Abstract
Lung cancer is the second most common cancer in both sexes worldwide. Small-cell lung cancer (SCLC) is a form of neuroendocrine tumor, which is classified into limited and extensive-stage disease and shows excellent initial response to chemotherapy; however, almost all patients relapse later. During the past few years, several clinical trials have evaluated the effect of addition of immunotherapy to conventional chemotherapy in patients with extensive SCLC. Checkpoint inhibitors are currently under investigation, especially the CTLA-4 and PD-1/PD-L1 inhibitors. Nowadays, evidence show a statistically significant survival benefit of adding atezolizumab, an IgG1 monoclonal antibody targeting against PD-L1, to platinum-based chemotherapy plus etoposide in patients who have not received any previous systemic therapy. Furthermore, the role of nivolumab, an IgG4 anti-PD-1 monoclonal antibody, is significant for the treatment of relapsed SCLC cases. Recently, pembrolizumab was the first immunotherapeutic agent to be approved by the FDA for patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy and at least one other prior line of chemotherapy. Nevertheless, prognostic biomarkers to immunotherapy response remain to be discovered.
Highlights
Lung cancer is a major cause of morbidity and mortality worldwide
Ongoing NCT03066778 Ongoing NCT03043872 Ongoing NCT03033511 when it is combined with conventional chemotherapy is the fact that carboplatin and etoposide cannot deplete the intratumoral T cell population, which happen to be the targets of atezolizumab
Biomarkers. e fact that only a number of patients with ES Small-cell lung cancer (SCLC) show memorable response to specific targeted immunotherapy strategies has created the need for discovery of novel biomarkers in order to predict the population of patients most likely to benefit from them [31]. e predictive role of TMB to ICBs has been investigated in the “Checkmate 032” trial. e tumor mutational burden (TMB) is high in SCLC
Summary
Lung cancer is a major cause of morbidity and mortality worldwide. Nowadays, it is the second most common cancer in both men and women [1]. SCLC is categorized as neuroendocrine tumor (NET), and its subtypes include small-cell carcinoma and combined small-cell carcinoma (SCLC with a component of NSCLC) [4] It is frequently associated with paraneoplastic syndromes, such as syndrome of inappropriate antidiuretic hormone secretion, Lambert–Eaton myasthenic syndrome, hypercalcemia, and many others [3, 4]. E majority of SCLCs express alterations in chromosome 3p and mutations regarding the following genes: RB1, TP53, RASSF1, MYC, FGFR1, and PTEN [5, 6]. Except for these genomic alterations, there is malfunction of specific regulatory pathways
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