Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences

Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. Design, setting, and participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. Outcome measurements and statistical analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. Results and limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47–28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25–5.49) and 9.8 mo (95% CI, 6.7–12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3–4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. Patient summary: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting. Atezolizumab is an effective and tolerable treatment option for patients with urothelial cancer after progression by the chemotherapy. Clinical activity and safety of atezolizumab treatment in real-life patients were consistent with the outcomes of the previous clinical trials in this setting © 202

Baseline clinical characteristics and patient profile of the TURKMI registry: Results of a nation-wide acute myocardial infarction registry in Turkey

PubMed: 32628144Objective: The TURKMI registry is designed to provide insight into the characteristics, management from symptom onset to hospital discharge, and outcome of patients with acute myocardial infarction (MI) in Turkey. We report the baseline and clinical characteristics of the TURKMI population. Methods: The TURKMI study is a nation-wide registry that was conducted in 50 centers capable of percutaneous coronary intervention selected from each EuroStat NUTS region in Turkey according to population sampling weight, prioritized by the number of hospitals in each region. All consecutive patients with acute MI admitted to coronary care units within 48 hours of symptom onset were prospectively enrolled during a predefined 2-week period between November 1, 2018 and November 16, 2018. Results: A total of 1930 consecutive patients (mean age, 62.0±13.2 years; 26.1% female) with a diagnosis of acute MI were prospectively enrolled. More than half of the patients were diagnosed with non-ST elevation MI (61.9%), and 38.1% were diagnosed with ST elevation MI. Coronary angiography was performed in 93.7% and, percutaneous coronary intervention was performed in 73.2% of the study population. Fibrinolytic therapy was administered to 13 patients (0.018%). Aspirin was prescribed in 99.3% of the patients, and 94% were on dual antiplatelet therapy at the time of discharge. Beta blockers were prescribed in 85.0%, anti-lipid drugs in 96.3%, angiotensin converting enzyme inhibitors in 58.4%, and angiotensin receptor blockers in 7.9%. Comparison with European countries revealed that TURKMI patients experienced MI at younger ages compared with patients in France, Switzerland, and the United Kingdom. The most prevalent risk factors in the TURKMI population were hypercholesterolemia (60.2%), hypertension (49.5%), smoking (48.8%), and diabetes (37.9%). Conclusion: The nation-wide TURKMI registry revealed that hypercholesterolemia, hypertension, and smoking were the most prevalent risk factors. TURKMI patients were younger compared with patients in European Countries. The TURKMI registry also confirmed that current treatment guidelines are largely adopted into clinical cardiology practice in Turkey in terms of antiplatelet, anti-ischemic, and anti-lipid therapy. ©Copyright 2020 by Turkish Society of CardiologyAcknowledgments: TURKMI is an investigator-initiated study sponsored by the Turkish Society of Cardiology that receives major funding from Astra-Zeneca Company for this project

Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group

Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities. © 2023 The Author(s)This work was supported by Bristol Myers Squibb, Istanbul, Turkey .Bristol-Myers Squibb, BM

Combination of trastuzumab and taxane-containing intensified chemotherapy in first-line treatment of HER2-positive advanced gastric cancer

Purpose: Taxane-containing combinations are recommended for the first-line therapy of advanced gastric cancer. It is not known which chemotherapy regimen is the best with trastuzumab for HER2-positive patients. The aim of this study was to compare taxane-containing intensified chemotherapy versus standard chemotherapy in combination with trastuzumab in the first-line treatment of HER2-positive advanced gastric adenocarcinoma. Methods: This study is a retrospective multicenter study of the Turkish Oncology Group. A total of 130 HER2-positive patients with inoperable locally advanced, recurrent, or metastatic gastric adenocarcinoma being given chemotherapy plus trastuzumab as the first-line treatment were included from 16 different oncology centers. Trastuzumab combination with intensified chemotherapy including taxane or standard chemotherapy was compared in terms of progression-free survival (PFS), overall survival (OS), and toxicity. Results: There were 108 patients in the standard and 22 patients in the intensified chemotherapy group. PFS of the standard and intensified group were 5.6 months (95% confidence interval [CI] 4.8–6.4) and 5.3 months (95% CI 2.6–8), respectively (p = 0.70). OS of the standard and intensified group were 11.1 months (95% CI 8.3–13.9) and 15.2 months (95% CI 12.7–17.7), respectively (p = 0.03). Repeated analysis excluding patients given any previous therapy revealed similar results. The intensified group had more fever and febrile neutropenia. Conclusion: Trastuzumab combination with intensified chemotherapy provides better OS in first-line treatment of HER2-positive advanced gastric cancer. Further large-scale studies should be performed in HER2-positive patients. © Fondazione IRCCS Istituto Nazionale dei Tumori 2020

Combination of trastuzumab and taxane-containing intensified chemotherapy in first-line treatment of HER2-positive advanced gastric cancer.

PURPOSE: Taxane-containing combinations are recommended for the first-line therapy of advanced gastric cancer. It is not known which chemotherapy regimen is the best with trastuzumab for HER2-positive patients. The aim of this study was to compare taxane-containing intensified chemotherapy versus standard chemotherapy in combination with trastuzumab in the first-line treatment of HER2-positive advanced gastric adenocarcinoma. METHODS: This study is a retrospective multicenter study of the Turkish Oncology Group. A total of 130 HER2-positive patients with inoperable locally advanced, recurrent, or metastatic gastric adenocarcinoma being given chemotherapy plus trastuzumab as the first-line treatment were included from 16 different oncology centers. Trastuzumab combination with intensified chemotherapy including taxane or standard chemotherapy was compared in terms of progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: There were 108 patients in the standard and 22 patients in the intensified chemotherapy group. PFS of the standard and intensified group were 5.6 months (95% confidence interval [CI] 4.8-6.4) and 5.3 months (95% CI 2.6-8), respectively (p = 0.70). OS of the standard and intensified group were 11.1 months (95% CI 8.3-13.9) and 15.2 months (95% CI 12.7-17.7), respectively (p = 0.03). Repeated analysis excluding patients given any previous therapy revealed similar results. The intensified group had more fever and febrile neutropenia. CONCLUSION: Trastuzumab combination with intensified chemotherapy provides better OS in first-line treatment of HER2-positive advanced gastric cancer. Further large-scale studies should be performed in HER2-positive patients

LID - 10.1016/j.euf.2020.09.010 [doi]

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. OBJECTIVE: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. RESULTS AND LIMITATIONS: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. CONCLUSIONS: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. PATIENT SUMMARY: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting