WCLC 2025 - Posters & ePosters-P1.11.42 Dual Immune Checkpoint Blockade With CTLA-4 and PD-(L)1 Inhibitors in NSCLC: A Reconstructed Patient Data Meta-Analysis

P1.11.42 Dual Immune Checkpoint Blockade With CTLA-4 and PD-(L)1 Inhibitors in NSCLC: A Reconstructed Patient Data Meta-Analysis

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This study systematically reviewed and meta-analyzed individual patient data from phase III randomized clinical trials to assess the long-term overall survival (OS) impact of dual immune checkpoint inhibition (CTLA-4 plus PD-(L)1 inhibitors) versus PD-(L)1 monotherapy in advanced non-small cell lung cancer (NSCLC). The motivation was to clarify which patient subgroups benefit most from adding CTLA-4 blockade, as immune checkpoint inhibitors are standard care but patient selection remains unclear.<br /><br />Data were extracted from published Kaplan-Meier survival curves including trials such as CheckMate 227 and 9LA, POSEIDON, Keynote-189, 407, and IMpower 150. These trials involved various PD-(L)1 and CTLA-4 inhibitor combinations, alone or with chemotherapy, with follow-up data at five years. The analysis also included biomarker stratifications by PD-L1 tumor proportion score (TPS), histology, and mutational status of KRAS and STK11 genes, which are relevant for NSCLC biology and treatment response.<br /><br />Key findings include that dual CTLA-4 and PD-(L)1 blockade significantly improved OS compared to PD-(L)1 monotherapy in patients with PD-L1 TPS ≥1%. Notably, patients with STK11 mutations—a subgroup typically associated with poor prognosis and reduced immunotherapy response—showed greater survival benefit from dual blockade. These results suggest that combining CTLA-4 inhibitors with PD-(L)1 inhibitors can overcome resistance in some molecularly defined NSCLC subpopulations.<br /><br />In conclusion, the data support personalized immunotherapy approaches in advanced NSCLC. Dual immune checkpoint inhibition may offer superior long-term survival particularly for patients with PD-L1 expression of at least 1% and those harboring STK11 mutations, guiding clinicians in optimizing immunotherapy combinations based on tumor biomarkers.

Asset Subtitle

Alessandro Di Federico

Meta Tag

Speaker Alessandro Di Federico

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

dual immune checkpoint inhibition

CTLA-4 inhibitors

PD-(L)1 inhibitors

non-small cell lung cancer

overall survival

PD-L1 tumor proportion score

STK11 mutations

KRAS mutations

phase III randomized clinical trials

personalized immunotherapy