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Early serum tumor marker dynamics predict progression-free and overall survival in single PD-1/PD-L1 inhibitor treated advanced NSCLC-A retrospective cohort study.
Lung Cancer 2019; 134:59-65LC

Abstract

OBJECTIVES

To evaluate serum tumor markers (STM) as biomarkers for treatment monitoring and prognosis in advanced non-small cell lung cancer (NSCLC) treated with single-agent PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) therapy.

MATERIALS AND METHODS

Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cytokeratin-19 fragments (CYFRA 21-1) and neuron specific enolase (NSE) were routinely measured at NSCLC diagnosis, initially elevated markers were used for follow-up. Leading STM change between ICI initiation and first subsequent restaging as well as corresponding computed tomography evaluations according to response evaluation criteria in solid tumors (RECIST) were retrospectively analyzed regarding progression-free (PFS) and overall survival (OS). In uni- and multivariate stepwise Cox-regression analyses, STM and RECIST response were analyzed for their impact on PFS and OS together with other known prognostic patient and tumor characteristics.

RESULTS

Among 84 patients (61% men, mean age 68 years), median PFS was significantly (p < 0.001) longer, when STM decreased (11 M (7,19) N = 37) than in case of increases (<2-fold: 6 M (3,8) N = 31; ≥2-fold: 2 M (1,2) N = 16). Patients with initial STM decrease had longer (p < 0.001) median OS (not reached) than with STM increase (<2-fold: 14 M (12,26); ≥2-fold: 4 M (3,7)). Patients with stable or progressive disease by RECIST and concomitant STM decrease had longer (p < 0.001) PFS and OS (8 M (4,14) and 18 M (10,n.e.) N = 24) than upon STM increase (PFS: 2 M (2,4); OS: 10 M (6,13) N = 42). Significant impact on PFS was shown for STM response (p < 0.001), RECIST response (p = 0.003) and PD-L1 status (p = 0.003). For OS, STM response (p < 0.001), presence of cerebral metastases (p = 0.036) and therapy line ≥3 (p = 0.001) were identified.

CONCLUSION

Decreasing leading STM at first restaging predict longer PFS and OS and identify patients with favorable outcomes among initial radiological non-responders in ICI treated NSCLC patients.

Authors+Show Affiliations

Department of Pulmonology, Kepler University Hospital Krankenhausstrasse 9, 4020 Linz, Austria(1). Electronic address: david.lang@kepleruniklinikum.at.Department of Pulmonology, Kepler University Hospital Krankenhausstrasse 9, 4020 Linz, Austria(1).Department of Pulmonology, Kepler University Hospital Krankenhausstrasse 9, 4020 Linz, Austria(1).Central Radiology Institute, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria(2).Central Radiology Institute, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria(2).Central Radiology Institute, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria(2).Central Radiology Institute, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria(2).Central Radiology Institute, Kepler University Hospital, Krankenhausstrasse 9, 4020 Linz, Austria(2).Department of Pulmonology, Kepler University Hospital Krankenhausstrasse 9, 4020 Linz, Austria(1).Department of Pulmonology, Kepler University Hospital Krankenhausstrasse 9, 4020 Linz, Austria(1).

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31319996

Citation

Lang, David, et al. "Early Serum Tumor Marker Dynamics Predict Progression-free and Overall Survival in Single PD-1/PD-L1 Inhibitor Treated Advanced NSCLC-A Retrospective Cohort Study." Lung Cancer (Amsterdam, Netherlands), vol. 134, 2019, pp. 59-65.
Lang D, Horner A, Brehm E, et al. Early serum tumor marker dynamics predict progression-free and overall survival in single PD-1/PD-L1 inhibitor treated advanced NSCLC-A retrospective cohort study. Lung Cancer. 2019;134:59-65.
Lang, D., Horner, A., Brehm, E., Akbari, K., Hergan, B., Langer, K., ... Lamprecht, B. (2019). Early serum tumor marker dynamics predict progression-free and overall survival in single PD-1/PD-L1 inhibitor treated advanced NSCLC-A retrospective cohort study. Lung Cancer (Amsterdam, Netherlands), 134, pp. 59-65. doi:10.1016/j.lungcan.2019.05.033.
Lang D, et al. Early Serum Tumor Marker Dynamics Predict Progression-free and Overall Survival in Single PD-1/PD-L1 Inhibitor Treated Advanced NSCLC-A Retrospective Cohort Study. Lung Cancer. 2019;134:59-65. PubMed PMID: 31319996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early serum tumor marker dynamics predict progression-free and overall survival in single PD-1/PD-L1 inhibitor treated advanced NSCLC-A retrospective cohort study. AU - Lang,David, AU - Horner,Andreas, AU - Brehm,Elmar, AU - Akbari,Kaveh, AU - Hergan,Benedikt, AU - Langer,Klaus, AU - Asel,Christian, AU - Scala,Mario, AU - Kaiser,Bernhard, AU - Lamprecht,Bernd, Y1 - 2019/05/31/ PY - 2018/12/06/received PY - 2019/05/29/revised PY - 2019/05/30/accepted PY - 2019/7/20/entrez KW - Biomarker KW - CYFRA 21-1 KW - Carcinoembryonic antigen KW - Immunotherapy KW - Predictor KW - RECIST SP - 59 EP - 65 JF - Lung cancer (Amsterdam, Netherlands) JO - Lung Cancer VL - 134 N2 - OBJECTIVES: To evaluate serum tumor markers (STM) as biomarkers for treatment monitoring and prognosis in advanced non-small cell lung cancer (NSCLC) treated with single-agent PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: Carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), cytokeratin-19 fragments (CYFRA 21-1) and neuron specific enolase (NSE) were routinely measured at NSCLC diagnosis, initially elevated markers were used for follow-up. Leading STM change between ICI initiation and first subsequent restaging as well as corresponding computed tomography evaluations according to response evaluation criteria in solid tumors (RECIST) were retrospectively analyzed regarding progression-free (PFS) and overall survival (OS). In uni- and multivariate stepwise Cox-regression analyses, STM and RECIST response were analyzed for their impact on PFS and OS together with other known prognostic patient and tumor characteristics. RESULTS: Among 84 patients (61% men, mean age 68 years), median PFS was significantly (p < 0.001) longer, when STM decreased (11 M (7,19) N = 37) than in case of increases (<2-fold: 6 M (3,8) N = 31; ≥2-fold: 2 M (1,2) N = 16). Patients with initial STM decrease had longer (p < 0.001) median OS (not reached) than with STM increase (<2-fold: 14 M (12,26); ≥2-fold: 4 M (3,7)). Patients with stable or progressive disease by RECIST and concomitant STM decrease had longer (p < 0.001) PFS and OS (8 M (4,14) and 18 M (10,n.e.) N = 24) than upon STM increase (PFS: 2 M (2,4); OS: 10 M (6,13) N = 42). Significant impact on PFS was shown for STM response (p < 0.001), RECIST response (p = 0.003) and PD-L1 status (p = 0.003). For OS, STM response (p < 0.001), presence of cerebral metastases (p = 0.036) and therapy line ≥3 (p = 0.001) were identified. CONCLUSION: Decreasing leading STM at first restaging predict longer PFS and OS and identify patients with favorable outcomes among initial radiological non-responders in ICI treated NSCLC patients. SN - 1872-8332 UR - https://www.unboundmedicine.com/medline/citation/31319996/Early_serum_tumor_marker_dynamics_predict_progression-free_and_overall_survival_in_single_PD-1/PD-L1_inhibitor_treated_advanced_NSCLC-A_retrospective_cohort_study L2 - https://linkinghub.elsevier.com/retrieve/pii/S0169-5002(19)30488-X DB - PRIME DP - Unbound Medicine ER -