Aim: To investigate potential association between administration of corticosteroids, antibiotics, probiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAID), statins and metformin and outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Patients and Methods: A total of 224 patients with advanced NSCLC treated at nine comprehensive cancer centers were analyzed in this national retrospective study. Survival statistics were evaluated using Kaplan-Meier method and Cox analysis. Results: Only corticosteroid use had a significant negative effect on the objective response rate. In the univariate analysis, there was no significant effect of the studied concomitant medications on the efficacy of nivolumab. In a subsequent multifactorial analysis, a possible positive effect of the concomitant use of NSAID at the initiation of nivolumab treatment was revealed. Conclusion: The results of the present retrospective exploratory analysis underscore the importance of knowing the exact type of concomitant medication, the route of administration, the dose of medication, and the region of the ongoing study. The present data indicated a significantly higher rate of progression in patients treated with corticosteroids and the possible positive effect of NSAID use at the initiation of nivolumab treatment.Nivolumab is a human monoclonal antibody to programmed cell death protein 1 (PD1) that represents a new therapeutic option in the second-line treatment of advanced non-smallcell lung cancer (NSCLC). Improved efficacy with a more favorable adverse event profile has been documented for nivolumab compared to docetaxel in phase III trials. However, the objective response rate of nivolumab monotherapy is only about 20%, with the disease control rate 2209

Aim: To investigate potential associations between clinical and standard peripheral blood biomarkers and clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Patients and Methods: A total of 120 patients with advanced NSCLC treated at seven comprehensive cancer care centers were analyzed in this national retrospective study. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. Results: Among clinical parameters, histology was significantly associated with progression-free survival. Univariate Cox-proportional hazards model indicated prognostic and predictive role of a panel of laboratory parameters reflecting chronic inflammatory pattern (elevated neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein and decrease in hemoglobin and albumin). Higher serum calcium concentration was also associated with nivolumab treatment effect. Conclusion: Tumor histology was the only clinical parameter predicting the outcome of nivolumab treatment.Among the laboratory parameters, our analysis identified a laboratory panel reflecting chronic inflammation as a potential predictive marker of nivolumab treatment.Nivolumab is a human monoclonal anti-programed cell death 1 (PD-1) therapy that represents a new therapeutic option in the second-line treatment of advanced non-small cell lung cancer (NSCLC). Improved efficacy and a more favorable adverse event profile have been documented for nivolumab compared to docetaxel in phase III studies. However, the objective response rate on nivolumab monotherapy is only about 20%, with the disease control rate reaching approximately 50% (1, 2). Therefore, many patients do not benefit from nivolumab treatment and, taking into account the cost/efficacy ratio, identification of predictive parameters that would aid identification of the most suitable candidates for this therapy remains a topic of high unmet medical need. Much effort has been made to demonstrate that programmed death-ligand 1 (PD-L1) expression on tumor cells represent, a potential biomarker of response to anti-PD1 therapy (3, 4). However, for nivolumab, this seems to hold true in nonsquamous NSCLC only, although data for other drugs, e.g. pembrolizumab, have demonstrated the predictive role of PD-L1 expression even in patients with squamous histology (5). For various reasons, PD-L1 expression is still not an ideal biomarker (6). Therefore, the search for other predictive biomarkers should continue. Several approaches 6771

Pemetrexed is an antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of locally advanced or metastatic stage non-small cell lung cancer. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of thyroid transcription factor 1 expression with outcome of a large cohort of patients with non-squamous non-small cell lung cancer treated with pemetrexed. We retrospectively analysed clinical data of 463 patients with advanced-stage non-small cell lung cancer (IIIB or IV) treated with pemetrexed-based chemotherapy. Thyroid transcription factor 1 expression was assessed using indirect immunohistochemical detection in formalin-fixed paraffin-embedded tumour tissue at the time of diagnosis. Thyroid transcription factor 1 expression was detected in the tumour tissue from 76.0% of patients, and tumours from 24.0% of patients were thyroid transcription factor 1 negative. The median progression-free survival and overall survival for patients with thyroid transcription factor 1 positive tumours were 4.8 and 11.8 months compared to 2.8 and 8.3 months for those with thyroid transcription factor 1 negative tumours (p = 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that thyroid transcription factor 1 expression was significantly associated with progression-free survival (hazard ratio = 1.57, p < 0.001) and also with overall survival (hazard ratio = 1.73, p < 0.001). In conclusion, the results of the conducted retrospective study suggest that the thyroid transcription factor 1 expression was independently associated with progression-free survival and overall survival in patients with advanced-stage nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.

Aim: To investigate potential associations between selected oncomarkers [carcinoembryonic antigen (CEA), CYFRA), and squamous cell carcinoma antigen (SCC)] and outcomes in patients with NSCLC treated with bevacizumab plus chemotherapy. Patients and Methods: We retrospectively analysed 105 patients with NSCLC from the Czech TULUNG registry treated at University Hospital in Pilsen with bevacizumab plus chemotherapy. Response to therapy was tested by Fisher's exact test. Survival statistics were evaluated using the Kaplan-Meier method and Cox analysis. Results: Only normal values of CYFRA (not CEA or SCC) were associated with significantly better overall and progression-free survival in univariate analysis. We also observed a trend for a better disease control rate in patients with normal levels of CYFRA. In a multivariate Cox model, only CYFRA was associated with significantly better overall but not progression-free survival. Conclusion: In our retrospective study, we point out the possibility of using CYFRA as a prognostic marker in patients with NSCLC treated with chemotherapy plus bevacizumab.

No abstract