Primary Outcomes

Description: The proportion of patients that are progression-free according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

Measure: progression free rate (PFR)

Time: 4 months from recruitment

---

Secondary Outcomes

Description: The proportion of patients with negative biomarker that are progression-free according to RECIST 1.1

Measure: progression free rate (PFR) in biomarker negative sub-cohort

Time: 4 months from recruitment

---

Description: The difference of PFS between biomarker positive and biomarker negative sub-cohorts with log-rank test

Measure: progression free survival(PFS) between biomarker positive and negative sub-cohorts

Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

---

Description: Correlation of KDR 604 AA，AG，GG genotype with the incidence of pulmonary lesion cavitation or pneumothorax among all comers

Measure: Correlation of KDR polymorphism with pulmonary lesion cavitation/pneumothorax

Time: 4 months from recruitment

---

Description: Correlation of KDR 604 AA，AG，GG genotype with the incidence of hair depigmentation among all comers

Measure: Correlation of KDR polymorphism with hair depigmentation

Time: 4 months from recruitment

---

Description: Correlation of KDR 604 AA，AG，GG genotype with progression free survival according to RECIST 1.1 among all comers

Measure: Correlation of KDR polymorphism with progression-free survival(PFS)

Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

---

Description: The occurrence of each adverse events(AEs), severe AEs(SAEs) and death according the CTCAE_5.0

Measure: Incidence of Treatment-Emergent Adverse Events

Time: through study completion, an average of 8 months

---

Description: Correlation of CSF1R (rs10079250) genotype with the incidence of wound complications among all comers

Measure: Correlation of CSF1R polymorphism (rs10079250) with wound complication

Time: through study completion, an average of 8 months

---

Description: Correlation of PDGFRα (rs35597368) genotype with the incidence of hand foot skin reaction among all comers

Measure: Correlation of PDGFRα polymorphism (rs35597368) with hand foot skin reaction

Time: through study completion, an average of 8 months

---

Description: to correlate the incidence of targeted therapy related AEs （pulmonary lesion cavitation, pneumothorax, hair depigmentation) with the PFS

Measure: Early identification of AEs as predictive biomarker

Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

---

Other Outcomes

Description: The PFS for each subgroups in terms of clinicopathological characteristics (age, gender, histological type, solitary or multiple metastases, unilateral or bilateral metastases, early or late metastases, calcifying or non-calcifying lesions, with or without lesion cavitation, with or without AEs [especially pneumothorax, hand-foot skin reactions, hair depigmentation], etc

Measure: Exploratory outcome: Subgroup analysis of progression-free survival(PFS)

Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

---

Description: To explore the molecular basis underlying the difference of biomarker positive and negative sub-cohorts using next generation sequencing

Measure: Exploratory outcome: the molecular analysis of tumor sample

Time: through study completion, an average of 8 months

---

Description: to compare the growth pattern/ distribution of pulmonary versus extrapulmonary lesion at baseline and at disease progression between the two sub-cohorts

Measure: Exploratory outcome: the pattern of disease progression between the sub-cohorts

Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

---

Description: to compare the diagnostic value of the 1.0 mm versus 5.0 mm CT scan for the radiological evaluation of small lung nodule as tumor recurrence

Measure: Exploratory outcome: 1.0-mm CT scan for pulmonary assessment

Time: Baseline until disease progression or death, whichever occurs first, assessed for an average of 8 months

---