Extensive Stage Small Cell Lung Cancer and its Systemic Therapy Approaches

Abstract

ES-SCLC represents 60-80% of all SCLC cases. These tumors exhibits aggressive growth characteristics and an early propensity to metastasize, resulting in an unfavourable prognosis. The OS is limited to 9-12 months. Currently, systemic therapy is used as treatment, which has progressed from chemotherapy combinations ofplatinum+ etoposide to chemo immunotherapy.Optimal induction regimen is defined by recent studies such as IMpower133 and CASPIAN, recommending carboplatin/cisplatin plus etoposide with addition of PD-L1 inhibitors (atezolizumab or durvalumab). This combination leads to an increase in OS by 2-4 months and PFS benefit, with response rates ranging from 60-70%. Maintenance therapy has seen several improvements recently. Most notably, atezolizumab + lurbinectedin was approved by FDA in 2025 based on the results from IMforte trial which showed improvement in PFS by 46% and lower mortality risk by 27% compared to placebo, subsequently being granted NCCN category 2A recommendation as the preferred option following induction. Novel therapeutic avenues are being explored, such as tarlatamab, a bispecific antibody targeting DLL3, and multi-agent trials involving benmelstobart+ anlotinib or apatinib, both of which are anti-angiogenic agents, demonstrating encouraging results within biomarker-selected patient populations. Furthermore, consolidative thoracic radiotherapy, administered after chemoimmunotherapy or in conjunction with novel agents like Ifinatamab- deruxtecan (I-DXd), has shown objective response rates (ORR) of 55% and effective intracranial control. Future research will focus on combination intensification strategies, the utilization of liquid biopsies for resistance monitoring and clinical trials incorporating PARP inhibitors or antibody-drug conjugates (ADCs) to overcome the limitations of immunotherapy.