Prognostic role of serum C-reactive protein in patients with advanced-stage NSCLC treated with pemetrexed.

Pemetrexed is an intravenously administered antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of patients with advanced non-small cell lung cancer (NSCLC). It has been previously demonstrated that the superiority of pemetrexed is limited to patients with non-squamous histology. 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 baseline serum levels of C-reactive protein (CRP) with outcomes in a large cohort of patients with non-squamous NSCLC treated with pemetrexed. Clinical data of 325 patients were analysed. Serum samples were collected within one week before the initiation of treatment. The median progression-free (PFS) and overall survival (OS) for patients with high CRP was 2.1 and 9.5 compared to 4.2 and 20.5 months for those with normal CRP (p=0.002 and p<0.001, respectively). The multivariable Cox proportional hazards model revealed that serum CRP (HR=1.46, p=0.002) was significantly associated with PFS and also with OS (HR=1.95, p<0.001). In conclusion, the study results suggest that pretreatment serum CRP is associated with poor outcome of non-squamous NSCLC patients treated with pemetrexed.

[Immunotherapy in the Treatment of Lung Cancer]. / Imunoterapie v lécbe karcinomu plic.

BACKGROUND: Lung cancer occupies the leading position of cancer incidence and mortality worldwide, including in the Czech Republic. Despite significant advances in systemic oncology treatments, lung cancer still has the worst prognosis, which is driving the need for innovative therapies and methods to treat this disease. Immunotherapy is a developing area of systemic oncology treatment, which has recently begun to be significantly applied to patients with lung carcinoma. The most useful type of immunotherapy currently employs checkpoint inhibitors, including CTLA-4 inhibitors (ipilimumab and tremelimumab) and PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, durvalumab, and avelumab). Except for monotherapy, different combinations of these inhibitors or combinations between one more of these inhibitors and chemotherapy or targeted treatment are being actively studied. Despite intensive investigations, anti-tumor vaccines and cytokines have not had an important impact on the treatment of lung cancer. Checkpoint inhibitors have yielded favorable results, especially for the treatment of advanced (i.e., stage IIIB and IV) non-small cell lung cancer (NSCLC) and are being extensively investigated for the treatment of SCLC. AIM: The aim of this review was to summarize the most important achievements, possibilities, and perspectives of modern immunotherapy for the treatment of patients with lung cancer. CONCLUSION: Immunotherapy is an important tool in todays arsenal of oncology treatments, and for patients with lung cancer it offers the hope of prolonging life and img iprovints quality.Key words: immunotherapy - lung cancer - NSCLC - SCLC - checkpoint inhibitors This work was supported by National Sustainability Programme I No. LO1503 provided by Ministry of education, youth and sports and program No. 17-30748A devided by The Ministry of Health of the Czech Republic. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 31. 8. 2017Accepted: 7. 9. 2017.

Serum albumin is a strong predictor of survival in patients with advanced-stage non-small cell lung cancer treated with erlotinib.

Molecular targeted therapy based on tyrosine kinase inhibitors (TKI), directed at epidermal growth factor receptor (EGFR) is one of the novel effective agents in management of advanced-stage of Non Small Cell Lung cancer (NSCLC). However several candidate predictors have been extensively studied, apart from activating EGFR gene mutations, no reliable biochemical or molecular predictors of response to erlotinib have been validated. The aim of our retrospective study was to evaluate the association of baseline serum albumin with outcomes in a large cohort of patients with advanced-stage NSCLC treated with erlotinib. Clinical data of 457 patients with locally-advanced (III B) or metastatic stage (IV) NSCLC treated with erlotinib were analysed. Serum samples were collected and the measurement was performed one day before the initiation of erlotinib treatment. Before the treatment initiation, low albumin was (<35 g/l) measured in 37 (8.1%) patients and normal albumin (≥ 35 g/l) was measured in 420 (91.9%). The median PFS and OS for patients with low serum albumin was 0.9 and 1.9 months compared to 1.9 and 11.4 months for patients with normal serum albumin (p=0.001 and p<0.001). The multivariate Cox proportional hazards model revealed that EGFR mutation status (HR=2.50; CI: 1.59-3.92; p<0.001) and pretreatment serum albumin (HR=1.73; CI: 1.21-2.47; p=0.003) were significant independent predictive factors for PFS, whereas EGFR mutation status (HR=3.14; CI: 1.70-5.81; p<0.001), stage (HR=1.48; CI: 1.09-2.02; p=0.013), ECOG PS (HR=1.77; CI: 1.37-2.29; p<0.001) and pretreatment serum albumin (HR=4.60; CI: 2.98-7.10; p<0.001) were significant independent predictive factors for OS. In conclusion, the results of present retrospective study indicate that pretreatment hypoalbuminemia is associated with poor outcome of NSCLC patients treated with erlotinib. Based on these results, measuement of serum albumin is an objective laboratory method feasible for estimation of prognosis of patients with advanced-stage NSCLC.

Side Effects and Efficacy of Immunotherapy.

BACKGROUND: Modern immunotherapy based on immune checkpoint inhibitors is an innovative treatment, which is already used in the treatment of a number of malignancies, and many other checkpoint inhibitors have been investigated in clinical trials. Monoclonal antibodies against CTLA-4 (cytotoxic T-lymphocyte antigen-4) and PD-1 (programmed cell death-1) or PD-L1 (programmed cell death-1 ligand) are the most commonly used agents. The side effects of these treatments are similar in nature to those of autoimmune diseases. Recently, increasing evidence has indicated that some adverse effects of immunotherapy are associated with the beneficial effect of this treatment. PURPOSE: The aim of this review was to summarize current knowledge of the association between the adverse effects of checkpoint inhibitors and the outcomes of patients treated with this therapy. CONCLUSION: The association between the effect of immunotherapy and the occurrence of adverse reactions has been identified in a number of studies. It has been best documented in patients with malignant melanoma, non-small cell lung cancer, and renal cell carcinoma. Many studies published so far are limited by the relatively low number of patients and their retrospective design, leaving many questions still unanswered. This work was supported by the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic and by the Charles University Research Fund (Progres Q39) and by the European Regional Development Fund-Project „Application of Modern Technologies in Medicine and Industry” (No. CZ.02.1.01/0.0/0.0/17_048/0007280). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 3. 11. 2019 Accepted: 8. 12. 2019.