Journal Article Epublish
PubMed: 40240475 DOI: 10.1038/s41598-025-97792-9
Low serum neopterin early indicates durable benefits of atezolizumab and pembrolizumab therapy in advanced lung cancer.
Sci Rep 15(1):13078
Authors: Anna Siemiątkowska, Barbara Kuźnar-Kamińska, Maciej Bryl, Katarzyna Kosicka-Noworzyń, Paulina Przybył, Iwona Gołda-Gocka, Franciszek K Główka
Affiliations
- Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806, Poznań, Poland.
- Department of Pulmonology, Allergology and Respiratory Oncology, Poznan University of Medical Sciences, 84 Szamarzewskiego Street, 60-569, Poznań, Poland.
- Department of Clinical Oncology with the Subdepartment of Diurnal Chemotherapy, Wielkopolska Center of Pulmonology and Thoracic Surgery, 62 Szamarzewskiego Street, 60-569, Poznań, Poland.
- Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806, Poznań, Poland.
Abstract
Cancer is a state of immunological imbalance associated with chronic inflammation and local immunosuppression. Introducing immune checkpoint inhibitors was a breakthrough in cancer treatment. However, the treatment outcomes remain unsatisfactory, and many patients still progress after the initial response. The study aimed to assess whether serum neopterin (NEO), an indicator of cellular immune activation, could be used as a predictor of the long-term benefits of drugs blocking the programmed cell death protein 1 pathway (anti-PD-1/PD-L1 drugs). We enrolled 103 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1/PD-L1s. Serum was collected at baseline and at the end of each treatment cycle for the first three months of immunotherapy. NEO concentrations were determined with a validated high-performance liquid chromatography assay and correlated with treatment outcomes. Low-NEO status (i.e., serum NEO levels ≤ 71.65 nM at the end of the 3rd treatment cycle and ≤ 66.84 nM at the end of the 4th treatment cycle) increased the odds of ≥ 12-month benefits (odds ratio, OR = 11.70, p < 0.001), and decreased the hazard of NSCLC progression (hazard ratio, HR = 0.327, p < 0.001) and treatment failure (adjusted HR = 0.450, p < 0.05). Patients with low-NEO status had three times longer progression-free survival (PFS, 17.3 vs. 5.9 months) and three times longer time to treatment failure (TTF, 16.3 vs. 5.5 months) compared to other patients. Baseline NEO levels could not discriminate between patients who had and lacked the long-term benefits of treatment. In conclusion, the on-treatment serum NEO concentrations could be a biomarker of the long-term benefits of the anti-PD-1/PD-L1 treatment in advanced NSCLC.
MeSH
Cells, Lung, Serum, Pharmaceutical Preparations, Neoplasms, Carcinoma, Non-Small-Cell Lung, Treatment Failure, Lung Neoplasms, Therapeutics, Neopterin