Real-World Testing Practices, Treatment Patterns and Clinical Outcomes in Patients from Central Eastern Europe with EGFR-Mutated Advanced Non-Small Cell Lung Cancer: A Retrospective Chart Review Study (REFLECT).

The targeted therapy with tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor mutation (EGFRm) in advanced non-small cell lung cancer (NSCLC) changed the treatment paradigm. REFLECT study (NCT04031898) explored EGFR/T790M testing and treatment patterns in EGFRm NSCLC patients receiving first- or second-generation (1G/2G) EGFR TKIs as front-line (1L) in eight countries. Pooled data from Central Eastern Europe (CEE) countries from this study (Bulgaria, Poland, Romania, Slovenia) are presented here. This physician-led chart review study was conducted in patients with confirmed-EGFRm NSCLC initiating 1L 1G/2G EGFR TKIs between 2015-2018. The CEE cohort included 389 patients receiving 1L erlotinib (37%), afatinib (34%), and gefitinib (29%). Overall, 320 (82%) patients discontinued 1L, and 298 (77%) progression events were registered. Median progression free survival on 1L TKIs was 14.0 (95% CI: 12.6-15.6) months. Median overall survival from 1L start was 26.6 (95% CI: 24.1-29.0) months. Attrition rate between 1L and next line was 30%. Among patients with 1L progression, 200 (67%) were tested for T790M and 58% were positive. This first CEE analysis of treatments and outcomes in EGFRm NSCLC patients highlights the importance of using the most efficacious therapies currently available in 1L to reduce attrition and improve patient outcomes.

Real-world outcomes, treatment patterns and T790M testing rates in non-small cell lung cancer patients treated with first-line first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors from the Slovenian cohort of the REFLECT study.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective treatments for EGFR mutation-positive (EGFRm) non-small cell lung cancer (NSCLC). However, routine clinical practice is different between countries/institutions. PATIENTS AND METHODS: The REFLECT study (NCT04031898) is a retrospective medical chart review that explored real-life treatment and outcomes of EGFRm NSCLC patients receiving first-line (1L) first-/second-generation (1G/2G) EGFR TKIs in 8 countries. This study included adult patients with documented advanced/metastatic EGFRm NSCLC with 1L 1G/2G EGFR TKIs initiated between Jan 2015 - Jun 2018. We reviewed data on clinical characteristics, treatments, EGFR/T790M testing patterns, and survival outcomes. Here, we report data from 120 medical charts in 3 study sites from Slovenia. RESULTS: The Slovenian cohort (median age 70 years, 74% females) received 37% erlotinib, 32% afatinib, 31% gefitinib. At the time of data collection, 94 (78%) discontinuations of 1L TKI, and 89 (74%) progression events on 1L treatment were reported. Among patients progressing on 1L, 73 (82%) were tested for T790M mutation yielding 50 (68%) positive results, and 62 (85%) received 2L treatment. 82% of patients received osimertinib. Attrition rate between 1L and 2L was 10%. The median (95% CI) real-world progression free survival on 1L EGFR TKIs was 15.6 (12.6, 19.2) months; median overall survival (95% CI) was 28.9 (25.0, 34.3) months. CONCLUSIONS: This real-world study provides valuable information about 1G/2G EGFR TKIs treatment outcomes and attrition rates in Slovenian EGFRm NSCLC patients. The reduced attrition rate and improved survival outcomes emphasize the importance of 1L treatment decision.

Incorporation of EGFR mutation status into M descriptor of new TNM classification influences survival curves in non-small cell lung cancer patients.

Background The 8th edition of tumor node metastasis (TNM) staging system for lung cancer introduced a revision of M descriptor. The limitation of new classification to predict prognosis is its focus on anatomical extent of the disease only. Information on molecular status of the tumor significantly influences treatment response and survival; however, data addressing this issue is scarce. This report points to the impact of epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC) patients on survival in view of new M descriptors of TNM classification system. Patients and methods Medical records of 479 consecutive metastatic NSCLC patients treated between 2009 and 2011, all tested for EGFR mutations, were retrospectively reviewed. For 355 patients medical records included sufficient information to be appropriately categorized into one of the new subgroups according to the M descriptor in 8th TNM classification, of those 89 (25.1%) patients harboured EGFR mutations (EGFR-m). Results Median overall survival (mOS) of EGFR-m patients was significantly longer than mOS of patients without EGFR mutations (20.6 months vs. 8.3 months, p < 0.001). Patients with limited disease burden (M1b sub-group) had the longest mOS among EGFR wild type patients (EGFR-wt) and also among EGFR-m patients, 14.4 months and 39.2 month, respectively. In spite of widespread metastatic disease of M1c EGFR-m patients, their mOS (18.8 months) was longer than mOS of oligometastatic EGFR-wt patients (M1b), who had the lowest disease burden (14.4 months). Median follow up was 53.9 months. Conclusions Incorporation of EGFR mutation status in advanced NSCLC further differentiates survival curves of M categories in 8th TNM classification and more precisely predicts survival compared to number of metastasis or number of metastatic sites alone.

Ankle-Brachial Index and Long-Term (10 Years) Survival of Nondiabetic Hemodialysis Patients.

Low (<0.9) and high (>1.4) ankle brachial index (ABI) is associated with a higher cardiovascular (CV) mortality in the general and hemodialysis (HD) population. The aim of our study was to determine the impact of ABI on long-term survival of 52 non-diabetic HD patients. The ABI was determined using an automated, non-invasive waveform analysis device. Patients were divided into three groups: low (<0.9), normal (0.9-1.4) and high (>1.4) ABI. Patients were observed from the date of ABI measurement until their death or ten years. Survival analysis showed higher risk for CV death in HD patients with high ABI compared to normal ABI (log rank test P < 0.027). In Cox regression model adjusted for arterial hypertension, smoking, serum cholesterol and triglycerides, high ABI (P < 0.049) remained a predictor of mortality. The results indicate an association between ABI and long-term survival of non-diabetic HD patients and only high ABI was associated with higher CV mortality.

Ankle-brachial index and cardiovascular mortality in nondiabetic hemodialysis patients.

Atherosclerosis is a leading cause of morbidity and mortality in hemodialysis (HD) patients. Low (<0.90) and high (>1.40) ankle-brachial index (ABI) is known as a non-invasive diagnostic marker for generalized atherosclerosis associated with higher cardiovascular (CV) mortality in the general population. Less is known about associations between ABI and CV mortality in HD patients. The aim of our study was to determine the impact of the ABI on CV mortality in nondiabetic HD patients. Fifty-two nondiabetic HD patients (mean age 59 years, range 22 - 76 years) were enrolled in our study. Twenty-three (44%) were women and 29 (56%) men. The ABI was determined using an automated, non-invasive, waveform analysis device. All patients were divided according to the ABI into three groups: low ABI (<0.9), normal ABI (0.9-1.4) and high ABI (>1.4). The presence of arterial hypertension and smoking was established. Serum cholesterol (HDL and LDL) and triglycerides were measured by routine laboratory methods. Survival rates were analyzed using Kaplan-Meier survival curves. The Cox regression model was used to assess the influence of the ABI on CV outcomes. The model was adjusted for age, arterial hypertension, smoking, cholesterol and triglycerides. Mean ABI value was 1.2 ± 0.3 (range 0.2-2.2). Patients were observed from the date of the ABI measurement until their death or maximally up to 1620 days. Kaplan-Meier survival analysis showed that the risk for CV death was higher for HD patients with low and high ABI compared to normal ABI (log rank test: P < 0.006; P < 0.0001). In the adjusted Cox multivariable regression model low and high ABI (P < 0.011; P < 0.003) remained predictors of mortality in our patients. The results indicate a U-shaped association between the ABI and CV mortality in nondiabetic HD patients and showed that low and high ABI were directly associated with higher mortality of our patients.