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:

• Histologically-proven, advanced (Stage IIIB or IV not eligible for curative intent treatment, or relapsed/recurrent) disease;
• Non-squamous histology (mixed adenocarcinoma histology is allowed);
• Never smoking or light smoking history (≤10 pack years);
• Measureable disease by RECIST 1.1;
• 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;
• Age ≥ 18 years;
• Ability to provide written informed consent;
• Agreement to provide blood sample prior to starting systemic treatment;
• Eligibility for targeted therapy in the opinion of the investigator;
• Standard-of-care tissue genotyping ordered or planned. Patients with tissue deemed insufficient for genotyping are eligible.
• 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

• Pregnancy;
• ≥10 pack year smoking history;
• 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;
• Prior resection of metastatic disease if the resected metastasis was the only site of measurable disease;
• Radiation of a metastatic lesion or residual disease if administered to the only site(s) of advanced disease;
• 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.