Overall survival of stage IV non-small cell lung cancer patients treated with Viscum album L. in addition to chemotherapy, a real-world observational multicenter analysis

Abstract

BackgroundStage IV non-small cell lung cancer (NSCLC) is associated with a five-year survival rate of around 1%. Treatment with Viscum album L. (VA) extracts has been shown to reduce chemotherapy (CTx)-related adverse events, decrease CTx dose reductions and improve quality of life in a number of cancers. Recent data suggest a beneficial effect of add-on treatment with Viscum album L. (VA, European mistletoe) on survival in cancer patients. The objective of this study was to evaluate the effect of VA in addition to chemotherapy on survival in stage IV NSCLC patients.MethodsThe observational study was conducted using data from the Network Oncology clinical registry which is an accredited conjoint clinical registry of German oncological hospitals, practitioners and out-patient centers.Patients were included if they had stage IV NSCLC at diagnosis, lived at least for four weeks post-diagnosis and received chemotherapeutic treatment. Patients with EGFR mutations as well as patients receiving tyrosine kinase inhibitors or immune checkpoint inhibitors were not included. Overall survival and impact on hazard in patients with chemotherapy (CTx) to patients receiving CTx plus VA were compared. To identify factors associated with survival and to address potential sources of bias a multivariate analyses using Cox proportional hazard model was performed.ResultsThe median age of the population was 64.1 years with 55.7% male patients. The highest proportion of patients had adenocarcinoma (72.2%) and most of the patients were current or past smokers (70.9%). Of 158 stage IV NSCLC patients, 108 received CTx only and 50 additional VA. Median survival was 17.0 months in the CTx plus VA group (95%CI: 11.0–40.0) and was 8.0 months (95%CI: 7.0–11.0) in the CTx only group (χ2 = 7.2, p = .007). Overall survival was significantly prolonged in the VA group (HR 0.44, 95%CI: 0.26–0.74, p = .002). One-year and three-year overall survival rates were greater with CTx plus VA compared to CTX alone (1y: 60.2% vs. 35.5%; 3y: 25.7% vs. 14.2%).ConclusionOur findings suggest that concomitant VA is positively associated with survival in stage IV NSCLC patients treated with standard CTx. These findings complement pre-existing knowldedge of add-on VA’s clinical impact, however, results should be interpreted with caution in light of the study’s observational character.

Overall Survival of Nonmetastasized NSCLC Patients Treated With Add-OnViscum albumL: A Multicenter Real-World Study

“…This may be due to the fact that stage IV rather than stages I to IIIA NSCLC patients comply with long-term (>4 weeks) VA treatments: in a recently published real-world study, 31.6% of stage IV NSCLC patients applied long-term add-on VA therapy. 24 The latter number is in line with a study revealing that between 23% and 66% of lung cancer patients seek and continuously apply integrative oncology treatment options. 39 Even up to 77% of lung cancer patients are applying add-on complementary therapies including VA therapy, but the respective study indicated that these patients are mainly late-stage (IIIB and IV) lung cancer patients.…”

Cost-effectiveness of real-world administration of chemotherapy and add-on Viscum album L. therapy compared to chemotherapy in the treatment of stage IV NSCLC patients

“…In a recent published real-world data study on patients with stage IV NSCLC we already demonstrated that patients receiving combinatorial CTx plus add-on VA had a longer mean OS and that this combinatorial treatment was significantly associated with a reduced risk of death compared to patient’s only receiving CTx [ 21 ]. These results are consistent with other published data on the clinical effects of combinatorial VA therapy in cancer patients [ 22 – 25 ].…”

“…For the calculation of survival outcome and hazard risks, Kaplan Meier survival analyses, right-censored time-to-event analyses and, to reduce potential bias, multivariate stratified Cox proportional hazard analyses were performed as previously reported [21], utilizing the R-packages 'survival' (version 3.1-8), 'prodlim' (version 2019.11.13), ggplot2 (version 3.2.1) and 'survminer' (version 0.4.6). Prior Cox proportional hazard analysis, verification analyses were performed whether or not proportional hazard assumptions were met.…”

Cost-Effectiveness of Real-World Administration of Concomitant Viscum album L. Therapy for the Treatment of Stage IV Pancreatic Cancer

“…For the survival outcome, Kaplan-Meier survival and multivariate stratified Cox proportional hazard analyses were calculated as previously reported [25]. e start date for survival analysis was the date of first diagnosis of stage IV pancreatic cancer.…”