Real-world evidence (RWE) regarding molecular epidemiology and management patterns of patients with epidermal growth factor receptor (EGFR) exon-20 mutated, advanced non-small-cell lung cancer (NSCLC) outside the context of clinical trials are lacking.
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. Clinicopathological and molecular epidemiology data were collected and treatment patterns were recorded. Clinical endpoints according to treatment assignment were assessed using Kaplan-Meier curves and Cox-regression models.
Data on 175 patients from 33 centers across 9 countries were included in final analysis. Median age was 64.0 years (range 29.7-87.8); Main features included female sex (56.3%), never/past smokers (76.0%), adenocarcinoma (95.4%) and tropism for bone (47.4%) and brain (32.0%) metastases. Mean PD-L1 TPS score was 15.8% (range 0-95) and mean TMB was 7.06 mut/MB (range 0-18.8). Exon 20 was detected in tissue (90.7%), in plasma (8.7%) or both (0.6%), using mostly targeted NGS (64.0%) or PCR (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 upon mutation identification included chemotherapy (CT), (33.8%), chemo-immunotherapy (CT-IO) (18.2%), osimertinib (22.1%), poziotinib (9.1%), mobocertinib (6.5%), mono-immunotherapy (3.9%) and amivantamab (1.3%). Disease control rates were 66.2% with CT+/- IO, 55.8% with osimertinib, 64.8% with poziotinib and 76.9% with mobocertinib. Corresponding median survival (OS) was 19.7, 15.9, 9.2 and 22.4 months respectively. In multivariate analysis, type of treatment (new targeted agents vs Chemo+/-IO) affected PFS (p=0.051) and OS (p=0.03).
EXOTIC represents the largest academic RWE dataset on EGFR exon 20-mutant NSCLC in Europe. Indirectly compared, treatment with new exon 20-targeting agents is likely to confer survival benefit over chemo+/-IO.