Introduction

Lung cancer is the leading cause of cancer death worldwide [1], with non-small-cell lung cancer (NSCLC) accounting for approximately 85% of lung cancers. Recently, immunotherapy has represented a breakthrough in oncology, especially in its promise to treat a broad range of advanced cancer types, including NSCLC [2]. Human immune checkpoint inhibitor antibodies inhibit the programmed death (PD-1) receptor or its ligand PD-L1 and thus restore an efficient antitumour T cell response.
Despite advances in the therapeutic landscape of advanced NSCLC without targetable oncogenic driver alterations regarding immunotherapy, the indication spectrum of these new treatments as monotherapy still includes a minority of patients, whereas the vast majority are inevitably candidates for chemotherapy [3, 4]. In the phase II/III KEYNOTE-010 study, pembrolizumab significantly prolonged overall survival (OS) over docetaxel as second-line therapy in advanced NSCLC [5]. Despite these advances in treatment and the increased knowledge of the molecular pathways, there are still challenges in the identification of those patients who are most likely to benefit and those who will not [6, 7]. Durable responses can be observed in some populations, although the percentage has often been found to be approximately 20% [8, 9].
Overexpression of PD-L1 is an important and widely explored predictive biomarker for the response to anti-PD-1/PD-L1 antibodies [10]. Previous studies have demonstrated that the tumor microenvironment, with its most important players being neutrophils, platelets, macrophages and regulatory T cells, plays an essential regulatory role in cancer progression, metastasis and outcome [11, 12]. The results from recent studies suggest that a high neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) may predict a poor response to immune checkpoint inhibitors (ICIs) and poor outcome in patients with NSCLC [13-15]. A recent study proposed that the development of sarcopenia (low muscle mass), measured by the change in the psoas major muscle area (PMMA) at the L3 position, is a negative indicator for the ICI response [16]. In addition to poor responses, immunotherapy was also associated with rapid disease progression, i.e., hyperprogressive disease (HPD), in subpopulations of patients [17] with different incidences [18]. Unfortunately, currently, there are no biomarkers that predict the development of this life-threatening condition.
The purpose of this retrospective study was to evaluate the incidence of HPD after treatment with pembrolizumab as a second-line treatment in metastatic NSCLC patients and to search for indicators that are associated with the development of HPD.