Browsing by Author "Kilickap, Saadettin"

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Association of Age with Breast Cancer Clinical and Pathological Factors: Analysis of Turkish National Breast Cancer Registry
(2015) Benekli, Mustafa; Altundag, Kadri; Dumanli, Esra; Isikdogan, Abdurrahman; Karaoglu, Aziz; Tekin, Salim Basol; Oksuzoglu, Berna; Kocer, Murat; Sevinc, Alper; Boruban, Melih Cem; Turna, Hande; Uslu, Ruchan; Ozyilkan, Ozgur; Yalcin, Bulent; Coskun, Ugur; Kilickap, Saadettin; Dogu, Gamze Gokoz; Ozturk, Banu; Gumus, Mahmut; Buyukberber, Suleyman; Uncu, Dogan; Kara, Oguz; Aliustaoglu, Mehmet; Ozkan, Metin; Cicin, Irfan; Elkiran, E. Tamer; Dane, Faysal; Avci, Nilufer; Ulas, Arife; Ozdemir, Feyyaz; Kaya, Ali Osman
Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial
(2021) Sezer, Ahmet; Kilickap, Saadettin; Gumus, Mahmut; Bondarenko, Igor; Ozguroglu, Mustafa; Gogishvili, Miranda; Turk, Haci M.; Cicin, Irfan; Bentsion, Dmitry; Gladkov, Oleg; Clingan, Philip; Sriuranpong, Virote; Rizvi, Naiyer; Gao, Bo; Li, Siyu; Lee, Sue; McGuire, Kristina; Chen, Chieh I; Makharadze, Tamta; Paydas, Semra; Nechaeva, Marina; Seebach, Frank; Weinreich, David M.; Yancopoulos, George D.; Gullo, Giuseppe; Lowy, Israel; Rietschel, Petra; 33581821
Background We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%. Methods In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged >= 18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted of patients with PD-L1 of at least 50% per 22C3 assay done according to instructions for use. Adverse events were assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT03088540 and is ongoing. Findings Between June 27, 2017 and Feb 27, 2020, 710 patients were randomly assigned (intention-to-treat population). In the PD-L1 of at least 50% population, which consisted of 563 patients, median overall survival was not reached (95% CI 17.9-not evaluable) with cemiplimab (n=283) versus 14.2 months (11.2-17.5) with chemotherapy (n=280; hazard ratio [HR] 0.57 [0.42-0.77]; p=0.0002). Median progression-free survival was 8.2 months (6.1-8.8) with cemiplimab versus 5.7 months (4.5-6.2) with chemotherapy (HR 0.54 [0.43-0.68]; p<0.0001). Significant improvements in overall survival and progression-free survival were also observed with cemiplimab in the intention-to-treat population despite a high crossover rate (74%). Grade 3-4 treatment-emergent adverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy. Interpretation Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
Characteristics of Turkish Colorectal Cancer Patients and Bevacizumab Preference.
(2017) Cicin, Irfan; Gumus, Mahmut; Uncu, Dogan; Ozkan, Metin; Kilickap, Saadettin; Elkiran, Tamer E.; Isikdogan, Abdurrahman; Karaoglu, Aziz; Oksuzoglu, Berna; Ozdemir, Feyyaz; Turna, Hande; Kara, Oguz; Ozyilkan, Ozgur; Guducu, Merve; Erdogan, Alper; Uslu, Ruchan
Crizotinib Efficacy and Safety in Patients with Advanced NSCLC Harboring MET Alterations: A Real-Life Data of Turkish Oncology Group
(2022) Gurbuz, Mustafa; Kilickap, Saadettin; Bilici, Ahmet; Karadurmus, Nuri; Sezer, Ahmet; Sendur, Mehmet Ali Nahit; Paydas, Semra; Artac, Mehmet; Fulden Yumuk, Perran; Gursoy, Pinar; Uysal, Mukremin; Senol Coskun, Hasan; Tatli, Ali Murat; Selcukbiricik, Fatih; Disel, Umut; Koksoy, Elif Berna; Guven, Deniz Can; Ugrakli, Muzaffer; Akkus, Erman; Yucel, Sebnem; Erol, Cihan; Karakaya, Serdar; Sakalar, Teoman; Khanmammadov, Nijat; Paksoy, Nail; Demirkazik, Ahmet; 36550824
Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.
Cutaneous Melanoma in Turkey: Analysis of 1157 Patients in the Melanoma Turkish Study
(2015) Abali, Huseyin; Celik, Ismail; Karaca, Burcak; Turna, Hande; Saglam, Esra Kaytan; Akman, Tulay; Oztop, Ilhan; Coskun, Hasan Senol; Turhal, Nazim Serdar; Sezer, Ahmet; Nayir, Erdinc; Demir, Gokhan; Budakoglu, Burcin; Issikdogan, Abdurrahman; Engin, Huseyin; Kilickap, Saadettin; Coskun, Ugur; Oyan, Basak; Harputluoglu, Hakan; Er, Ozlem; Kavgaci, Halil; Elkiran, Tamer; 26416068
Purpose: To develop a large Turkish National Melanoma registry in order to define demographic and clinicopathologic characteristics of patients with melanoma. Methods: The data was collected from 1635 patients with melanoma through a web-based registry system in 22 centers. Herein we present the results of 1157 patients with cutaneous melanoma. Results: The patient median age was 56.4 years and 646 (55.8%) were males. The commonest subtype was superficial spreading type (357, 30.9%). The commonest primary site was the lower extremities (N=353, 30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only 104 (12.5%) patients had a thickness <1mm. Among 694 patients with available data, 136 (19.6%) presented with stage 4 disease while the most frequent stage was stage 3, encountered in 393 (56.6% patients). Conclusion: Our melanoma registry is the largest in our country providing a snapshot view of cutaneous melanoma and its care. Our patients presented with more advanced stages and they had worse prognosis compared to SEER database.
First-Line Cemiplimab Monotherapy and Continued Cemiplimab Beyond Progression Plus Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 50% Or More (EMPOWER-Lung 1): 35-Month Follow-Up From A Multicentre, Open-Label, Randomised, Phase 3 Trial
(2023) Ozguroglu, Mustafa; Kilickap, Saadettin; Sezer, Ahmet; Gumus, Mahmut; Bondarenko, Igor; Gogishvili, Miranda; Nechaeva, Marina; Schenker, Michael; Cicin, Irfan; Ho, Gwo Fuang; Kulyaba, Yaroslav; Zyuhal, Kasimova; Scheusan, Roxana-Ioana; Garassino, Marina Chiara; He, Xuanyao; Kaul, Manika; Okoye, Emmanuel; Li, Yuntong; Li, Siyu; Pouliot, Jean-Francois; Seebach, Frank; Lowy, Israel; Gullo, Giuseppe; Rietschel, Petra; 37591293
Background: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.Methods: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged >= 18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.Findings: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 261 months (95% CI 221-318; 149 [52%] of 284 died) versus 133 months (105-162; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 057, 95% CI 046-071; p<00001), median progression-free survival was 81 months (95% CI 62-88; 214 events occurred) in the cemiplimab group versus 53 months (43-61; 236 events occurred) in the chemotherapy group (HR 051, 95% CI 042-062; p<00001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 66 months (61-93) and overall survival of 151 months (113-187). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signalsINTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.Copyright (c) 2023 Elsevier Ltd. All rights reserved.
Generic Imatinib Mesylate is as Effective as Original Glivec in the Clinical Management of CML
(2015) Malkan, Umit Y.; Aksu, Salih; Aktimur, Sude H.; Atay, Hilmi; Bektas, Ozlen; Buyukasik, Yahya; Demiroglu, Haluk; Eliacik, Eylem; Esme, Mert; Hacihanefioglu, Abdullah; Gunes, Gursel; Goker, Hakan; Karakus, Sema; Kilickap, Saadettin; Koca, Ebru; Ozcebe, Osman I.; Sayinalp, Nilgun; Tarkun, Pinar; Turgut, Mehmet; Haznedaroglu, Ibrahim C.
Unsustainable drug prices in chronic myeloid leukemia (CML) and cancer may be causing harm to patients. The aim of this multi-center study is to assess the efficacy of generic imatinib mesylate (IM) over Glivec in terms of hematological, cytogenetic, and molecular responses in CML. The data of 120 CML patients, who were treated with generic or original form of IM, were obtained from six different hematology clinics in Turkey between the years of 2009-2014 and analyzed retrospectively. Initial evaluation revealed that only one patient who was using original molecule switched to second generation tyrosine kinase inhibitor (TKI). In this period, hematological response(HR) was observed in 99.2% of the patients, cytogenetic response (CR) was observed in 88.7% of the patients (47 of 53), and molecular response (MR) was observed in 75% of the patients. Clinicians had a tendency to prefer generic molecules in each sequent visit, and this switch rate was statistically significant (p<0.001). 11 patients, who were using original molecules during all cohorts, switched to second generation TKI. On the other hand, only one patient, who was using generic molecules, switched to second generation TKI. Our paper may help to clarify the doubts about the efficacy of generic IM compared to original molecule. In our study we did not find any significant difference in HR, CR, and MR for original and generic drugs in each visit. Herein, we find low rates of need to switch to second generation TKIs with generic IM and no difference in treatment responses between generic and original molecules that confirms the non-inferiority of generic TKIs over original molecules.
Geographic Variations of Clinical Characteristics in Breast Cancer: Analysis of Turkish National Breast Cancer Registry
(2015) Kilickap, Saadettin; Altundag, Kadri; Dumanli, Esra; Gumus, Mahmut; Uslu, Ruchan; Ozyilkan, Ozgur; Yalcin, Bulent; Kara, Oguz; Dogu, Gamze Gokoz; Ozturk, Banu; Kaya, Ali Osman; Aliustaoglu, Mehmet; Uncu, Dogan; Ozdemir, Feyyaz; Cicin, Irfan; Ozkan, Metin; Kocer, Murat; Turna, Hande; Buyukberber, Suleyman; Benekli, Mustafa; Coskun, Ugur; Karaoglu, Aziz; Tekin, Salim Basol; Dane, Faysal; Avci, Nilufer; Ulas, Arife; Oksuzoglu, Berna; Sevinc, Alper; Boruban, Melih Cem
Lung Cancer in Turkey
(2022) Cangir, Ayten Kayi; Yumuk, Perran Fulden; Sak, Serpil Dizbay; Akyurek, Serap; Eralp, Yesim; Yilmaz, Ulku; Selek, Ugur; Eroglu, Atilla; Tatli, Ali Murat; Dincbas, Fazilet Oner; Kilickap, Saadettin; Sendur, Mehmet Ali Nahit; Dilektasli, Asli Gorek; Bozcuk, Hakan Sat; Ozkok, Serdar; Oztop, Ilhan; Topkan, Erkan; Dilege, Sukru; Kaya, Akin; Demirkazik, Ahmet; 36192076
Patient-Reported Outcomes with Cemiplimab Monotherapy for First-Line Treatment of Advanced Non-Small Cell Lung Cancer with PD-L1 Of >= 50%: The EMPOWER-Lung 1 Study
(2023) Gumus, Mahmut; Chen, Chieh-, I; Ivanescu, Cristina; Kilickap, Saadettin; Bondarenko, Igor; Ozguroglu, Mustafa; Gogishvili, Miranda; Turk, Haci M.; Cicin, Irfan; Harnett, James; Mastey, Vera; Naumann, Ulrike; Reaney, Matthew; Konidaris, Gerasimos; Sasane, Medha; Brady, Keri J. S.; Li, Siyu; Gullo, Giuseppe; Rietschel, Petra; Sezer, Ahmet; 36308296
Background In the EMPOWER-Lung 1 trial (, NCT03088540), cemiplimab conferred longer survival than platinum-doublet chemotherapy for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) >= 50%. Patient-reported outcomes were evaluated among trial participants. Methods Adults with NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. At baseline and day 1 of each treatment cycle, patients were administered the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Lung Cancer Module (QLQ-LC13) questionnaires. Mixed-model repeated measures analysis estimated overall change from baseline for PD-L1 >= 50% and intention-to-treat populations. Kaplan-Meier analysis estimated time to definitive deterioration. Results In PD-L1 >= 50% patients (cemiplimab, n = 283; chemotherapy, n = 280), baseline QLQ-C30 and QLQ-LC13 scores showed moderate-to-high functioning and low symptom burden. Change from baseline favored cemiplimab on global health status/quality of life (GHS/QOL), functioning, and most symptom scales. Risk of definitive deterioration across functioning scales was reduced versus chemotherapy; hazard ratios were 0.48 (95% CI, 0.32-0.71) to 0.63 (95% CI, 0.41-0.96). Cemiplimab showed lower risk of definitive deterioration for disease-related (dyspnea, cough, pain in chest, pain in other body parts, fatigue) and treatment-related symptoms (peripheral neuropathy, alopecia, nausea/vomiting, appetite loss, constipation, diarrhea) (nominal p < .05). Results were similar in the intention-to-treat population. Conclusions Results support cemiplimab for first-line therapy of advanced NSCLC from the patient's perspective. Improved survival is accompanied by improvements versus platinum-doublet chemotherapy in GHS/QOL and functioning and reduction in symptom burden.
Prognostic factors for survival in patients with metastatic malign melanoma treated with ipilimumab: Turkish Oncology Group study
(2019) Urun, Yuksel; Yasar, H. Arzu; Turna, Hande; Esin, Ece; Sedef, A. Murat; Alkan, Ali; Oksuzoglu, Berna; Ozdemir, Nuriye; Sendur, M. A. Nahit; Sezer, Ahmet; Kilickap, Saadettin; Utkan, Gungor; Akman, Tulay; Akbulut, Hakan; Celik, Ismail; Abali, Huseyin; 30400750
Purpose Studies in the last decade show survival improvement with checkpoint blocker therapy in patients with metastatic malign melanoma. Our purpose was to define the efficacy of ipilimumab according to the patient's baseline characteristics including absolute lymphocytes count. Methods We collected the data of 97 patients with advanced malign melanoma treated with ipilimumab (3 mg/kg, q3w) retrospectively. Log-rank test was used to analyze the univariate effects of patient's characteristics (age, gender, metastatic sites, ECOG PS, type of melanoma, lactic dehydrogenase levels, anemia, lymphocytes (L), neutrophils (N), N/L ratio), c-kit and BRAF status. Survival analyses were estimated with Kaplan-Meier method. Cox regression analysis was used to assess the possible factors identified with log-rank test. Results The median age was 58, and 58% were male and 90% of patients had at least one prior systemic therapy. The median survival was 9.7 months for all patients; and the 12- and 24-month survival rates were 43% and 19%, respectively. Absolute lymphocytes count, lactic dehydrogenase level, bone metastasis, the number of metastatic sites, and RECIST response were significantly related to survival. After Cox regression analysis, RECIST response (complete or partial response), absolute lymphocytes count (more than 1500/mm(3)) and the number of metastatic sites (less than three sites) remained as significant independent prognostic factors for longer survival. Conclusion Ipilimumab improved survival of patients with metastatic malign melanoma. However, patients with fewer metastatic sites and higher absolute lymphocytes count have a significantly better benefit. To determine if these markers could be used to direct patient therapy, further validation analysis is needed.
Prognostic factors for survival in patients with mucosal and ocular melanoma treated with ipilimumab: Turkish Oncology Group study
(2020) Yasar, H. Arzu; Turna, Hande; Esin, Ece; Sedef, A. Murat; Alkan, Ali; Oksuzoglu, Berna; Ozdemir, Nuriye; Sendur, M. A. Nahit; Sezer, Ahmet; Kilickap, Saadettin; Utkan, Gungor; Akbulut, Hakan; Celik, Ismail; Abali, Huseyin; Urun, Yuksel; 0000-0002-6445-1439; 30924738; AAD-2667-2020
Objective To evaluate prognostic factors associated with the use of ipilimumab in patients with mucosal and uveal melanoma. Methods In this multicenter, retrospective study, 31 patients with uveal and mucosal melanoma diagnosed between 2010 and 2017 were enrolled. Patients' characteristics, metastatic disease sites, treatment before ipilimumab therapy, performance status, hemoglobin, lactate dehydrogenase levels, B-RAF and c-kit mutation status, toxicity, and survival data were assessed for patients with mucosal and uveal melanoma. SPSS version 17 was used for statistical analysis. Kaplan-Meier method was used for survival analysis. The log-rank test was used for univariate analyses. The Cox regression analysis was used to test the association between multivariate variables and survival. The p-value of less than 0.05 was considered statistically significant. Results Twenty patients had uveal and eleven patients had mucosal melanoma. The median overall survival was seven months (95% confidence interval: 1.1-12.7). In univariate analysis, while bone metastasis, anemia, high lactate dehydrogenase level, and more metastatic sites were associated with lower overall survival, better treatment response and administration of ipilimumab in first or second lines were associated with favorable overall survival. In multivariate analysis, only treatment response status and administration of ipilimumab in first or second lines were found to be significant as independent prognostic factors for survival. Conclusion Ipilimumab therapy may be associated with increased survival, but this retrospective small N study makes that hard to definitely conclude.
Re: Combination of radiotherapy and immunotherapy? Do timing and dose matter?
(2019) Urun, Yuksel; Yasar, H. Arzu; Turna, Hande; Kilickap, Saadettin; Sezer, Ahmet; Oksuzoglu, Berna; Ozdemir, Nuriye; Sendur, M. A. Nahit; Abali, Huseyin; 31226917