Clinical predictors of response to immunotherapy in patients with extensive-stage small cell lung cancer.

Abstract

e20125 Background: The addition of immunotherapy represents a significant breakthrough in the treatment paradigm of extensive-stage small cell lung cancer (ES-SCLC). Subgroup analyses highlight certain prognostic factors (i.e., performance status, cisplatin use, and the absence of brain metastases at diagnosis) associate with longer survival in SCLC. However, little is known related to clinical biomarkers to predict response to immunotherapy. Here, we inquire if certain SCLC-related variables may impact outcomes in this setting. Methods: We retrospectively reviewed charts of 149 patients diagnosed with SCLC treated at Indiana University Health and IU Simon Cancer Center from January 2018 to August 2024. Patients diagnosed with ES-SCLC who ever received immune checkpoint inhibitor (ICI) (durvalumab, atezolizumab, pembrolizumab, ipilimumab, and/or nivolumab) were included. Patients were divided into two groups based on progression-free survival (PFS) with ICI use: <150 days (non-responders) and ≥150 days (responders). Univariate analysis was used to compare the demographics and pertinent malignancy- and therapy-related variables. Results: A total of 89 patients diagnosed with ES-SCLC with any ICI use were identified, with 57 patients (64%, non-responders) and 32 patients (36%, responders, Table 1). Multivariate analysis confirmed that a greater number of combined cycles ( P = .005) or the diagnosis of malignancy-related thromboembolism (VTE) (OR, 7.03; 95% CI, 0.99–49, P = .05) were associated with improved PFS. Univariate analysis revealed that responders received more combined chemotherapy plus ICI cycles (4 vs 3 cycles, P = .012). Syndrome of inappropriate antidiuretic hormone (SIADH), use of GCSF, or the presence of brain and/or liver metastases did not impact PFS with ICI use in SCLC. Similar maximum standard uptake values (max SUV) on baseline positron emission tomography (PET) scan were observed (16.5 vs. 14.7, P = .58). No difference in active tobacco use was observed between the groups. Conclusions: Many SCLC-related diagnoses failed to predict durable response to ICI. Patients who received 4 cycles of combined chemo-ICI for ES-SCLC had improved PFS, compared to those receiving fewer cycles. The diagnosis of malignancy-related VTE may be associated with improved PFS in this cohort. Additional understanding of clinical variables related to ICI response is needed. Patients’ characteristics by group. P -value Variable OverallN=89 Non-respondersN=57 RespondersN=32 Odds Ratio [95% Wald CI] History of VTE 8 (9%) 3 (5.3%) 5 (15.6%) 3.33 [0.741, 15] 0.117 ECOG PS 0 17 (25.4%) 10 (22.7%) 7 (30.4%) 2.28 [0.518, 9.989] 0.276 Presence of brain metastases 25 (28.1%) 17 (29.8%) 8 (25%) 0.78 [0.294, 2.092] 0.627 Cycles of concurrent chemo-ICI received 4 (3, 4) 3 (2, 4) 4 (3, 5) 1.58 [1.108, 2.245] 0.012 Current tobacco use 49 (55.1%) 31 (54.4%) 18 (56.3%) 1.35 [0.545, 3.362] 0.515