Efficacy of first-line treatments for advanced pulmonary sarcomatoid carcinomas: a real-world analysis

• Published in: ESMO open Vol. 10; no. 8; p. 105343
• Main Authors: Amrane, K., Cabarrou, B., Justeau, G., Schneider, S., Quantin, X., Falchero, L., Bigot, F., Ferrari, V., Guisier, F., Girard, N., Lena, H., Dansin, E., Madroszyk, A., Bizieux, A., Debieuvre, D., Perol, M., Simoneau, Y., Bosquet, L., Descourt, R., Chouaïd, C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2025; European Society for Medical Oncology; Elsevier
• Subjects: Aged; Cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; chemotherapy; Female; France; Humans; Immune Checkpoint Inhibitors - therapeutic use; immunotherapy; Life Sciences; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; NSCLC; Oncology; Original; PD-L1; pulmonary sarcomatoid carcinoma; Treatment Outcome; France; PD-L1; NSCLC; pulmonary sarcomatoid carcinoma; chemotherapy; immunotherapy
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2025.105343

Among the aggressive non-small-cell lung carcinoma subtypes, pulmonary sarcomatoid carcinoma (PSC) is a rare and poorly understood tumor. This study was undertaken to evaluate the efficacy [progression-free survival (PFS) and overall survival (OS)] of first-line immune checkpoint inhibitor (ICI) with or/without (±) chemotherapy (ChT) versus ChT alone against advanced PSCs (APSCs). Using the French Epidemiological Strategy and Medical Economics Lung Cancer (ESME-LC) database (2015-2022), we analyzed APSC patients’ first-line ICI ± ChT or ChT outcomes, then applied propensity score weighting to indirectly compare them. Among 42 219 patients with untreated lung cancers, 229 (0.5%) had APSCs. One hundred and sixty-one (70.3%) received first-line treatment (43 ICI alone, 24 ICI + ChT, 94 ChT alone): median age, 66 years; 70.2% men; 69.8% Eastern Cooperative Oncology Group performance status 0/1, among 106 available values; 86.2% smokers or former smokers. Molecular testing was done for 113/161 (70.2%) patients, 35.4% of whom had a molecular abnormality, most frequently a KRAS mutation (39.7%). Programmed death-ligand 1 tumor proportion scores determined for 43.5% of tumors (70/161) were: 68.6% ≥50%, 8.6% 1%-49%, and 22.9% <1%. For the ICI ± ChT group, median PFS and OS were 4.6 months [95% confidence interval (CI) 2.1-8.2 months] and 20.6 months (95% CI 10.3-32.4 months), respectively. For ChT-alone recipients, median PFS and OS were 2.2 months (95% CI 2.0-3.0 months) and 6.8 months (95% CI 4.3-10.0 months), respectively. Applying a propensity score, ICI ± ChT was significantly associated with longer PFS (HR 0.46, 95% CI 0.29-0.72, P < 0.001) and longer OS (HR 0.46, 95% CI 0.28-0.74, P = 0.002) than ChT alone. According to this real-world analysis, first-line ICI ± ChT seems to have considerably improved the prognosis of APSCs. •First-line ICI ± ChT for advanced pulmonary sarcomatoid carcinoma (APSC) prolongs PFS and OS versus ChT alone.•KRAS and MET mutations are frequent in APSC.•ICI ± ChT appears to be a promising first-line therapy for APSC.