Does early versus late initiation of immunotherapy in extensive-stage small cell lung cancer affect survival outcomes?

Abstract

8099 Background: Small cell lung cancer (SCLC) is an aggressive malignancy characterized by a rapid doubling time, high metastatic potential, and risk for relapse, prompting urgent treatment. Chemoimmunotherapy is the standard of care for first line treatment of extensive-stage SCLC (ES-SCLC). A study evaluating the National Cancer Database reported improvement in overall survival (OS) with initiation of chemotherapy after 28 days from a SCLC diagnosis. However, the optimal timing for initiation of immunotherapy for SCLC remains unclear. Here, we seek to understand if the timing of immunotherapy impacts outcomes for ES-SCLC. Methods: We retrospectively reviewed 149 charts of patients diagnosed with ES-SCLC treated at Indiana University (IU) Health and IU Simon Comprehensive Cancer Center from January 2018 to August 2024. Patients who received platinum-based chemotherapy combined with immune checkpoint inhibitor (ICI) as first line therapy were included. Patients were categorized into two groups based on ICI timing: (1) with the first cycle and (2) after the first cycle of chemotherapy. Additionally, patients were stratified by time-to-ICI-initiation from diagnosis (TII), ≤21 days vs >21 days. Results: A total of 75 patients diagnosed with ES-SCLC who received chemotherapy with either durvalumab (18.7%) or atezolizumab (81.3%) were identified. Across the entire cohort, median OS and progression-free survival (PFS) were 12.2 and 5 months, respectively. Patients with TII of ≤21 days had a median OS of 16.8 months, compared to 11.8 months for those with TII >21 days ( P = .26). Median OS was 16 months for patients who received ICI with the first cycle of chemotherapy and 10 months for those who received it later ( P = .43). Median PFS was similar between these groups. For univariate analysis, we used median OS for the entire cohort (i.e., 12.2 months) to define responders (OS ≥12.2 months, n=30) and non-responders (OS <12.2 months, n=42). In responders group, 60% received ICI with the first cycle of chemotherapy, compared to 53.3% in non-responders ( P = .57). Conclusions: The timing of initiation of immunotherapy, either with first cycle of chemotherapy or within 21 days of diagnosis, does not significantly improve outcomes in patients diagnosed with ES-SCLC. At our institution, atezolizumab is more commonly utilized for ES-SCLC. Recent real-world data suggests a survival benefit with use of durvalumab. Further prospective investigation is warranted to understand if ICI selection and timing can impact outcomes in ES-SCLC. Patients’ clinical and demographic characteristics. Variable Receipt of ICI with Cycle 1 P Value OverallN=75 No N=33 Yes N=42 Age 62.7 ± 9 61.5 ± 9.1 63.6 ± 8.9 0.299 ECOG PS ≥ 2 17 (25%) 9 (30%) 8 (21.1%) 0.679 Female 48 (64%) 22 (66.7%) 26 (61.9%) 0.670 Active tobacco use 43 (57.3%) 25 (75.8%) 18 (42.9%) 0.007 Presence of brain metastases 19 (25.3%) 6 (18.2%) 13 (31%) 0.207