Achieving Value in Cancer Diagnostics: Blood Versus Tissue Molecular Profiling - a Prospective Canadian Study

Inclusion Criteria: Patients with non-small cell lung cancer (NSCLC) with: 1. Histologically-proven, advanced (Stage IIIB or IV not eligible for curative intent treatment, or relapsed/recurrent) disease; 2. Non-squamous histology (mixed adenocarcinoma histology is allowed); 3. Never smoking or light smoking history (≤10 pack years); 4. Measureable disease by RECIST 1.1; 5. Patients who have previously received curative therapy are eligible if primary treatment was completed at least 6 months prior to the development of advanced disease; for patients who received adjuvant systemic therapy, the last dose of treatment must have been given at least 6 weeks prior to enrollment; 6. Age ≥ 18 years; 7. Ability to provide written informed consent; 8. Agreement to provide blood sample prior to starting systemic treatment; 9. Eligibility for targeted therapy in the opinion of the investigator; 10. Standard-of-care tissue genotyping ordered or planned. Patients with tissue deemed insufficient for genotyping are eligible. 11. Cohort 2 only: evidence of disease progression on prior targeted tyrosine kinase inhibitor or other targeted therapy for EGFR including T790M, ALK, ROS-1 or BRAF-deranged advanced NSCLC. Patients progressing on 1st or 2nd generation EGFR TKI must have undergone SOC testing for EGFR T790M. If blood- or tissue-negative for T790M, the patient is eligible for this study. If T790M-positive, the patient must have progressed on a T790M inhibitor to be eligible. Intervening systemic therapy such as chemotherapy or immunotherapy is permitted. Exclusion Criteria: 1. Pregnancy; 2. ≥10 pack year smoking history; 3. Any other concurrent malignancy except for localized, non-melanoma, cutaneous cancer or non-invasive cervical cancer. Any prior cancer other than NSCLC must have occurred more than 2 years prior to study entry with no evidence of currently active disease; 4. Prior resection of metastatic disease if the resected metastasis was the only site of measurable disease; 5. Radiation of a metastatic lesion or residual disease if administered to the only site(s) of advanced disease; 6. Cohort 1 only: Prior systemic treatment for metastatic NSCLC including but not limited to targeted therapy, chemotherapy, immunotherapy, or biologic therapy. Adjuvant therapy is permitted at least 6 weeks prior to enrollment.