Efficacy of immune therapy–based regimens in sarcomatoid lung cancer: A systematic review and meta-analysis.

Abstract

e20769 Background: Sarcomatoid lung cancer/Pulmonary Sarcomatoid Carcinoma (PSC) is a rare, poorly differentiated, chemoresistant, highly aggressive variant of non-small-cell lung cancer (NSCLC) with poor outcomes with conventional cytotoxic therapy. Immune checkpoint inhibitors (ICIs) that restore antitumor T-cell activity are effective in PSC due to high PD-L1 expression, mutational burden, immune infiltration, and distinct genomic landscape involving TP53, KRAS, MET exon 14 skipping, and chromatin remodeling, differentiating them from classic oncogene (EGFR/ALK)-driven Non Small-Cell Lung Cancer, which often exhibits immune exclusion and ICI Resistance. Retrospective cohorts have shown that immunotherapy-based approaches yield higher OS and PFS than chemotherapy, with emerging evidence in the neoadjuvant and adjuvant settings. Methods: This Systematic Review and meta-analysis evaluated immunotherapy-based systemic treatments and non-immunotherapy regimens in adults with PSC across all (I-IV) disease stages, including recurrent/metastatic cases, and was conducted per PRISMA guidelines, using PubMed, Embase, and the Cochrane Library till October 2025. Studies that were single-arm studies, non-human, non-English, non-dedicated or lacked full-text availability were excluded. Immunotherapy interventions, ICI monotherapy/dual-therapy, or ICI-chemotherapy combinations, were compared with other non-ICI regimens. Primary outcomes included overall survival (OS) and objective response rate (ORR). Secondary outcomes included progression-free survival (PFS). Disease control rate (DCR) and treatment-related adverse events couldn’t be analyzed due to incomplete reporting across studies. A random effects model was used, with outcomes reported as odds ratios (ORs) or hazard ratios (HRs), with 95% CIs, statistical significance set at p < 0.05, and heterogeneity assessed using the I 2 statistic, with I 2 < 75% considered highly heterogeneous. Results: Five Retrospective two arm studies met the inclusion criteria. ICI-based regimens had higher OS/Overall Survival reported in 5 studies (HR 0.46, 95% CI 0.32-0.64; p = 0.003, I² = 11.5%), PFS/Progression Free Survival reported in 3 studies (HR 0.44, 95% CI 0.20-1.00; p = 0.049, I² = 26.3%). Objective response rate (ORR), evaluated in two small studies, numerically favored immunotherapy but did not reach statistical significance (OR 4.87, 95% CI 0.001-37,218; p = 0.27) and was limited by wide confidence intervals and small sample size. Conclusions: This Meta-analysis showed significant survival benefits with Immunotherapy-based regimens compared with conventional chemotherapy in PSC. RCT’s are precluded due to the rarity of sarcomatoid lung cancer, and the benefit consistency across various disease stages and treatment lines remains uncertain, warranting more systematic evidence/research in this area.