Abstract:
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.
journal_name
Thorac Cancerjournal_title
Thoracic cancerauthors
Zhang L,Bai L,Liu X,Liu Y,Li S,Liu J,Zhang S,Yang C,Ren X,Cheng Ydoi
10.1111/1759-7714.13370subject
Has Abstractpub_date
2020-05-01 00:00:00pages
1170-1179issue
5eissn
1759-7706issn
1759-7714journal_volume
11pub_type
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