P3.02c-087 The Relationship of TILs and PD-L1 Expression in NSCLC Adenocarcinoma in Little to Non-Smokers with Driver Mutations and Outcome Parameters

Abstract

Background: Culminating evidence shows the importance of the immune response in NSCLC and other cancer types. TILs seem to be a marker of good prognosis in many different tumor types, including NSCLC. The prognostic importance of PD-L1 expression in NSCLC remains less clear. This study will contribute more information to this topic in NSCLC and will verify the influence of driver mutations on TILs levels and PD-L1 expression. In addition, the predictive role of TILs and PD-L1 expression in EGFR mutants, who received erlotinib, will be evaluated. Methods: Clinical data, genetic analysis and tumor biopsies of the FIELT-1 cohort (stage IIIb or IV NSCLC patients with little or non-smoking history) were retrospectively evaluated. PD-L1 expression was evaluated with a PD-1/PD-L1 IHC double staining. TILs were evaluated on H&E slides, using the method developed by an international working group under direction of R. Salgado. Results: Measuring stromal TILs on H&E slides proved to be reproducible (ICC=0.74). The measurement of intratumor TILs (ICC=0.16) did not reach the cut-off ICC of 0.70. There was no difference in stromal TILs counts in KRAS (p=0.454) and EGFR (p=0.962) mutant tumors compared to their respective wild type tumors, nor was there any difference in sTILs counts between KRAS and EGFR mutants (p=0.605). The median OS in the general population was 49 weeks. There was a significant difference in median OS between the stromal TILs high tumors and the stromal TILs low tumors (68 weeks vs. 35 weeks respectively; p=0.003). A similar observation was made in the KRAS mutant tumors (95 weeks vs. 12 weeks; p=0.003). In the EGFR mutants no significant difference in median OS could be found according to the stromal TILs counts (p=0.65). There was no difference in the stromal TILs counts of EGFR mutants who responded (p=0.160) or showed clinical benefit (p=0.621) after receiving erlotinib, compared to those who did not. The analysis of the PD-1/PD-L1 double staining has been postponed. Results will be available by the end of August 2016. Conclusion: The results of the current study reinforce the prognostic role of TILs in NSCLC. Furthermore, this is the first study to confirm that the used scoring method on H&E slides is reproducible in NSCLC. This study is also the first to report about the relation between driver mutation and TILs, with results suggesting that the immune system plays a more crucial role in KRAS mutants than in EGFR mutants.