First-line treatment for unresectable pulmonary lymphoepithelial carcinoma: A real-world comparison of platinum-based doublet chemotherapy with or without PD-1 inhibitors.

BACKGROUND

Pulmonary lymphoepithelial carcinoma (PLEC) is a rare malignancy with limited evidence for unresectable disease. We compared platinum-based doublet chemotherapy with or without programmed cell death 1 (PD-1) inhibition and explored regimen-specific outcomes.

PATIENTS AND

METHODS

Consecutive patients with unresectable stage IIIA-IVB PLEC receiving gemcitabine-platinum (GP), taxane-platinum (TP), or pemetrexed-platinum (AP), alone (Chemo-alone) or with PD-1 inhibition (Chemo-IO), were retrospectively included. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Survival was estimated using Kaplan-Meier and Cox models, with OS analyses administratively censored at 60 months; inverse probability of treatment weighting (IPTW) was used as a sensitivity analysis.

RESULTS

Among 132 patients, 70 received Chemo-alone and 62 received Chemo-IO. Chemo-IO was associated with longer PFS (median 16.4 vs 6.4 months; HR 0.23; 95% CI, 0.13-0.41; P < 0.001) and longer OS in unweighted analysis (59.6 vs 36.9 months; HR 0.59; 95% CI, 0.36-0.99; P = 0.044). ORR was higher with Chemo-IO (80.6% vs 58.6%; P = 0.008), whereas DCR was similar (95.2% vs 88.6%; P = 0.216). In exploratory regimen-level analyses, Chemo-alone median PFS was 9.0, 6.0, and 4.3 months with GP, TP, and AP; GP showed a favorable PFS signal compared with TP (HR, 0.35; 95% CI, 0.15-0.82; P = 0.016) and AP (HR, 0.29; 95% CI, 0.13-0.69; P = 0.005). PFS and OS did not differ significantly across Chemo-IO regimens. IPTW supported the PFS finding but attenuated the OS association.

CONCLUSIONS

In this retrospective cohort, first-line Chemo-IO was associated with longer PFS and higher ORR, whereas OS findings should be interpreted cautiously. The favorable GP signal observed in the Chemo-alone setting was exploratory, and regimen-level differences were less evident after immunotherapy was incorporated. These findings may inform treatment selection and support prospective studies.