2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.03 Clinical outcomes and predictors of response to PD-(L)1 blockade in patients with oncogene-driver negative NSCLC who have never smoked

PP01.03 Clinical outcomes and predictors of response to PD-(L)1 blockade in patients with oncogene-driver negative NSCLC who have never smoked

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This study examines clinical outcomes and response predictors for PD-(L)1 blockade therapy in patients with metastatic non-small cell lung cancer (NSCLC) who have never smoked and have no oncogene drivers. It involved data from patients treated at five academic cancer centers in both the US and Europe. Patients' clinicopathologic characteristics and outcomes were analyzed to identify factors linked to a favorable response to immune checkpoint inhibitors (ICIs).<br /><br />Key findings indicate that high PD-L1 expression (greater than 1%) and a very high tumor mutational burden (TMB) significantly improve outcomes. Specifically, patients with a high TMB showed prolonged progression-free survival (PFS) and overall survival (OS) compared to those with lower TMB levels. The combined presence of high PD-L1 and TMB was especially predictive of better performance, offering a median PFS of 28.47 months compared to significantly shorter times in other groups.<br /><br />The study also evaluated different treatment regimens. Dual checkpoint blockade (combining PD-(L)1 with CTLA-4 inhibitors) resulted in remarkably better median PFS and OS than PD-(L)1 monotherapy and combinations with chemotherapy. Specifically, dual ICI showed a median OS of 47.5 months compared to monotherapy's 14.7 months and ICI with chemotherapy's 18.9 months.<br /><br />These results highlight the potential of personalized ICI treatments, emphasizing that high PD-L1, very high TMB, and dual blockade therapy are beneficial for this specific NSCLC population. By identifying such predictive biomarkers, the study helps tailor therapeutic strategies for improved patient management among non-smokers with driver-negative NSCLC.<br /><br />Overall, the findings underscore the critical role of PD-L1 levels and TMB in guiding the use of ICIs, providing a pathway for enhanced clinical outcomes in this previously less-studied patient subset.

Asset Subtitle

Eleonora Gariazzo

Keywords

PD-(L)1 blockade

metastatic NSCLC

non-smoker

oncogene drivers

immune checkpoint inhibitors

PD-L1 expression

tumor mutational burden

progression-free survival

dual checkpoint blockade

personalized ICI treatments