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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 (

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

© 2021 Taylor & Francis Group, LLC.Purpose: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2−) metastatic breast cancer (MBC) patients in real-life settings. Methods: Overall, 204 HR+, HER2− MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. Results: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). Conclusion: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER − MBC patients.

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.

Increasing use ofThe objective of this study was to assessA total of 6500 patients followed-up in a single and tertiary center between January 2010 and September 2016 were retrospectively reviewed. Of 2850 patients assessed withOf 658 patients withAlthough this study demonstrated high probability of malignant disease with increased

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.

Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin. In this study, we aimed to evaluate the clinicopathologic characteristics, treatment outcomes, and survival of MCC cases in Turkey. Materials and methods: The patients diagnosed with MCC between 1999 and 2018 at twenty different centers in Turkey were included in the study. Patient and tumor characteristics and adjuvant and metastatis treatment outcomes were analyzed retrospectively. Results: The median age of totally 89 patients was 70 (26-93). The most common primary location was lower limbs (n = 29, 32.5%). Immunohistochemically, CK20 positivity was present in 59 patients (66.3%). Only two patients had secondary malignancy. The majority of the patients (n = 76, 85.4%) were diagnosed at the localized stage. Surgery was performed for all patients in the early stage, and adjuvant radiotherapy or/and chemotherapy was applied to 52.6% (n = 40) of nonmetastatic patients. The median follow-up was 29 months. Recurrence developed in 21 (27.6%) of the 76 patients who presented with local or regional disease. Two-year disease-free survival (DFS) was 68.1% and 5-year DFS was 62.0% for localized stage. The 5-year DFS was similar for patients receiving adjuvant treatment (chemotherapy, radiotherapy, or sequential chemoradiotherapy) and without adjuvant therapy (P > 0.05). Two-year overall survival in patients who presented with localized disease was 71.3% and 18.5% in metastatic patients (P < 0.001). In the metastatic stage, platinum/etoposide combination was the most preferred combination regimen. Median progression-free survival (PFS) in first-line chemotherapy was 7 months (95% confidence interval: 3.5-10.5 months; standart error: 1.78). Conclusions: Although MCC is rare in Turkey, the incidence is increasing. Gender, CK20 status, tumor size, lymph node involvement, and adjuvant treatment were not associated with recurrence.

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.

Purpose: Colorectal cancer is the third leading diagnosis accounting for nearly 10% of all new cancers worldwide. The distinct features among BRAF mutant colorectal cancers make these tumor groups hard to treat for oncologists. The median overall survival (OS) of these types of cancers is reported to be 9 to 14 months. Methods: The study was declared on the Turkish Oncology Study Group Conference and approved. The patients’ data was received from the centers who confirmed to participate. The BRAF-mutated patients were included in the study. The demographic features (age, gender, etc.), type of mutation, tumor localizations, histology, microsatellite instability (MSI) status, metastasis patterns chemotherapeutic agents and progression, and death times were recorded. Results: Thirty-nine patients were enrolled in the study. Sixteen patients had concurrent KRAS mutations, while 7 had NRAS mutations. Most of the patients received doublet chemotherapies in combination with anti-VEGF agents in the first and second line of the treatment. There was a significant difference in OS according to the stage which showed a decreased survival in stage IV patients at the time of diagnosis. Concurrent KRAS mutation resulted in increased OS. The median OS was 47 and 24 months favoring the KRAS mutant group. The patients whose primary tumor operated had better survival when compared with other patients. The median OS of the operated group was 47 months, while the non-operated group was 24 months. Liver metastasis was related to worse prognosis at the time of diagnosis in univariate analysis. Conclusion: In our study we found a high concurrent RAS mutation ratio in a BRAF mutant patient group which was different from prior studies. The concurrent mutations resulted in a favorable outcome in terms of OS which is also different from the current knowledge. More prospective studies are needed especially BRAF-mutated patient population and especially with concurrent RAS mutations. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients.In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study.The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007).Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.

The purpose of this study was to determine the influence of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) on antiEGFR and bevacizumab efficacy in metastatic colorectal cancer patients.All metastatic colorectal cancer patients who had received chemotherapy and biological agents as first-line treatment at Erciyes University Hospital were retrospectively reviewed. NLR and PLR were each divided into two groups, as high and low. The NLR high group was compared with the low group and the PLR high group was compared with the low group in patients in terms of progression-free survival (PFS) and overall survival (OS), separately. Cox regression and the Kaplan Meier method were used.One hundred and thirty (58%) of the patients had received bevacizumab and 94 (42%) had received antiEGFR therapy (cetuximab or panitumumab). In the bevacizumab group, PFS was 9 months in the NLR high group and 11 months in the NLR low group (p=0.013). OS was 23 months in the NLR high group and 27 months in the NLR low group (p=0.734). There was no statistically significant OS difference in patients who had received antiEGFR therapy according to NLR. There was no statistically significant PFS difference in patients who received bevacizumab according to PLR. In the antiEGFR group, PFS was 9 months (95% CI, 8.07-13.55) in the PLR high group and 18 months (95% CI, 12.02-18.68) in the PLR low group, with statistically significant difference (p=0.040). There was no statistically significant OS difference in patients who had received antiEGFR therapy according to PLR.NLR and PLR are important inflammatory markers. In patients who had received bevacizumab, PFS was longer in the NLR low group than in the high group. In patients who had received antiEGFR, PFS was longer in the PLR low group than in the high group.

*Şakalar, Teoman ( Aksaray, Yazar ), Purpose: We aimed to assess the prognostic and predictive significance of pretreatment Onodera’s prognostic nutritional index (OPNI) in metastatic non-small cell lung cancer patients (NSCLC) treated with first-line chemotherapy. Materials and methods: Patients with metastatic NSCLC who attended five different medical oncology clinics between December 2008 and January 2018 were retrospectively analyzed. The optimal cut-off point for OPNI was performed by a receiver operating characteristic (ROC) curve analysis. Patients were assigned to either the low OPNI group or high OPNI group. Results: A total of 333 patients were included in the study. Significant differences between the low and high OPNI groups were found regarding the rates of response to chemotherapy, sex, and hemoglobin level (p < 0.05). The patients in high OPNI group had a longer overall survival (OS) (15.3 vs. 10.6 months, p < 0.001) and progression-free survival (PFS) (6.7 vs. 5.3 months, p < 0.001) compared to the patients in low OPNI group. A multivariate analysis using Cox regression model revealed that a high OPNI score was an independent prognostic factor of OS (HR = 1.535, p = 0.002) and PFS (HR = 1.336, p = 0.014), but failed to demonstrate a statistical significance of pretreatment OPNI scores in predicting treatment response (p = 0.56). Conclusions: Pretreatment OPNI is an independent prognostic factor for OS and PFS in metastatic NSCLC patients treated with first-line chemotherapy. Thus, it may be used as easily calculated and low-cost prognostic tool in the routine clinical practice in this patient group.

Non-small-cell lung cancer (NSCLC) constitutes 80-85% of all lung cancers. Patients with advanced-stage NSCLC may benefit from chemotherapy. Gemcitabine and cisplatin is a well-established therapy for this malignancy. Recently, biweekly administration is becoming more acceptable, but the most effective and tolerable dose remains unclear. The purpose of this study was to compare the toxicity and efficacy of 1000 mg/mGemcitabine was administered at a dose of 1000 or 1500 mg/m114 patients with IIIB and IV stages of NSCLC were included. Seventy two patients (63%) received GEM 1000 and 42 (37%) received GEM 1500. The overall reponse rate (ORR), PFS and OS were 24%, 6 months and 13 months respectively in the GEM 1000 group and 36%, 6 months and 15 months in the GEM 1500 group, respectively. Grade 3-4 neutropenia and thrombocytopenia were observed in 4% of the GEM 1000 group and 9% of the GEM 1500 group (p=0.41).Biweekly administration of GEM 1000 and 1500 is a well tolerated regimen. Although the GEM 1000 group showed a lower response rate than the GEM 1500 group, PFS and OS were similar.