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Background
The efficacy of checkpoint inhibitors for non-small cell lung cancer (NSCLC) with MET exon 14 skipping (METΔ14ex) remains controversial.
Materials and methods
110 consecutive METΔ14ex NSCLC patients receiving first-line chemotherapy (CHT) and/or immunotherapy (IO) in 10 German centers between 2016–2022 were analyzed.
Results
Combined CHT-IO was given to 35/110 (32%) patients, IO alone to 43/110 (39%), and CHT to 32/110 (29%) upfront. Compared to CHT, CHT-IO showed longer progression-free survival (median PFS 6 vs. 2.5 months, p = 0.004), more objective responses (ORR 49% vs. 28%, p = 0.086) and numerically longer overall survival (OS 16 vs. 10 months, p = 0.240). For IO monotherapy, OS (14 vs. 16 months) and duration of response (26 vs. 22 months) were comparable to those of CHT-IO. Primary progressive disease (PD) was more frequent with IO compared to CHT-IO (13/43 vs. 3/35, p = 0.018), particularly for never-smokers (p = 0.041). Higher PD-L1 TPS were not associated with better IO outcomes, but TP53 mutated tumors showed numerically improved ORR (56% vs. 32%, p = 0.088) and PFS (6 vs. 3 months, p = 0.160), as well as longer OS in multivariable analysis (HR=0.54, p = 0.034) compared to their wild-type counterparts. Any second-line treatment was administered to 35/75 (47%) patients, with longer survival for capmatinib or tepotinib compared to crizotinib (PFS 10 vs. 3 months, p = 0.013; OS 16 vs. 13 months, p = 0.270).
Conclusion
CHT-IO is superior to CHT, and IO alone also effective for METΔ14ex NSCLC, especially in the presence of TP53 mutations and independent of PD-L1 expression, but never-smokers are at higher risk of primary PD.
Real-life characteristics and management of patients with fibrosing interstitial lung disease
(2025)
This study aims to report real-life data on the characteristics and treatment patterns of patients with fibrosing interstitial lung disease (ILD; except idiopathic pulmonary fibrosis) across multiple specialised centres in Germany. Eligibility criteria included ILD affecting >10% of lung parenchyma on high-resolution computed tomography, a single breath diffusion capacity for carbon monoxide (DLCO) ≤80% predicted and active treatment of lung disease.
Methods
As of the interim analysis cut-off, 655 patients (mean±sd age 65.9±11.7 years, 54.5% male) were included. The most common ILD subtypes were fibrosing hypersensitivity pneumonitis (31.2%), fibrosing ILD (22.0%), rheumatoid arthritis and connective tissue disease ILDs (13.0%) and unclassifiable fibrosing ILD (13.0%).
Results
Lung function metrics included total lung capacity at 68.3±17.6% predicted, forced vital capacity at 69.8±19.8% predicted, forced expiratory volume in 1 s at 73.7±19.5% predicted and DLCO at 33.8±15.6% predicted. Current treatments included oral steroids (62.6%), antifibrotic therapy (50.7%), azathioprine (14.4%), methotrexate (10.2%) and mycophenolate mofetil (11.1%). Patients on antifibrotic therapy were typically older at diagnosis and registry inclusion, more often male, had more comorbidities, a lower 6-min walk distance and reduced lung function metrics compared with those not on antifibrotic therapy. Notably, 27.3% of the patients on antifibrotic therapy did not meet progression criteria (INBUILD), whereas 40.1% of patients not receiving antifibrotic therapy did meet those criteria.
Conclusion
The patient characteristics observed align with those observed in randomised controlled trials and other noninterventional studies. Patients on antifibrotic therapy generally had more severe disease profiles.