Abstract
Small cell lung cancer (SCLC) is a highly lethal disease, characterized by early metastasis and rapid growth, and no effective treatment after relapse. Etoposide-platinum (EP) combination has been the backbone therapy of SCLC over the past 30 years. It is extremely urgent and important to seek new therapies for SCLC. In the past 5 years, immunotherapy, such as immune checkpoint inhibitors programmed cell death protein-1 (PD-1), cytotoxic T lymphocyte associatedprotein-4 (CTLA-4), has made remarkable achievements in the treatment of patients with SCLC, and it has become the first-line option for the treatment of some patients. Some traditional chemotherapeutic drugs or targeted drugs, such as alkylating agent temozolomide and transcription inhibitor lurbinectedin, have been found to have immunomodulatory effects and are expected to become new immunotherapeutic agents. In this study, we aimed to review the efficacy of new treatments for SCLC and discuss the current challenges and application prospect in the treatment of SCLC patients.
Highlights
Small cell lung cancer (SCLC) is a poorly differentiated and high-grade neuroendocrine tumor, which accounts for 10%−15% of all lung cancers [1,2]
In a phase II study (TRINITY), the effects of rovalpituzumab tesirine (Rova-T) as first-line or secondline treatment in delta-like protein 3 (DLL3) positive (≥25% tumor cells expressing DLL3 by immunohistochemistry) SCLC patients were detected, the results showed that Rova-T was more effective in third-line treatment in patients with high expression of DLL3 (≥75%), but the objective response rate (ORR) is only 18% in the overall population [62]
In the IMpower133 study, atzolizumab combined with chemotherapy as first-line therapy showed improvement in overall survival (OS) [15]
Summary
Small cell lung cancer (SCLC) is a poorly differentiated and high-grade neuroendocrine tumor, which accounts for 10%−15% of all lung cancers [1,2]. SCLC is characterized by short tumor doubling time (TDT) and metastasis at an early stage. More than half of the patients were diagnosed at extensive disease (ED) [2,3]. Chemotherapy combined with chest radiotherapy has been considered as a standard treatment for SCLC patients for the past 50 years [4]. SCLC patients are still sensitive to current therapy, with an objective response rate (ORR) of 70%, quite a lot of patients develop drug resistance or disease relapse rapidly after remission [4]. The median overall survival (OS) is 15−20 months with limited disease (LD)SCLC and 8−13 months with ED-SCLC [3,5,6]
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