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    Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: A real-life data of the Turkish Oncology Group
    (Springer, 2022) Gürbüz, Mustafa; Kutlu, Yasin; Akkuş, Erman; Köksoy, Elif Berna; Köse, Naziyet; Öven, Bala Başak; Uluç, Başak Oyan; Demiray, Atike Gökçen; Erdem, Dilek; Demir, Bilgin; Turhal, Nazım Serdar; Uskent, Necdet; Akbaş, Sinem; Selçukbiricik, Fatih; İnal, Ali; Bilici, Ahmet; Kılıçkap, Saadettin
    Purpose Atezolizumab has been shown to be efective and safe in randomized trial in the frst-line treatment of extensivestage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efcacy and safety of atezolizumab combined with chemotherapy in the frst-line treatment of extensive-stage SCLC. Methods This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a frst-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis. Results A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1–8) and atezolizumab cycle was 7 (1–32). After median 11.9 months of follow-up, median PFS and OS was 6.8 months (95%CI 5.7–7.8), and 11.9 months (95%CI 11–12.7), respectively. The ORR was 61.9%. ECOG-PS (p=0.002) and number of metastatic sites (p=0.001) were associated with PFS and pack-year of smoking (p=0.05), while ECOG-PS (p=0.03) and number of metastatic sites (p=0.001) were associated with OS. Hematological side efects were common and toxicities were manageable. Conclusion This real-life data confrm the efcacy and safety of atezolizumab in combination with chemotherapy in frstline treatment of extensive-stage SCLC.
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    Real-life comparison of afatinib and erlotinib in non-small cell lung cancer with rare EGFR exon 18 and exon 20 mutations: a Turkish Oncology Group (TOG) study
    (Springer, 2022) Tatlı , Ali Murat; Erdem, Dilek; Göker, Erdem; Çelik, Emir; Demirci, Nebi Serkan; Sakin, Abdullah; Atçı , Muhammed Mustafa; Bayram, Ertuğrul; Akın Telli, Tuğba; Bilgin, Burak; Bilici, Ahmet; Akangündüz , Baran; Ballı, Sevinç; Demirkazık, Ahmet; Selçukbiricik, Fatih; Menekşe, Serkan; Çavdar, Eyyüp; Öztürk, Akın; Türkmen Bekmez, Esma; Turhal, Serdal; Kılıçkap, Sadettin; Yıldırım, Hasan Çağrı; Oyan, Başak; Aksoy, Asude; Paksoy Türköz, Fatma; Kut, Engin; Katgı, Nuran; Sakalar, Teoman; Akyol, Murat; Ellez, Halil İbrahim; Topçu, Atakan; Erdoğan, Atike Pınar; Pılancı, Kezban Nur; Hedem, Engin; Arak, Hacı; Akdeniz, Nadiye; Alan, Özkan; Yapar, Burcu; Nart, Deniz; Yumuk, Perran Fulden
    Objectives To compare the survival of frst- and second-generation tyrosine kinase inhibitors (TKIs) in patients with rare EGFR exon 18 and exon 20 mutation-positive non-small cell lung cancer (NSCLC). Materials and methods We retrospectively evaluated survival characteristics of 125 patients with EGFR exon 18 and exon 20 mutated NSCLC who received erlotinib or afatinib as frst line treatment between 2012 and 2021 from 34 oncology centres. Since exon 20 insertion is associated with TKI resistance, these 18 patients were excluded from the study. Results EGFR exon 18 mutations were seen in 60%, exon 20 mutations in 16%, and complex mutations in 24% of the patients with NSCLC who were evaluated for the study. There were 75 patients in erlotinib treated arm and 50 patients in afatinib arm. Patients treated with erlotinib had progression-free survival time (PFS) of 8.0 months and PFS was 7.0 months in the afatinib arm (p=0.869), while overall survival time (OS) was 20.0 vs 24.8 months, respectively (p=0.190). PFS of exon 18 mutated arm was 7.0 months, exon 20 mutated arm was 4.3 months, and complex mutation positive group was 17.3 months, and this was statistically signifcant (p=0.036). The longest OS was 32.5 months, seen in the complex mutations group, which was not statistically diferent than exon 18 and in exon 20 mutated groups (21.0 and 21.2 months, respectively) (p=0.323). Conclusion In this patient group, especially patients with complex mutations are as sensitive to EGFR TKI treatment similar to classical mutations, and in patients with rare exon 18 and exon 20 EGFR mutation both frst- and second-generation EGFR-TKIs should be considered, especially as frst- and second-line options.
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    Response to first?line chemotherapy regimen is associated with efficacy of ımmune checkpoint blockade therapies in patients with metastatic urothelial carcinoma
    (Springer Link, 2021) Tural, Deniz; Selçukbiricik, Fatih; Ölmez, Ömer Fatih; Sümbül, Ahmet Taner; Erman, Mustafa; Kılıçkap, Saadettin
    Background: Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. Patients and methods: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher's exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. Results: The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio [HR] = 1.9; p = 0.04}, ECOG PS ? 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis. Conclusions: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.