Aktuelle Standards und vielversprechende Innovationen in der medikamentösen Zweitlinientherapie des metastasierten kleinzelligen Lungenkarzinoms (ED-SCLC)

The combination of a PD-L1-targeted checkpoint inhibitor with platinum and etoposide chemotherapy is the standard of care in first-line palliative treatment of extended-disease small cell lung cancer (ED-SCLC), with a median overall survival of approximately 13 months. Following failure of chemoimmunotherapy, the DNA topoisomerase I inhibitor topotecan is an approved therapeutic option. Topotecan has demonstrated an extension in median overall survival from about 3.2 to 6 months, with a prolonged maintenance of quality of life compared to best supportive care. Additional chemotherapeutic agents with proven efficacy include irinotecan, paclitaxel, ifosfamide, anthracyclines, and lurbinectedin. Tarlatamab is a bispecific fusion protein that induces immune-mediated destruction of DLL-3-positive tumor cells by binding to the notch ligand delta like ligand 3 (DLL-3) and the T-cell antigen CD3. In a phase II study involving 220 heavily pretreated ED-SCLC patients, tarlatamab demonstrated an objective response rate of 40%, a median progression-free survival of 5 months, and a median overall survival of 14 months. Based on these data, the United States Food and Drug Administration (FDA) has granted accelerated approval for the treatment of adult patients with ED-SCLC with disease progression on or after platinum-based chemotherapy. Tarlatamab is currently being evaluated in global phase III trials for both first- and second-line settings. Other biotherapeutics with similar mechanism of action (e.g., BI 764532, HPN328) are also under clinical investigation. Additionally, various antibody–drug conjugates are being tested for the treatment of SCLC. There is hope that these innovations will significantly advance treatment options and outcomes for patients with ED-SCLC.