Small-cell lung cancer (SCLC) is an aggressive disease with distinct pathological, clinical, and molecular characteristics from non–small-cell lung cancer. SCLC has high metastatic potential, resulting in a clinically poor prognosis. Early concurrent chemo-radiation is the standard of care for limited-stage SCLC (LS-SCLC). Prophylactic cranial irradiation (PCI) is recommended for patients with LS-SCLC without progression of disease after initial therapy. A combination of etoposide and cisplatin or carboplatin remains the mainstay of first-line treatment for ES-SCLC, with the addition of atezolizumab, now becoming standard. Most SCLCs initially respond to therapy but almost invariably recur. Topotecan and amrubicin (in Japan) remain the primary chemotherapy options for relapsed SCLC. Immunotherapy, including nivolumab with or without ipilimumab, is now available for refractory disease. In general, the poor prognosis of SCLC has not improved significantly for more than 3 decades. Recently, next-generation molecular profiling studies have identified new therapeutic targets for SCLC. A variety of proapoptotic agents, compounds capitalizing on DNA-repair defects, immunotherapy agents, and antibody–drug conjugates are being evaluated in SCLC, with a number of them showing early promise.
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