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

Efficacy and tolerability of vismodegib treatment in locally advanced and metastatic basal cell carcinoma: retrospective real-life data.

The study aims to evaluate the vismodegib treatment in local advanced (laBCC) and metastatic (mBCC) basal cell carcinoma. The data of 29 patients were retrospectively reviewed. The clinical and histopathological features of the patients and adverse events of vismodegib were recorded. Overall survival (OS) and progression-free survival (PFS) were evaluated with Kaplan-Meier analysis. The median follow-up period was 17 months (range: 1.6-57.3), and the median age at diagnosis 73 years (range: 39-88). The most common disease location was head and neck (86.2%), and the most common non-skin sites of disease were lymph nodes (13.8%), bone (13.8%), lung (6.9%), and brain (6.9%). Three (10.3%) patients had Gorlin's syndrome. The number of metastatic patients was 5 (17.2%). With vismodegib treatment, the complete response rate was 27.6%, partial response 55.2%, and stable response 10.3%. Treatment responses were most frequently seen within 2 months from the beginning of vismodegib. The median OS was 43.3 +/- 9.0 months (25.6-61.1) for all patients. The median PFS in the laBCC was 15.7 +/- 1.8 months (12.2-19.3), and 12.1 +/- 4.6 months (2.9-21.2) in the mBCC. In the univariable analysis for the OS, only the treatment after the vismodegib was statistically significant, showing chemotherapy was better comparing to no treatment or surgery. The most common adverse events were fatigue-58.6%, muscle spasms-48.3%, alopecia-13.8%, and weight loss-13.8%. This real-life data study shows that vismodegib treatment in locally advanced and metastatic BCC was well tolerated and effective

Immunoglobulin V(D) J recombination, protein ubiquitination, cell adhesion and sonic hedgehog gene variants are detected among familial multiple myeloma subjects following whole exome sequencing

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The relationship between clinicopathological parameters and PD-L1 expression level in advanced stage non-small cell lung cancer

Introduction: Clinicopathological parameters related to programmed death ligand 1 (PD-L1) expression levels have been investigated in several studies. However, the results of these studies are conflicting and vary in different populations. This study aimed to investigate the relation of clinicopathological parameters with PD-L1 expression level in advanced stage non-small cell lung cancer patients

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

Purpose Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-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 first-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 effects were common and toxicities were manageable. Conclusion This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC