Clinical cases of pembrolisumab immunotherapy treatment in patients with non-small lung cancer with high level of PD-L1 expression in fist line therapy

Abstract

In Russian Federation, lung cancer is the most frequently diagnosed malignant tumor among men and the fourth in the structure of morbidity among women, also occupying a leading position in the structure of mortality [1]. Non-small cell cancer (NSCLC) accounts for about 80 % of all lung tumors. In turn, in the structure of NSCLC, the most common types are adenocarcinoma (50 %) and squamous cell lung cancer (30 %). The appearance of drugs based on blocking immune checkpoints, in particular PD-1 and PD-L1, has changed the approach to the treatment of NSCLC. Currently, the determination of the optimal tactics for treatment tumors without activated mutations is based on predicting the sensitivity of the tumor to immunotherapy. Evaluation of PD-L1 expression makes it possible to divide patients with NSCLC into several groups of the level of sensitivity to modern immune checkpoint inhibitors. Thus, three groups are distinguished: with negative (≤ 1 %), intermediate (1–49 %) and high (≥ 50 %) expression of PD-L1. The latter includes 23–28 % of patients with advanced NSCLC, regardless of the histological form of the tumor [3]. There are also reasons to believe that in the near future a subgroup of patients with ultra-high expression (> 75 %) PD-L1 will be identifid, in which it is expected to achieve the maximum advantage from treatment with monoimmunotherapy. Pembrolizumab was approved for the treatment of advanced NSCLC with high level of PD-L1 expression (≥ 50 %) with the absence of EGFR / ALK mutations in the fist line of therapy following the publication of the results of the randomized phase III clinical trial KEYNOTE-024. In this study, the median overall survival in the pembrolizumab monotherapy arm was 30.0 months compared with 14.2 months with standard platinum-containing therapy [5]. These data formed the basis for the registration of the fist cytostatic-free regimen in patients with NSCLC without activating mutations. The subsequent study KEYNOTE-042 was an attempt to assess the effect of pembrolizumab in a wider group of patients – with a positive level of PD-L1 expression (PD-L1 ≥ 1 %; ≥ 20 %; ≥ 50 %). In general, the results of the study were positive, but many authors drew attention to the fact that the greatest effect of monoimmunotherapy with pembrolizumab is obtained by patients with a high level of PD-L1 expression. Median overall survival in this study was 20.0 months in the pembrolizumab group and 12.2 months in the chemotherapy group for all patients regardless of PD-L1 status. In this article two clinical cases of the use of the PD-L1 inhibitor pembrolizumab in patients with non-small cell lung cancer and high levels of PD-L1 expression are presented.