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130 Background: Tyrosine kinase inhibitors (TKI) are the most common oral drugs in cancer patients. Similarly, proton pump inhibitors (PPI) are commonly used to relieve dyspeptic symptoms in patients with cancer. However, gastric pH levels may affect the absorption of TKI through the gastrointestinal system. However, all TKIs do not have the same chemical structure, and the absorption rate of each TKI depends on their solubility in different gastric pH levels. Limited data is available about the clinical outcomes of concomitant use of PPI and regorafenib in patients with metastatic colorectal cancer (mCRC). We present here the results of the multicenter study following the initial results of our single-center experience. Methods: Patients with mCRC treated with regorafenib were included in this multicenter and retrospective study. Patients prescribed PPI after initiation of regorafenib were assigned to the PPI user group, and the remaining patients were assigned to the PPI non-user group. To exclude immortal time bias, the log-rank test was performed between PPI non-user and all patients. The primary outcome was overall survival (OS), and secondary outcomes were time to treatment failure (TTF) and adverse events (AEs) profile. Results: Two hundred and seventy-two patients from eight cancer centers were included in this study. Most patients were male (59.9%), had liver metastasis (62.1%), and received regorafenib in the third line (52.2%). The median age at the initiation of regorafenib was 60 years (interquartile range (IQR): 51-66)). Eastern Cooperative Oncology Group performance score was 0 or 1 in approximately three out of four patients. The rate of patients with K-RAS mutation was 46.7%. There were 131 (48.2%) and 141 (51.8%) in the PPI user and non-user groups, respectively. The most prescribed PPI was pantoprazole (40.4%). At a median 34.2 months follow-up, the median OS was 6.9 months (95% Confidence Interval (CI): 5.3-8.5) and 7.7 months (95% CI:6.6-8.8) in the PPI non-user and all patients, respectively. No statistical significance was observed between the groups (p = 0.913). The median TTF was 3.3 months (95% CI: 2.6-3.9) and 3.4 months (95% CI:2.9-4.0) in the PPI non-user and all patients, respectively. No statistical significance was observed between the groups (p = 0.651). In the time-dependent covariate Cox regression model, there was no difference between PPI user and non-user groups in OS and TTF (adjusted Hazard Ratio (aHR):0.96, 95% CI:0.74-1.24, p = 0.735 for OS; aHR:0.88, 0.68-1.14, p = 0.354 for TTF). The rates of all AEs were also similar in the PPI user and non-user groups (p = 0.628). Conclusions: To our knowledge, this was the first study evaluating the effect of concomitant use of PPI and regorafenib in patients with mCRC, and no adverse survival and safety outcome was observed with the concomitant use of PPI and regorafenib in those patients.

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4\%), DCF (17.4\%) and ECF (8.1\%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2\%, R0 resection rate 86.4\%, and D2 dissection rate was 66.8\%. Rate of pCR and near-CR (24\%), and R0 resection (84\%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95\% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95\% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68\%). We still do not know which NACT regimen is the best choice for daily practice. Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.

Aim: Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS). Patients and methods: This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort. Results: Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively. Conclusion: Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations.

Thiols are the organic compounds of the antioxidant system. There is limited data in the literature concerning chemotherapy (CT) in cancer and thiol balance. In this study, we aimed to evaluate the possible changes of thiol/disulfide levels with the recurrent CT cycles and type of cancer.The 40 healthy individuals and 40 patients who had been newly diagnosed with early-stage breast, ovary and endometrium cancer receiving adjuvant CT. Blood samples were taken from all patients three times as basal and after the first and second CT sessions.We compared preadjuvant treatment levels of thiol and disulfide parameters in the patients group with the control group. The median of native thiol and total thiol was found to be higher in the control group than in the study group (P0.001). In addition, disulfide/native thiol and disulfide/total thiol rates were found to be higher in the patient group (P = 0.001). When we look at the comparison before and after CT in the patient group, disulfide/native thiol and disulfide/total thiol rates, which represent increased oxidative stress (OS) levels were found to be higher after CT than before CT measurement (P0.016).This is the first study, which has researched the relationship between cancer type and thiol compounds and changes of thiol compounds during CT therapy, by using the method designed by Erel and Neşelioğlu. In this study, we found that pre-CT thiol disulfide balance in cancer patients shifted toward disulfide direction and OS levels may increase after repetitive CT sessions.

The new second-generation tyrosine kinase inhibitors (TKIs) have superior survival outcome and worse toxicity profile when compared with first-generation TKIs according to the results of clinical trials. However, there are limited studies that investigate the efficacy and safety of the new generation TKIs in real-world patients. Thus, we aimed to compare the efficacy and safety of the afatinib, an irreversible inhibitor of ErbB family receptor, and first-generation TKIs in real-world patients. We included advanced nonsmall cell lung cancer (NSCLC) patients who had EGFR exon 19del mutation and treated with afatinib or first-generation TKIs as upfront treatment between 2016 and 2020. All patient's information was collected retrospectively. The study cohort was divided as afatinib arm and erlotinib/gefitinib arm. A total of 283 patients at the 24 oncology centers were included. The 89 and 193 of whom were treated with afatinib and erlotinib/gefitinib, respectively. After 12.9 months (mo) of follow-up, the median PFS was statistically longer in the afatinib arm than erlotinib/gefitinib arm (19.3 mo vs. 11.9 mo, p: 0.046) and the survival advantage was more profound in younger patients (

Background Pan-immune-inflammation value (PIV) is an easily accessible immune marker based on peripheral blood to estimate prognosis in patients with cancer. This study evaluates the prognostic value of PIV in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab. Methods In this retrospective cohort study, patients with mRCC treated with nivolumab in the second line and beyond were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. PIV was calculated by using the following formula: neutrophil (103/mm3) x monocyte (103/mm3) x platelet (103/mm3) / lymphocyte (103/mm3). Results A total of 152 patients with mRCC were included in this study. According to cut-off value for PIV, 77 (50.7%) and 75 (49.3%) patients fell into PIV-low (\(\le\)372) and PIV-high (>372) groups, respectively. In multivariate analysis, PIV-high (HR:1.64, 95% CI: 1.04–2.58, p = 0.033 for overall survival (OS); HR:1.55, 95% CI: 1.02–2.38, p = 0.042 for progression-free survival (PFS)) was independent risk factor for OS and PFS after adjusting for confounding variables such as performance score, the International mRCC Database Consortium (IMDC) risk score, and liver metastasis. Conclusion This study established that pre-treatment PIV might be a prognostic biomarker in patients with mRCC treated with nivolumab in the second line and beyond.

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.

PurposeNeoadjuvant chemotherapy(NACT) in gastroesophageal junction(GEJ) and gastric cancer(GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT in order to compare the efficacy and toxicity profile of different chemotherapy regimens in our country.Methods This retrospective multicenter study included locally advanced GC and GEJ cancer patients who received NACT, and had pathological response evaluation between 2007 and 2021. Relation between CT regimens and pathological evaluation were analyzed. Results A total of 728 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-68). Most frequent NACT regimens used were FLOT (65%), DCF (18%) and ECF (8.1%), respectively. In the total study group pCR rate was 8.2%, R0 resection rate 88.5%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (26.4%), and R0 resection (92.6%) were higher in FLOT arm (p= 0.005 and ConclusionIn our real-life study, FLOT regimen has superior survival outcome despite worse toxicity profile. Clinicians should tailor treatment regimens according to patients’ multifactorial status and comorbidities for to obtain best outcomes.

Purpose: In the ToGA trial for HER2-positive advanced gastric cancer, cisplatin plus fluoropyrimidine was given for 6 cycles; trastuzumab was given until disease progression. However, there is a lack of real-life data about trastuzumab maintenance after 6 cycle chemotherapy. This study aims to present real-life data of trastuzumab ± capecitabine maintenance after 6 cycles of platinum, fluoropyrimidine, and trastuzumab in non-progressive patients. Methods: This is a retrospective multicenter study of the Turkish Oncology Group. A total of 35 HER2-positive, inoperable locally advanced, recurrent, or metastatic gastric adenocarcinoma patients being non-progressive at the end of 6 cycle chemotherapy and being given trastuzumab ± capecitabine as maintenance treatment were included from sixteen oncology centers. Baseline characteristics, objective tumor responses, progression free and overall survival data, and toxicities were determined. Results: About 68% of the patients were given CF, and 32% were given FOLFOX with trastuzumab as the first-line treatment. The best response in 6 cycle chemotherapy was complete 8 (22%), partial 24 (68%), and stable disease 3 (8%). All patients had trastuzumab maintenance (median cycle 13; range 7–51), and 49% of the patients had capecitabine with trastuzumab (median capecitabine cycle 6; range 2–30). The median PFS of the patients was 12.0 months (95% CI 10.3–13.7), and median OS was 17.4 months (95% CI 15.2–19.5). There were 2 patients with grade 1 cardiotoxicity. Conclusion: Trastuzumab maintenance ± capecitabine after 6 cycles of trastuzumab plus combined chemotherapy treatment revealed efficacy and safety in non-progressive HER2-positive advanced gastric cancer. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.

Introduction: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation.Materials and Methods: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety.Results: Of 163 patients 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13 months disease follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients. Conclusion: Osimertinib is a highly effective option in second or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile.

Background: Immunotherapy improves overall survival (OS) in the second and later lines of renal cell carcinoma (RCC) treatment. Recent studies have suggested that antibiotic (ATB) use either shortly before or after the start of immunotherapy could lead to decreased OS. Herein, we evaluate the impact of ATB use on OS in RCC patients treated with nivolumab in a multi-center cohort from Turkey. Methods: The data of 93 metastatic RCC patients treated with nivolumab in the second line or later were retrospectively collected from 6 oncology centers. Previous treatments, sites of metastases, International Metastatic RCC Database Consortium risk classification, and ATB use in the three months before (-3) or three months after (+3) the start of immunotherapy were recorded together with survival data. The association of clinical factors with OS and progression-free survival (PFS) was analyzed with univariate and multivariable analyses. Results: The median age was 61 (interquartile range 54-67), and 76.3% of the patients were male. The median OS of the cohort was 23.75 ± 4.41, and the PFS was 8.44 ± 1.61 months. Thirty-one (33.3%) patients used ATBs in the 3 months before (-3) or 3 months after (+3) nivolumab initiation. In the multivariable analyses, ATB exposure (HR: 2.306, 95% confidence interval [CI]: 1.155-4.601, P = 0.018) and the presence of brain metastases at the baseline (HR: 2.608, 95% CI: 1.200-5.666, P = 0.015) had a statistically significant association with OS, while ATB exposure was the only statistically significant parameter associated with PFS (HR: 2.238, 95% CI: 1.284-3.900, P = 0.004). Conclusion: In our study, patients with ATB exposure in the 3 months before or 3 months after the start of immunotherapy had shorter OS. Our findings further support meticulous risk–benefit assessments of prescribing ATBs for patients who are either receiving or are expected to receive immunotherapy. WOS:000723830400020 34130864 Q3

Purpose Anaplastic lymphoma kinase (ALK) gene rearrangement exists in approximately 3-7% of non-small cell lung cancer (NSCLC) and more than 15% split or isolated red signals among 50 tumor nuclei scored in the FISH analysis defines as ALK-positive. The previous studies showed that the high EGFR mutational load related to better outcomes in EGFR mutant NSCLC. Therefore, we aimed to investigate the effect of the ALK break-apart ratio on treatment outcome in metastatic ALK-positive NSCLC. Methods The patients (pts) who ALK-positive and treated with crizotinib were retrospectively enrolled. The 30%, 40%, 50%, 60%, and 70% break-apart ratios were determined as a threshold value, and each of these was evaluated separately. Based on the results of these analyses, we detected the optimal threshold value and also performed further investigations. Results A total of 70 patients were enrolled in the study. The most significant decrease in the risk of the progression or death was detected at the 50% threshold value and it was accepted as the optimal threshold. The median PFS was 17.9 vs. 7.06 months (mo) in the pts with high ALK rearrangement than low (HR: 0.43, 95% CI 0.24-0.76, p 0.004). The median OS was also significant longer in high ALK rearrange group (44.6 mo vs. 16.8 mo; HR: 0.37, 95% Cl 0.1883-0.7315; p 0.004). The intracranial progression during crizotinib treatment was significantly frequent in the pts with high ALK rearrangement (62.5-32.5%, P 0.039) Discussion In this study, we found that the high break-apart ratio can predict the extent of benefit from targeted therapy in ALK-positive NSCLC patients. Based on the results of this study, the percentage of the ALK rearrangement can be used to predict treatment outcome and to choose the optimal targeted agent in the treatment of metastatic ALK-positive NSCLC.

Aims: The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience. Materials and Methods: Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed. Results: The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity. Conclusions: Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial. © 2022 Authors. All rights reserved.