Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors
Abstract Background Non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitors show long lasting responses, but it is hard to predict which patients will profit from this treatment with the currently used marker, programmed death ligand 1 (PD-L1). We hypothesized that circulating...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2019-07-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40425-019-0649-2 |
| _version_ | 1818312350216749056 |
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| author | Menno Tamminga Sanne de Wit T. Jeroen N. Hiltermann Wim Timens Ed Schuuring Leon W. M. M. Terstappen Harry J. M. Groen |
| author_facet | Menno Tamminga Sanne de Wit T. Jeroen N. Hiltermann Wim Timens Ed Schuuring Leon W. M. M. Terstappen Harry J. M. Groen |
| author_sort | Menno Tamminga |
| collection | DOAJ |
| description | Abstract Background Non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitors show long lasting responses, but it is hard to predict which patients will profit from this treatment with the currently used marker, programmed death ligand 1 (PD-L1). We hypothesized that circulating tumor cells (CTC) or tumor derived extracellular vesicles (tdEV) are markers of treatment efficacy. Methods Patients with advanced NSCLC treated with checkpoint inhibitors were included. Blood was drawn at baseline (T0) and at 4 weeks of treatment (T1) for analysis of CTC and tdEV using CellSearch®. Tumor response was classified as partial or complete response based on the response evaluation criteria in solid tumors (RECISTv1.1) measured 4–6 weeks after start of treatment. Durable response was defined as stable disease, partial or complete response without disease progression at 6 months. Analyses were adjusted for covariables including PD-L1 expression. Results We included 104 patients (30 with a tumor response, 74 non-responders, 2 responses not evaluable due to early death); 63 patients provided T1 samples. All patients were treated with PD-L1 inhibitors. The majority of patients received second (85%) or third line (treatment with nivolumab monotherapy (89%). CTC were present in 33/104 patients at T0 (32%) and 17/63 at T1 (27%), 9/63 patients had CTC (14%) at both time points. The presence of CTC, both at T0 (OR = 0.28, p = 0.02,) and T1 (OR = 0.07, p < 0.01), was an independent predictive factor for a lack of durable response and was associated with worse progression free and overall survival. More tdEV were associated with shorter survival but not with response rate. Conclusion CTC occur in one third of advanced NSCLC patients and their presence is a predictive factor for a worse durable response rate to checkpoint inhibitors. tdEV are associated with shorter survival but not with response. |
| first_indexed | 2024-12-13T08:16:27Z |
| format | Article |
| id | doaj.art-9a8b54e897394e67804a2f24e72d16a9 |
| institution | Directory Open Access Journal |
| issn | 2051-1426 |
| language | English |
| last_indexed | 2024-12-13T08:16:27Z |
| publishDate | 2019-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj.art-9a8b54e897394e67804a2f24e72d16a92022-12-21T23:54:06ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262019-07-01711910.1186/s40425-019-0649-2Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitorsMenno Tamminga0Sanne de Wit1T. Jeroen N. Hiltermann2Wim Timens3Ed Schuuring4Leon W. M. M. Terstappen5Harry J. M. Groen6Department of Pulmonary Diseases, University of Groningen, University Medical Center GroningenDepartment of Medical Cell BioPhysics, Faculty of Sciences and Technology, University of TwenteDepartment of Pulmonary Diseases, University of Groningen, University Medical Center GroningenDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center GroningenDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center GroningenDepartment of Medical Cell BioPhysics, Faculty of Sciences and Technology, University of TwenteDepartment of Pulmonary Diseases, University of Groningen, University Medical Center GroningenAbstract Background Non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitors show long lasting responses, but it is hard to predict which patients will profit from this treatment with the currently used marker, programmed death ligand 1 (PD-L1). We hypothesized that circulating tumor cells (CTC) or tumor derived extracellular vesicles (tdEV) are markers of treatment efficacy. Methods Patients with advanced NSCLC treated with checkpoint inhibitors were included. Blood was drawn at baseline (T0) and at 4 weeks of treatment (T1) for analysis of CTC and tdEV using CellSearch®. Tumor response was classified as partial or complete response based on the response evaluation criteria in solid tumors (RECISTv1.1) measured 4–6 weeks after start of treatment. Durable response was defined as stable disease, partial or complete response without disease progression at 6 months. Analyses were adjusted for covariables including PD-L1 expression. Results We included 104 patients (30 with a tumor response, 74 non-responders, 2 responses not evaluable due to early death); 63 patients provided T1 samples. All patients were treated with PD-L1 inhibitors. The majority of patients received second (85%) or third line (treatment with nivolumab monotherapy (89%). CTC were present in 33/104 patients at T0 (32%) and 17/63 at T1 (27%), 9/63 patients had CTC (14%) at both time points. The presence of CTC, both at T0 (OR = 0.28, p = 0.02,) and T1 (OR = 0.07, p < 0.01), was an independent predictive factor for a lack of durable response and was associated with worse progression free and overall survival. More tdEV were associated with shorter survival but not with response rate. Conclusion CTC occur in one third of advanced NSCLC patients and their presence is a predictive factor for a worse durable response rate to checkpoint inhibitors. tdEV are associated with shorter survival but not with response.http://link.springer.com/article/10.1186/s40425-019-0649-2Circulating tumor cells (CTC)Non-small cell lung cancer (NSCLC)ImmunotherapyCheckpoint inhibitorsTumor derived extracellular vesicles (tdEV)Durable response |
| spellingShingle | Menno Tamminga Sanne de Wit T. Jeroen N. Hiltermann Wim Timens Ed Schuuring Leon W. M. M. Terstappen Harry J. M. Groen Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors Journal for ImmunoTherapy of Cancer Circulating tumor cells (CTC) Non-small cell lung cancer (NSCLC) Immunotherapy Checkpoint inhibitors Tumor derived extracellular vesicles (tdEV) Durable response |
| title | Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors |
| title_full | Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors |
| title_fullStr | Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors |
| title_full_unstemmed | Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors |
| title_short | Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors |
| title_sort | circulating tumor cells in advanced non small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors |
| topic | Circulating tumor cells (CTC) Non-small cell lung cancer (NSCLC) Immunotherapy Checkpoint inhibitors Tumor derived extracellular vesicles (tdEV) Durable response |
| url | http://link.springer.com/article/10.1186/s40425-019-0649-2 |
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