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.