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.

Keywords: PARP inhibitors; extensive-stage small-cell lung cancer; immunotherapy; molecular subtypes; new evolving targeted agents; novel chemotherapy; small-molecule antiangiogenic drugs.