Long-term survival with PD-1/PD-L1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in locally advanced or metastatic pulmonary lymphoepithelioma-like carcinoma: updated follow-up analysis.

[PURPOSE] Pulmonary lymphoepithelioma-like carcinoma (PLELC), a rare Epstein-Barr virus (EBV)-associated non-small-cell lung cancer (NSCLC) subtype, exhibits distinct clinicopathological features but lacks evidence-based first-line therapy. Our previous study demonstrated superior progression-free survival (PFS) with first-line immunotherapy plus chemotherapy (IO-Chemo) versus chemotherapy alone (Chemo). However, the long-term overall survival (OS) benefit remained uncertain. This study presents the final OS data with extended follow-up.

[METHODS] In this multicenter retrospective study, 133 patients with unresectable stage III-IV PLELC were stratified by first-line therapy: Chemo group (n = 78, platinum-based chemotherapy (PBC)) and IO-Chemo group (n = 55, PBC plus PD-1/PD-L1 inhibitors). The primary analysis in the study was OS.

[RESULTS] With a median follow-up of 102.6 months (Chemo group) and 48.5 months (IO-Chemo group), IO-Chemo demonstrated improved OS (median not reached vs. 25.6 months; HR 0.48, 95 % CI: 0.30-0.77; P = 0.0023) and PFS (median 15.7 vs. 7.6 months; HR 0.45, 95 % CI: 0.30-0.67; P < 0.0001), compared with chemotherapy alone. Salvage immunotherapy after first-line PBC was associated with prolonged OS compared to no subsequent immunotherapy (median 70.0 vs. 23.6 months, P = 0.0077). Multivariate analysis confirmed Eastern Cooperative Oncology Group (ECOG) performance status 0 (P < 0.001), first-line use of chemoimmunotherapy (P < 0.001) and low baseline EBV DNA levels (P = 0.019) as favorable prognostic factors, while liver metastasis (P < 0.001) and smoking (P = 0.011) were adverse ones.

[CONCLUSION] First-line immunotherapy combined with platinum-based chemotherapy is associated with long-term survival benefit in advanced PLELC. These findings support IO-Chemo as the preferred first-line regimen for this rare malignancy.

[ABBREVIATIONS] PLELC, Pulmonary lymphoepithelioma-like carcinoma; EBV, Epstein-Barr virus; NSCLC, non-small-cell lung cancer; PFS, progression-free survival; mPFS, median PFS; IO-Chemo, immunotherapy plus chemotherapy; Chemo, chemotherapy; OS, overall survival; mOS, median OS; PBC, platinum-based chemotherapy; PD-1, programmed cell death-1; PD-L1, programmed cell death-ligand 1; EBER-ISH, Epstein-Barr virus-encoded small RNA in situ hybridization; RECIST, Response Evaluation Criteria in Solid Tumors; TP, taxanes (paclitaxel or docetaxel) plus platinum; GP, gemcitabine plus platinum; ECOG PS, Eastern Cooperative Oncology Group performance status; NR, not reached; HR, hazard ratio; CI, confidence interval; ORR, the objective response rate; PR, partial response; SD, stable disease; PD, progressive disease; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; EGFR, epidermal growth factor receptor; AlK, anaplastic lymphoma kinase; SCLC, small cell lung cancer; NPC, nasopharyngeal carcinoma; IL-6, interleukin-6; TNF-α, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor; M-CSF, monocyte colony-stimulating factor; ICI, immune checkpoint inhibitor; TBP, treatment beyond progression.