung cancer EGFR exon 20 inhibitors mobocertinib real-world data exon 20 insertion medicina ne-drobnocelični pljučni rak zaviralci insercije v eksonu 20 EGFR mobocertinib podatki iz resničnega življenja insercija v eksonu 20 true false true MDPI Švica Angleški jezik Slovenski jezik © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Neznano 2024-06-19 08:02:08 2024-06-19 08:02:08 2024-07-03 03:39:44 0000-00-00 00:00:00 2024 0 0 Soavtorji: Urška Janžič, Katja Mohorčič, Marija Ivanović; Nasl. z nasl. zaslona; Opis vira z dne 10. 4. 2024; str. 1-19 iss. 7, [article no.] 3992 Vol. 25 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2024-02-26 2024-03-29 2024-04-03 616.24 1422-0067 10.3390/ijms25073992 192029955 https://www.mdpi.com/1422-0067/25/7/3992 1 77ce7e5e-2e01-11ef-9c9e-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26307 ijms-25-03992-v3.pdf ijms-25-03992-v3.pdf 1 92CF0D9185E6D52F5FA66F5C9936A0C3 1826a917c949f0bf8b12339fe3a2a46f524038d864a6440c45e582da05ff04a3 f0578f3a-385a-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26365 Univerzitetna klinika za pljučne bolezni in alergijo Golnik 0 0 0