Crizotinib efficacy and safety in patients with advanced NSCLC harboring MET alterations: A real-life data of Turkish Oncology Group

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

Retrospective evaluation of patients diagnosed toxic hepatitis and assessment of the findings laboratory values, liver biopsy results and medical procedures

TOKSİK HEPATİT TANISI ALAN HASTALARDA LABORATUAR DEĞERLERİ, KARACİĞER BİYOPSİ SONUÇLARI VE YAPILAN TIBBİ İŞLEMLERİN RETROSPEKTİF DEĞERLENDİRİLMESİ Karaciğer ilaçlar ve çeşitli egzojen toksinlerin metabolizması için elzemdir. Bundan dolayı, doğal, evsel, endüstriyel toksinler, ilaçlar ve mantarlar nedeniyle karaciğer toksisitesine sık rastlanmaktadır, ancak daha nadiren tanı almaktadır. Çalışmamızda analizlere dahil edilen veriler içerisinde, beyaz küre sayısı (WBC), nötrofil sayısı, alanin aminotransferaz (ALT), aspartat aminotransferaz (AST), alkalen fosfataz (ALP), gama glutamil transferaz (GGT), laktat dehidrojenaz (LDH), albümin, INR, total ve direkt bilurubin yer almaktaydı. Bunlara ek olarak, karaciğer biyopsisi sonuçları, uygulanan tedaviler (plazmaferez, hemodiyaliz, transplantasyon) ve mortalite oranı değerlendirildi.Hastaların toksik karaciğer hastalığı nedenleri ilaçlar, bitkisel ürünler, ilaçlar, mantarlar ve bilinmeyen olarak sınıflandırıldı. Karaciğer hasarı paterni, ALT ve ALP seviyeleri kullanılarak hepatoselüler, kolestatik ve mikst tip olarak sınıflandırıldı. En sık toksik hepatit nedeni %48.8 ile ilaçlardı. Bunu mantar (%20.8), herbal (%18.8) ve uyuşturucu madde (%3.0) toksikasyonu izlemekteydi. Vakaların %8.6'sında ise etiyoloji bilinmiyordu.Toksik hepatite neden olan en sık ilaçlar sırasıyla NSAİ (%31.1), antibiyotikler (%21.6), antitüberküloz ilaçlar (%6.8), antiepileptikler (%6.8) ve parasetamoldu (%6.1). Hastaların %18.5'ine (n=56) karaciğer biyopsisi yapılmıştı. Histopatolojik incelemelerde, bu hastaların %92.9'unda karaciğer nekrozu, %60.7'sinde eozinofili, %67.9'unda hidropik karaciğer dilatasyonu, %28.6'sında ise safra tıkacı izlenmişti. Karaciğer hasarı paterni hastaların %25.1'inde kolestatik tip, %28.7'sinde mix tip, %46.2'sinde hepatoselüler tipti. Tedavide hastaların %13.2'sinde plazmaferez, %13.2'sinde diyaliz, %2.3'ünde ise karaciğer nakli tercih edilmişti. Genel mortalite oranı %6.3'tü. Sonuç olarak hastaların %8.2'si (n=25) kaybedilmişti veya karaciğer nakli yapılmıştı (ex/nakil). Anahtar kelimeler: Toksik karaciğer hastalığı, İlaca bağlı, Mantar, Bitkisel, Narkotik, Mortalite, Hasar paterniRetrospective evaluation of patients diagnosed toxic hepatitis and assessment of the findings laboratory values, liver biopsy results and medical procedures The liver is essential for metabolism of drugs and exogenous toxins. Therefore, liver toxicity due to natural, domestic and industrial toxins, mushroom or drugs is common but rarely recognised. The study was evaluated white blood cell (WBC), neutrophil count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), albumin, INR, total and direct bilirubinwere included in the analyzes. Moreover, liver biopsy results, treatments (plasmapheresis, hemodialysis, transplantation) and mortality ratewere evaluated.The causes in the etiology of toxic liver disease of the patients were classified as drugs, herbal products, drugs, mushroom and unknown. The liver damage pattern was classified as hepatocellular, cholestatic and mixed type using ALT and ALP. The most common cause of toxic hepatitis was drugs with 48.8%, followed by mushroom (20.8%), herbal (18.8%) and narcotic (3.0%) toxicity. Etiology was unknown in 8.6% of cases.The most common drugs causing toxic hepatitis were NSAID (31.1%), antibiotics (21.6%), antituberculosis drugs (6.8%), antiepileptics (6.8%) and paracetamol (6.1%). 18.5% of the patients (n = 56) underwent liver biopsy. Histopathological examinations showed liver necrosis in 92.9%, eosinophilia in 60.7%, hydropic liver dilatation in 67.9% and bile obstruction in 28.6%. Liver damage patern was hepatocellular type in 46.2%, cholestatic type in 25.1%, mix type in 28.7%. Plasmapheresis was preferred in 13.2% of patients, dialysis in 13.2% and liver transplantation in 2.3%. Overall mortality rate was 6.3%. 8.2% (n = 25) of patients were died or transplanted. Key words:Toxic liver disease, Drug-induced, Mushroom, Herbal, Narcotics, Mortality, Injury pater

Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

Background There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and >= 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET