Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). While rapid progression (RP) has been proposed as a non-negligible pattern of response to ICIs, its definition and related factors remain unclear. This study aimed to develop a clinical definition of RP and to identify related factors. Methods: We retrospectively evaluated Chinese patients who had received an ICI as second-line or later treatment for locally advanced or metastatic NSCLC at a single center. We defined RP as radiological progression at the first response assessment (<2 months after starting the ICI), as well as confirmation of progressive disease or cancer-related death occurring at <3 months. The clinical outcomes were compared for patients with RP or non-RP to identify prognostic factors. Results: The study evaluated 74 eligible patients with detailed records regarding their ICI therapy, including 25 patients (33.8%) who had experienced RP. Relative to patients with non-RP, patients with RP had significantly shorter median progression-free survival (1.7 months [95% CI: 1.4-2.0 months] vs. 6.3 months [95% CI 5.2-7.3 months], P < 0.001; hazard ratio: 0.14, 95% CI: 0.08-0.25) and significantly shorter median overall survival (8.2 months [95% CI 3.0-13.4 months] vs. 22.6 months [95% CI 17.0-28.1 months], P < 0.001; hazard ratio: 0.27, 95% CI: 0.15-0.49). Multivariate analysis revealed that RP was independently predicted by the presence of ≥3 metastatic sites (P = 0.039) and a neutrophil-to-lymphocyte ratio of ≥3 (P = 0.044). Conclusions: Among NSCLC patients, RP was a common response to ICI monotherapy and was associated with dramatically reduced progression-free and overall survival. Care is needed when selecting ICI monotherapy for these patients, especially if they have ≥3 metastatic sites or a neutrophil-to-lymphocyte ratio of ≥3. Key pointsSignificant findings of the study: Patients with rapid progression after immune checkpoint inhibitor monotherapy had poor survival outcomes. The number of metastatic sites and the neutrophil-to-lymphocyte ratio may independently predict treatment response in this setting.What this study adds: This is the first study to evaluate rapid progression after second-line or later single-agent immunotherapy in a Chinese population. Our findings may help establish effective immunotherapy strategies for NSCLC.
respectively. The primary endpoints were progression free survival] (PFS) and pattern of failure, while the second endpoints were overall survival time (OS) and adverse events (AEs). Result: 36 patients were recruited in this study. The follow-up time was 14.5 months (range 3.4-30.4). Median age was 66 years (range 49-83). There were 20 males and 16 females. Eighteen patients with 19-del mutation and 18 had L858R mutation. Overall, median PFS and median OS was 14.1 months and 26.3 months (Figure 1), respectively. Three patients had progression at the primary site, 5 patients had mixed progression and 19 patients with distant progression only. In subgroup analysis, the median PFS was 14.1 months vs. 12.8 months in 19-del vs. L858R mutation patients. The median OS was 19.4 months in L858R mutation group while that in 19-del mutation was immature. Additionally, there was no grade 3 AEs in patients treated with this regimen. Conclusion:This study suggested that early primary tumor SBRT may play a role to delay resistance of first-line EGFR-TKI in advanced EGFRm NSCLC patients. Patients with 19-del mutation may gain a better survival time compared with L858R mutation. The promising results are to be validated in a multi-center, comparable randomized phase III clinical trial (Target-SBRT, NCT03727867).
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