Factors related to rapid progression of non‐small cell lung cancer in Chinese patients treated using single‐agent immune checkpoint inhibitor treatment

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 points Significant 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.