Authors: Tong Chen, Mingzhao Wang, Yanchao Chen, Yang Cao, Yutao Liu
Published: 2024-06-14
DOI: 10.1200/jco.2024.42.16_suppl.e20125
Source: Full article
e20125 Background: Small cell lung cancer (SCLC) is an highly aggressive malignancy with a poor prognosis, and current therapeutic options for relapsed SCLC are limited. This study aims to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with antiangiogenic agents in patients (pts) with previously treated SCLC, and to initially explore biomarkers for the response prediction of combination therapy. Methods: In this single-center study, medical records and follow-up data of pts with SCLC who received antiangiogenic therapy plus immunotherapy (combination therapy) or antiangiogenic monotherapy as second or later-line treatment were retrospectively analyzed. The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Additionally, plasma was collected from pts in the combination therapy cohort before and after two cycles of treatment. The samples were tested for extracellular vesicles (EVs) membrane protein expression profiles. Potential biomarkers for the therapeutic effect were screened and then evaluated for their predictive performance. Results: A total of 61 pts were enrolled, including the combination therapy group (n = 40) and the antiangiogenic monotherapy group (n = 21). Baseline characteristics of the two groups were comparable. Kaplan-Meier (K-M) curve demonstrated superior PFS in combination therapy group than in monotherapy group (mPFS: 4.0 vs.2.7 months, P = 0.029). Both univariate (HR 0.634, 95%CI: 0.420-0.959, P = 0.031) and multivariate Cox regression (HR 0.554, 95%CI: 0.345-0.888, P = 0.014) proved that combination therapy, compared to antiangiogenic monotherapy, was correlated with markedly improved PFS. The combination group had higher DCR than the monotherapy group (77.5% vs. 52.4%, P = 0.044). No significant difference in the incidence of AEs between the two groups was observed. Plasma EV membrane protein detection and differential expression analysis suggested that IL-12 served as a prognostic marker for adverse outcomes in combination therapy. The Receiver Operating Characteristic (ROC) curve and K-M curve showed that IL-12 possessed favorable efficacy prediction performance (Area Under Curve, AUC = 0.85), and pts with high IL-12 expression exhibited significantly shorter PFS in contrast to those with low expression (P < 0.0001). In pts experiencing progression within 3 months, higher levels of IL-12 were detected compared to those who did not (P = 0.002). Conclusions: ICIs plus antiangiogenic therapy has demonstrated superior efficacy in disease control and delayed progression over antiangiogenic monotherapy as later-line treatment in pts with SCLC. Serum EV membrane proteins showed promising predictive value for the efficacy of combination therapy.