Extensive‐stage small‐cell lung cancer: Current management and future directions

Abstract

Extensive-stage small-cell lung cancer (ES-SCLC) is regarded as a refractory carcinoma associated with extremely rapid disease progression. After more than three decades without clinical advances, research on immune checkpoint inhibitors (ICIs) combined with platinum-based chemotherapy has led to the first treatment breakthrough, establishing a new standard for the first-line treatment of ES-SCLC. Further studies have extensively evaluated small-molecule antiangiogenic drugs, PARP inhibitors, as well as lurbinectedin in SCLC and have demonstrated some benefit, although no breakthroughs have been made. In addition, newer therapeutic strategies with targeted agents, novel chemotherapeutics and immunotherapies are evolving as they are being actively explored and hold promise for patients with this disease. Notably, the preliminary identification of SCLC molecular subtypes driven by the expression of dominant transcription factors with RNA sequencing profiles has made it possible to identify molecularly tailored therapeutic approaches, which increases the potential for individualized precision treatment of SCLC.In this review, we summarize recent research advances in ES-SCLC, outline the current management of this disease and reflect on directions for future development.

Patterns of treatment failure for PD-(L)1 refractory extensive-stage small cell lung cancer in continued PD-(L)1 treatment

“…Given the small sample size of this study, our conclusions need to be further validated in a larger cohort. To date, there has been no breakthrough in the search for effective biomarkers to select advantaged patients, and the initial framework for molecular subtypes of SCLC is not yet mature [27] . To clarify the dominant population of single immunotherapy and combined immunotherapy, the best opportunity for immunotherapy, and the ideal mode of combined therapy are urgent problems to be solved in the next research.…”

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies

“… 141 Over 60% of patients with SCLC are diagnosed with extensive-stage SCLC, facing a median survival of less than 10 months. 142 Even for those diagnosed with limited-stage SCLC, survival rates are generally poor. While initial responses to standard chemotherapy and radiotherapy are common, rapid relapse due to acquired chemotherapy resistance is a frequent challenge.…”

Immune activation effects at different irradiated sites and optimal timing of radioimmunotherapy in patients with extensive-stage small cell lung cancer: a real-world analysis

“…With the publication of results from the IMpower133, CASPIAN, ASTRUM-005, and CAPSTONE-1 studies, ICIs have been shown to greatly improve the survival of patients with ES-SCLC [42]. Although immunotherapy combined with chemotherapy (ICT) plays a signi cant role in ES-SCLC, data related to the combined e cacy and safety of RT is insu cient, and the results are controversial.…”