The following is a summary of “PD-1T TILs as a Predictive Biomarker for Clinical Benefit to PD-1 Blockade in Patients with Advanced NSCLC” published in the November 2022 issue of Clinical Cancer by Hummelink et al.
In non-small cell lung cancer (NSCLC), only a subset of patients is experiencing long-term therapeutic benefits from PD-1 inhibition, highlighting the need for predictive biomarkers. Recent work by their group has uncovered a pool of tumor-reactive tumor-infiltrating T lymphocytes (TILs), designated PD-1T TILs, that may be predictive of outcome in non-small cell lung cancer. In this study, researchers looked into PD-1T TILs as a potential biomarker for non-small cell lung cancer. In 120 patients with advanced NSCLC who were treated with PD-1 inhibition, PD-1T TILs were digitally quantified from baseline samples. The primary endpoint was defined as the presence of disease control (DC) at the 6-month mark. Deaths at 12 months and overall survival were considered secondary outcomes.
The predictive utility of PD-1T TILs was investigated, taking into account factors such as lesion-specific responses, tissue sample characteristics, and the use of several biomarkers. The diagnostic performance of PD-1T TILs as a biomarker improved from 77% sensitivity and 67% specificity at 6 months to 93% sensitivity and 65% specificity at 12 months. In particular, a significant negative predictive value (NPV; 88% at 6 months, 98% at 12 months) accurately identified a patient group without clinical benefit. Progression-free (HR 0.39, 95% CI, 0.24-0.63, P<0.0001) and overall (HR 0.46, 95% CI, 0.28-0.76, P <0.01) survival was considerably prolonged in patients with high PD-1T TILs.
Analysis of lesion-specific responses and pre-treatment samples improved predictive performance. Notably, in the same group, PD-1T TILs had a better predictive performance than PD-L1 and tertiary lymphoid structures. The results of this study confirm that PD-1T TILs are a reliable biomarker for predicting which patients with advanced NSCLC may benefit from treatment with PD-1 blocking. Most significantly, the high NPV indicates that a group of patients who will not benefit from the intervention has been correctly identified.