Advancing immunotherapy in small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is a rapidly progressive neuroendocrine carcinoma that, until recently, had a very small armamentarium of effective treatments. Advances in DNA sequencing and whole transcriptomics have delineated key subtypes; therefore, SCLC is no longer viewed as a homogeneous cancer. Chemoimmunotherapy with PD1 blockade is now the standard of care for advanced disease, and ongoing research efforts are moving this strategy into the limited stage setting. Combination strategies of immunotherapy with radiation are also under active clinical trial in both limited and extensive stage disease.Plain Language Summary Small cell lung cancer (SCLC) is a rapidly progressive neuroendocrine carcinoma that, until recently, had a very small armamentarium of effective treatments. Chemoimmunotherapy with immune check point inhibitors is now the standard of care for advanced disease. This comprehensive review provides an overview of current treatment strategies for SCLC, unmet needs in this patient population, and emerging treatment strategies incorporating immunotherapy that will hopefully further improve outcomes for patients.

Small-Cell Lung Cancer: Is Liquid Biopsy a New Tool Able to Predict the Efficacy of Immunotherapy?

“…Other roles of EVs are closely connected to their cargo; in fact, these, by transporting miRNAs, can influence the cellular processes of target cells [70,73] or can themselves be nanodevices for the transport of drugs [74]. Clinical treatment failure of SCLC is a hot topic, and the investigation of mechanisms responsible for the acquisition of resistance to chemotherapy and immune therapy is essential to try to overcome it [7,75]. After surgical resection, the most effective therapy for SCLC is considered DDP-based chemotherapy (cis-diamminedichloroplatinum); however, the resistance, acquired or intrinsic, to this therapeutic approach affects patient response, resulting in a median survival time of only 4-5 months after chemotherapy.…”

“…The phase III IMpower133 trial firstly described a statistically significant overall survival (OS) benefit by adding atezolizumab, an anti-PD-L1, to carboplatin plus etoposide CT [3,5]. Subsequently, the phase III Caspian trial, evaluating first-line anti-PD-L1 durvalumab in combination with etoposide plus either cisplatin or carboplatin, confirmed a significant improvement in OS [6,7]. Both these ICIs have been approved in clinical practice.…”

Influence of treatment-related lymphopenia on the efficacy of immune checkpoint inhibitors in lung cancer: a meta-analysis

“…Recent evidence has emphasized the significant role of immune checkpoint inhibitors (ICIs) as efficacious anticancer agents through the inhibition of programmed death-ligand 1 (PD-L1), programmed death 1 (PD-1), or cytotoxic t-lymphocyte-associated protein 4 (CTLA-4) receptors, thereby augmenting the cytotoxicity of T lymphocytes towards tumor cells (7). The overall effectiveness and safety of immunotherapy utilizing ICIs have been generally demonstrated in patients afflicted with metastatic and locally advanced non-small cell lung cancer (NSCLC) (8), as well as small cell lung cancer (SCLC) (9). However, subsequent observations suggest that the therapeutic response to ICIs may vary in individual patients with lung cancer (10).…”