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. (August 2019)

• Record Type: Journal Article
• Authors: Lang, David; Horner, Andreas; Brehm, Elmar; Akbari, Kaveh; Hergan, Benedikt; Langer, Klaus; Asel, Christian; Scala, Mario; Kaiser, Bernhard; Lamprecht, Bernd
• Is Part Of: Lung cancer. Volume 134(2019)
• Page Start: 59
• Page End: 65
• Publication Date: 2019-08
• Subjects: Carcinoembryonic antigen -- CYFRA 21-1 -- RECIST -- Predictor -- Immunotherapy -- Biomarker; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.05.033
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: Serum tumor marker (STM) decrease at first restaging predicts superior PFS and OS STM increase ≥2-fold is associated with distinctly inferior response and survival Patients with SD/PD in initial CT restaging benefit when STM concomitantly decrease Multivariate predictors of survival: STM response, cerebral metastases, therapy line ≥3. 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.