Disease	Lung cancer – NSCLC
Stage of Disease/Treatment	Metastatic/advanced
Prior Therapy	1 prior regimen
Type of Study	Phase II, randomized
PFS	p: .0068, HR: 0.3347
Primary Endpoint	Progression‐free survival
Secondary Endpoints	Overall survival, disease control rate, safety
Additional Details of Endpoints or Study Design
Study Design and Eligibility Criteria
This study was a double‐arm, open, multicenter, exploratory clinical study that included patients from six centers in Southeast China. The patients who fulfilled the inclusion criteria were stratified by 2:1 and assigned to the experimental and control groups based on factors such as performance status (PS), presence or absence of brain metastasis, and histological type.
The specific inclusion criteria were as follows: locally advanced or advanced primary NSCLC diagnosed by histology or cytology (account to American Joint Committee on Cancer version 7 stage, stage IIIB with unresectable, stage IV) that could not be surgically resected or recurred; age ≥18 years and ≤75 years; no epidermal growth factor receptor–sensitive mutations detected by molecular pathology; negative of anaplastic lymphoma kinase, or unknown; and had experienced progression of disease after chemotherapy or had discontinued therapy owing to intolerable adverse effects. Other inclusion criteria were as follows: at least one measurable lesion; Eastern Cooperative Oncology Group (ECOG) score 0–1; estimated survival time ≥3 months; and adequate hematologic, hepatic, and renal function. Patients with asymptomatic brain metastases were also included. Patients with uncontrolled blood pressure on medication (>140/90 mmHg), those with bleeding tendency, and those receiving thrombolytics or anticoagulants were excluded. The study was approved by the ethics committee. All patients provided written informed consent before participation in the study.
Study Assessments
The baseline assessment of the tumor was performed within 28 days prior to enrollment. Measurable lesions were determined by computed tomography (CT) or magnetic resonance imaging (MRI), followed by radiographic evaluation after every two cycles of treatment until disease progression. Efficacy was evaluated according to the RECIST standards (version 1.1) and divided into complete remission (CR), partial remission (PR), stable disease (SD), and progression of disease (PD). The adverse events were defined and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (version 4.03) and observed and evaluated at the beginning of the treatment as well as after 28 days. The primary research endpoint was PFS, whereas the secondary endpoints were total OS, DCR, and safety.
Statistical Analyses
Patients were stratified based on ECOG PS, presence or absence of brain metastasis, gender, smoking history, and histological type. In analyzing the data, we performed exploratory analyses comparing the two treatment arms. The primary research endpoint was PFS, whereas the secondary endpoints were OS, DCR, and safety. Between‐group differences in patient characteristics were analyzed using the t test. The differences before and after treatment were determined by analysis of variance or the rank sum test. Median PFS and OS were estimated from Kaplan‐Meier curves.
As to study design and size, this was an investigator‐initiated exploratory study. Referring to the results of the LUME‐Lung 1 trial, the control group of PFS was set to 2.7 months, and the experimental group of PFS was assumed to be 5.2 months. The unilateral threshold value and test efficacy was set to 10% and 80%, respectively, and 49 patients (33 in the experimental group and 16 in the control group) were scheduled to be enrolled. Owing to the geographical and epidemiological factors of the disease, the enrollment was slow and exceeded the expected enrollment time. We terminated the study when 37 patients were enrolled.
Investigator's Analysis	Active and should be pursued further