Immune checkpoint inhibitors in the driver’s seat: Evaluating the evolving evidence in the treatment of extensive-stage small-cell lung cancer

Abstract

Until recently, improving treatment-related outcomes remained an unmet medical need for patients with extensive-stage small-cell lung cancer (ES-SCLC). Because of its rapid growth profile and tendency to metastasize early in the disease course, ES-SCLC accounts for approximately two-thirds of all SCLC diagnoses. Although treatment-naive ES-SCLC is highly responsive to initial therapy with a platinum compound in combination with etoposide (EP), most patients experience disease recurrence within six months, and fewer than 5% survive to five years. In the platinum resistant/refractory settings, there are no standard guidelines for treatment, with various studies showing similar response rates (RRs) and survival outcomes for different single agent chemotherapies.Immune checkpoint inhibitors (ICIs) have been shown to improve outcomes in patients with a range of tumor types, especially in those characterized by high tumor mutational burden (TMB). The success of studies evaluating ICIs in multiple treatment settings and tumors, including SCLC, has led to trials assessing their role in ES-SCLC. Results from these trials suggest that this modality can improve outcomes, including in the first-line setting. Recent data show improved survival for patients with treatment-naive ES-SCLC who received an ICI in combination with standard chemotherapy. Multiple trials evaluating a potential role for ICIs in the first-line setting are currently ongoing, with results expected within the next year.This paper incorporates clinical trial data and current guideline recommendations to show current evidence related to clinical decision making and patient management for those receiving ICI-containing regimens as first-line therapy for ES-SCLC.