Molecular Epidemiology and Treatment Patterns of Patients With EGFR Exon 20-Mutant NSCLC in the Precision Oncology Era: The European EXOTIC Registry.
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Mountzios Giannis, Planchard David, Metro Giulio, Tsiouda Dora, Prelaj Arsela, Lampaki Sofia, Shalata Walid, Riudavets Mariona, Christopoulos Petros, Girard Nicolas, Albarrán-Artahona Víctor, Garcia Campelo Rosario, Samitas Konstantinos, Banna Giuseppe Luigi, Boukovinas Ioannis, Agbarya Abed, Koumarianou Anna, Perdikouri Eleni-Isidora, Kosmidis Paris, Linardou Helena, Mauri David, Mavroudis Dimitrios, Athanasiadis Ilias, Kalofonos Haralambos, Xenidis Nikolaos, Korantzis Ippokratis, Ardavanis Alexandros, Rallis Grigorios, Bottiglieri Achille, Efthymiadis Konstantinos, Oikonomopoulos Georgios, Kokkalis Alexandros, Saloustros Emmanouil, Tsoukalas Nikolaos, Bartzi Dimitra, Economopoulou Panagiota, Psyrri Amanda, Reck Martin, Lo Russo Giuseppe
Аннотация
METHODS: We created a European registry for patients with advanced EGFR exon 20-mutant NSCLC diagnosed from January 2019 to December 2021. Patients enrolled in clinical trials were excluded. Clinicopathologic and molecular epidemiology data were collected, and treatment patterns were recorded. Clinical end points according to treatment assignment were assessed using Kaplan-Meier curves and Cox regression models.
RESULTS: Data on 175 patients from 33 centers across nine countries were included in the final analysis. Median age was 64.0 (range: 29.7-87.8) years. Main features included female sex (56.3%), never or past smokers (76.0%), adenocarcinoma (95.4%), and tropism for bone (47.4%) and brain (32.0%) metastases. Mean programmed death-ligand 1 tumor proportional score was 15.8% (range: 0%-95%) and mean tumor mutational burden was 7.06 (range: 0-18.8) mutations per megabase. Exon 20 was detected in the tissue (90.7%), plasma (8.7%), or both (0.6%), using mostly targeted next-generation sequencing (64.0%) or polymerase chain reaction (26.0%). Mutations were mainly insertions (59.3%), followed by duplications (28.1%), deletions-insertions (7.7%), and the T790M (4.5%). Insertions and duplications were located mainly in the near loop (codons 767-771, 83.1%) and the far loop (codons 771-775, 13%) and only in 3.9% within the C helix (codons 761-766). Main co-alterations included mutations in TP53 (61.8%) and MET amplifications (9.4%). Treatment on mutation identification included chemotherapy (CT) (33.8%), CT-immunotherapy (IO) (18.2%), osimertinib (22.1%), poziotinib (9.1%), mobocertinib (6.5%), mono-IO (3.9%), and amivantamab (1.3%). Disease control rates were 66.2% with CT plus or minus IO, 55.8% with osimertinib, 64.8% with poziotinib, and 76.9% with mobocertinib. Corresponding median overall survival was 19.7, 15.9, 9.2, and 22.4 months, respectively. In multivariate analysis, type of treatment (new targeted agents versus CT ± IO) affected progression-free survival (p = 0.051) and overall survival (p = 0.03).
CONCLUSIONS: EXOTIC represents the largest academic real-world evidence data set on EGFR exon 20-mutant NSCLC in Europe. Indirectly compared, treatment with new exon 20-targeting agents is likely to confer survival benefit than CT plus or minus IO.