2/8/2024 0 Comments Keynote 158 trialThe standard chemotherapy regimen in this setting is cisplatin–etoposide. Chemotherapy can both augment the local efficacy of radiation and potentially treat micrometastatic disease. Local treatment options include surgery and radiotherapy. In non-metastatic SCLC, the therapeutic goals are to achieve durable control of thoracic disease and reduce the risk of metastatic dissemination. The initial approach to SCLC treatment varies substantially by stage. Although the tumor–node–metastasis (TNM) classification is preferred to the staging system of the Veterans Administration Lung Study Group (VALSG), which separates limited-stage (LS) disease (tumor confined to one hemi-thorax and one radiation port no malignant pleural or pericardial effusion) from extensive-stage (ES) disease (not meeting criteria for LS), the latest staging system is still widely used in both designing clinical trials and presenting data from them, as it effectively distinguishes patients treated primarily with chemotherapy (LS disease) from those treated with systemic chemotherapy or chemoimmunotherapy (ES disease). In these patients, systemic chemotherapy is typically the primary therapeutic modality, with some patients also drawing benefit from radiation therapy. Most patients have advanced disease and present with distant metastases, malignant effusions, and/or contralateral supraclavicular or hilar lymph node involvement. These two properties contribute to a particularly high mortality rate. In general, SCLC grows rapidly and has high metastatic potential. Small-cell lung cancer (SCLC) is a neuroendocrine tumor that represents about 13% of all lung cancers and occurs predominantly in smokers. With the therapeutic landscape for SCLC rapidly evolving, we review prior experience and future directions of pembrolizumab in ES-SCLC. In a recent clinical trial that included patients with previously untreated ES-SCLC, pembrolizumab in combination with platinum/etoposide met its progression-free survival endpoint, but overall survival (OS) did not cross the threshold for superiority. Food and Drug Administration (FDA) granting pembrolizumab accelerated approval as second- or third-line monotherapy for patients with extensive-stage (ES) SCLC. Prospective trials of pembrolizumab in patients with previously treated SCLC showed significant durability of responses. Pembrolizumab, a humanized IgG4 isotype antibody, targets the programmed cell death protein 1 (PD-1) pathway to restore anti-tumor immunity. The management of SCLC significantly changed for the first time in decades with the introduction of immune checkpoint inhibitors. Small-cell lung cancer (SCLC) is an aggressive subtype of lung cancer characterized by a rapid initial response and early development of resistance to systemic therapy and radiation.
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