......

...Patients who have failed after at least two systemic chemotherapy (EGFR mutations and ALK/ROS1 positive patients also need to undergo progression after the corresponding targeted therapy); 5. ...

...1.Patients voluntarily participated in the study and signed informed consent; 2.Age > 18 years old, both male and female; 3.Patients with locally Advanced or metastatic (stage III B, III C or IV) NSCLC confirmed by histology or cytology, and EGFR 19del and / or 21 L858R mutations were detected by NGS,and asymptomatic brain metastases can be enrolled; 4.According to the evaluation criteria of solid tumor efficacy (RECIST1.1), one measurable lesion can be used as the target lesion at least; 5.PS score 0~3; 6.Expected survival time>= 3 months; 7.Patients who had not previously received systematic antitumor therapy, including radiotherapy and chemotherapy, targeted and immunotherapy....

...1) patients voluntarily participated in the study and signed informed consent; 2) the late stage (stage IIIB/IV) non-small cell lung cancer diagnosed by pathology has measurable lesions; 3) Patients with EGFR gene-sensitive mutations who received first-generation EGFR-TKI therapy were assessed by imaging for slow progression; 4) ddPCR method was used to detect T790M mutation negative patients; 5) gene detection of ALK gene test negative results; 6) Aged 18-75 years old; ECOG PS score 0~2; and the expected survival is more than March; 7) no major abnormalities in organ function....

...Mutation status including EGFR, ALK ROS are explicit; 5. ...

...- Patients who has failed from the first-line Platinum-based Doublet chemotherapy harbouring epidermal growth factor receptor(EGFR) sensitive mutations negetive, confirmed by pathological or blood test results) ）,ALK/ROS1 mutation-negative or unknown (For recurrent patients, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility, and the last treatment time must be more than 6 months before enrollment）...

...For patients with EGFR mutation or ALK mutation positive, amlotinib should be used after progression after receiving the corresponding targeted drug therapy and progression or recurrence after at least 2 systemic chemotherapy; 5. ...

...It can provide high-throughput tumor gene detection reports including EGFR mutation sites and mutation abundance, or provide tumor tissue samples for flux tumor gene detection. ...

...1) Aged 18-75 years male and female; 2) Pathologically confirmed stage IV NSCLC; 3) ECOG PS score: 0-2; 4) Patients with negative driving genes were evaluated for progression or intolerance after at least two different regimens of chemotherapy, or patients with positive driving genes (EGFR mutation or ALK rearrangement) were evaluated for progression or intolerancetreated after the treatment of TKI and at least one regimen of chemotherapy; 5) According to RECIST, patients have measurable lesions; 6) The estimated survival time is more than 12 weeks; 7) With well main organs function; 8) Hemoglobin (>100 g/L); Platelet count > 100 *10^9/L; The number of neutrophils more than 1.5 x 10^9/L; 9) serum creatinine ≤1.25×ULN, or creatinine clearance rate > 60 mL/min; 10) TBIL ≤1.5× ULN; AST (SGOT) and ALT（SGPT）≤2.5×(ULN), Alkaline phosphatase ≤ 5×ULN; 11) No interstitial pneumonia or previous history of interstitial pneumonia; 12) Patients or family members signed the informed consent....

...Subjects with histologically or cytologically confirmed locally advanced or advanced NSCLC who have previously received one lines chemotherapy, EGFR TKI or ALK inhibitor (whom with EGFR or ALK mutation but...

...- No-drive gene mutaion (EGFR、ALK、ROS1） by NGS...

...- EGFR mutation-positive、ALK mutation-negative；Patients have progressed after receiving EGFR targeted and chemotherapy as first-line treatment....

...- Histologically confirmed that EGFR sensitive mutation (ex19del or L858R mutation) in tumor tissue was detected by non-squamous NSCLC, and EGFR mutation (ex19del or L858R mutation) in ctDNA before treatment;...

...- Epidermal Growth Factor Receptor(EGFR)mutations confirmed by molecular detection (including, but...

...EGFR、ALK、ROS1 mutation-negative；Patients with squamous cell carcinoma may...

...- 5.Documented evidence of tumor harboring an activating EGFR mutation (exon19 del and L858R)...

...- The patients should be confirmed with EGFR mutation [e.g., T 790 M , exon 19 deletion, L 858 R, etc],...

...- Previously, EGFR gene test showed EGFR exon 19 deletion or exon 21 (L858R) mutation, and the gene test showed...

...- EGFR、ALK、ROS1 mutation-negative；Patients with squamous cell carcinoma may...

...- Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R)...

...- EGFR mutations confirmed by molecular detection (including, but...

...- EGFRALKROS1 wildtype or unknown,or patients with EGFRALKROS1 mutations but refuse to receive corresponding inhibitors' treatment...

...Mutation status including EGFR, ALK ROS are explicit; 5....

...- Epidermal Growth Factor Receptor(EGFR)mutations confirmed by molecular detection (including, but...

...- Patients with EGFR、ALK、ROS1 Mutation-negative were eligible....

...Patients with negative driver genes who have received at least one type of systemic chemotherapy (including combined immune checkpoint inhibitors or anti-vascular drug therapy) have progressed, relapsed, or become intolerable; Patients with positive driver gene (EGFR mutation or ALK fusion positive) who have progressed, relapsed, or become intolerable after receiving corresponding standard targeted drug therapy; 3. ...

...Pathology diagnosed with stage IV NSCLC with no driver oncogene who have failed for second lines of therapy; Pathology diagnosed with stage IV NSCLC with EGFR mutation positive and T790M negative who had rapid progression after first-line targeted therapy and not wiling to accept chemotherapy; or stage IV NSCLC with EGFR mutation positive patients who had progression after second-line targeted therapy; 2. ...

...Histological diagnosis of EGFR mutation-positive IIB(not suitable for surgery or radiotherapy) to stage IV non-small cell lung cancer; 4. ...

The EGFR–TKI + anlotinib therapy exhibited an objective response rate of 20.8% and a disease control rate of 95.8%. Median progression-free survival (PFS) was 11.53 ± 2.41 months...Concurrent use of anlotinib overcomes acquired resistance to EGFR-TKI in advanced EGFR-mutant NSCLC patients.

Sixty-seven patients with previously treated advanced NSCLC receiving anti-PD-1 agents concomitant with anlotinib...The benefit of anti-PD-1 plus anlotinib was also observed in patients with EGFR mutation positive, liver metastases and brain metastases.

Advanced NSCLC patients progressed during or after platinum-based doublet chemotherapy were assigned to treat with docetaxel at a dose of 60mg per square meter of body-surface area and anlotinib at a dose of 12mg oral per day...4 (16.0%) patients harbored with EGFR mutation or ALK fusion...PFS was 4.5 months (95% CI, 3.5-5.5). The ORR was 7/20(35.0%), stable disease was 12/20(60.0%), DCR was 19/20(95.0%) and progress disease was 1/20(5.0%).

Of 437 pts, 138 (31%) exhibited EGFR mutations and 299 (69%) presented WT. Anlotinib provided more benefit in OS on mutant EGFR pts than WT pts (table 1)...Anlotinib presented significant improvement in OS on pts with refractory disease (resistant to 1st-generation TKI) of mutant EGFR comparing WT EGFR.