Evidence map›Paper›PMID 42710274›Full record

ArticleESMO open2026

Osimertinib in advanced non-small cell lung cancer (NSCLC) harboring different EGFR uncommon variants: real-world data from the Italian biomarker ATLAS database.

G Farinea, A Mogavero, A Vitale, E Roca, V Scotti, A Delmonte, A Veccia, M L Reale, P Bironzo, C Genova and 7 more

Abstract read
In one paragraph

Article in ESMO open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

G FarineaDepartment of Oncology, University of Turin, AOU S. Luigi Gonzaga, Orbassano, Italy.
A MogaveroDepartment of Oncology, University of Turin, AOU S. Luigi Gonzaga, Orbassano, Italy.
A VitaleDepartment of Oncology, Università Cattolica del Sacro Cuore, Rome, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
E RocaThoracic Oncology-Lung Unit, P. Pederzoli Hospital, Peschiera Del Garda, Italy.
V ScottiRadiation Therapy Unit, Department of Oncology, Careggi University Hospital, Florence, Italy.
A DelmonteMedical Oncology Department, IRCCS IRST "Dino Amadori", Meldola, Italy.
A VecciaUnit of Oncology, Santa Chiara Regional Hospital, APSS, Trento, Italy.
M L RealeMedical Oncology Unit, "Vito Fazzi" Hospital, Lecce, Italy.
P BironzoDepartment of Oncology, University of Turin, AOU S. Luigi Gonzaga, Orbassano, Italy.
C GenovaDepartment of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy; Academic Medical Oncology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
D GalettaThoracic Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
A BulottaDepartment of Oncology, IRCCS Ospedale San Raffaele, Milan, Italy.
F GrossiDivision of Medical Oncology, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
D CortinovisDepartment of Medicine, Università Milano-Bicocca, Milan, Italy; Medical Oncology Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy.
S NovelloDepartment of Oncology, University of Turin, AOU S. Luigi Gonzaga, Orbassano, Italy. Electronic address: silvia.novello@unito.it.
E BriaDepartment of Oncology, Università Cattolica del Sacro Cuore, Rome, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Oncology Unit, Ospedale Isola Tiberina-Gemelli Isola, Rome, Italy.
F PassigliaDepartment of Oncology, University of Turin, AOU S. Luigi Gonzaga, Orbassano, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundUncommon EGFR mutations (ucEGFR mut) account for 10%-15% of epidermal growth factor receptor (EGFR) oncogenic alterations in non-small cell lung cancer (NSCLC) and display heterogeneous sensitivity to EGFR tyrosine kinase inhibitors. MATERIALS AND

methodsClinical, pathological, and molecular data from patients with advanced NSCLC harboring ucEGFR mut (excluding ex20 insertions) and treated with first-line osimertinib were retrospectively collected from the Italian ATLAS registry.

resultsFrom January 2019 to January 2025, 212 patients were included. Median age was 69 years (range 24-90); 61.3% were female and 47.6% had a smoking history. Exon 19 deletions/insertions (ex19 delins) were the most frequent ucEGFR mut (55.7%), followed by L816Q (10.8%), G719X (8.5%), and D761N (7.5%). Tumor protein p53 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) comutations were present in 43.3% and 10.4% of cases. The overall response rate (ORR) was 66% [95% confidence interval (CI) 58-73], median progression-free survival (mPFS) was 18.3 months (95% CI 14.6-19.7), and median overall survival (mOS) was 34.5 months (95% CI 26.1-42.9). Patients with ex19 delins showed superior outcomes versus other ucEGFR mut: ORR (74.3% versus 55%, P = 0.007), mPFS (25.3 versus 12.6 months, P = 0.001), and mOS (41.7 versus 30.4 months, P = 0.03), as well as different resistance mechanisms. Targetable acquired alterations (mesenchymal-epithelial transition amplification and C797S mutations) were detected predominantly in patients with ex19 delins, leading to the use of second-line molecularly matched therapies mainly in this subgroup. Patients with ex19 delins showed similar survival outcomes (25.3 versus 25.4 months, P = 0.55) and resistance patterns compared with a cohort of patients harboring the common exon 19 deletion (ELREA) extracted from the ATLAS registry. Among ex19 delins, variants starting at codon 746 achieved longer survival compared with those starting at codon 747.

conclusionsOsimertinib exhibited meaningful differences in efficacy and resistance mechanisms across distinct ucEGFR mut. Notably, ex19 delins showed comparable survival outcomes and resistance patterns to classical ex19 deletions, albeit with heterogeneous osimertinib sensitivity depending on the deletion-insertion starting codon.

Indexed as

exon 19 deletions–insertions (ex19 delins)non-small-cell lung cancerosimertinibtyrosine kinase inhibitorsuncommon EGFR mutation

Identifiers

PMID42710274
PMCPMC13573738

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