In patients with non-liver progression, next-generation ALKis might be the preferred treatment option. and 10.8 months with chemotherapy, respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKis for patients with brain progression (median OS, 28.9 months rearrangement is observed predominantly in younger patients and never or light smokers with adenocarcinoma. Currently, crizotinib is recommended as the first-line standard therapy for inhibitors (ALKis), and chemotherapy. However, the optimal sequential therapy options for specific progression patterns in patients with advanced rearrangement was confirmed by fluorescence hybridization or Ventana immunohistochemistry; progression beyond crizotinib treatment within only one site evaluated by imaging examination; measurable target lesions documented by computed tomography (CT) images of the chest and stomach or magnetic resonance imaging (MRI) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; and a documented Eastern Cooperative Oncology Group performance status (ECOG PS). Patients harboring untreated or treated brain metastases with crizotinib as first-line or second-line crizotinib therapy were eligible. Patients were excluded if they had received any previous ALKi therapy other than crizotinib or had progression in multiple metastatic sites. Smokers were defined as current or former smokers while non-smokers were defined as individuals who had smoked 100 smokes in their lifetime. Non-liver progression defined as other metastatic sites excluding liver and brain metastases. Data were collected from electronic medical records including clinical and survival data. As an observational study, the present study was exempted from obtaining patients informed consent but the study was approved by the institutional Thioridazine hydrochloride review board of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical Thioridazine hydrochloride College. Treatment Patients underwent initial treatment with crizotinib at a dosage of 250 mg twice daily. Continuation of crizotinib beyond disease progression was permitted if the patients clinician had observed clinical benefit. Based on the site of progressive metastases after crizotinib resistance, patients were divided into 3 groups: brain metastases (n=64), non-liver metastases (n=57), and liver metastases (n=17). Sequential therapy mainly included continuation of crizotinib beyond disease progression together with local therapy, next-generation ALKi treatment (ceritinib, alectinib, or Rabbit Polyclonal to PPP4R1L AP26113), and chemotherapy. Patients were permitted to cross over to other therapies if progression occurred during the course of treatment. Outcomes Disease was assessed at baseline after the first dose of study therapy and repeatedly until radiographic progressive disease (PD) was determined by imaging examination, including a CT scan of the chest and stomach or MRI of the brain. Thereafter, scan intervals were about every 2 months. Evaluations of the response included complete response (CR), partial response (PR), stable disease (SD), and PD. Both the objective response rate (ORR), defined as patients showing CR and PR, and disease control rate (DCR), defined as patients showing CR, PR and SD, were calculated. Thioridazine hydrochloride Progression-free survival (PFS) was defined as the time from crizotinib treatment to progressive disease, death or last follow-up. The primary endpoint of the study was median OS from the time of crizotinib resistance to death or the date of the last follow-up (31 December, 2017). Statistical analysis SPSS 16.0 software (SPSS Inc., Chicago, IL, USA) was used for the statistical analyses. Baseline characteristics were presented by applying descriptive statistics. The data for dichotomous variables were presented as the number of patients (n) and percentages (%) and continuous variables were presented as median and range values. The Chi-square test or Fishers exact test was adopted for dichotomous data comparison among groups. The PFS and OS from the time of crizotinib resistance were analyzed using the Kaplan-Meier method. All statistical assessments were two-tailed with P 0.05 considered statistically significant. Variables included.