Current guidelines in non-small cell lung cancer recommend genomic assessment for mutations in EGFR and BRAF, gene rearrangements in ALK and ROS1, and resistance mutations such as T790M upon progression during EGFR inhibitor therapy. However, obtaining sufficient tumour tissue to test for these molecular alterations, as well as those with emerging targeted therapies, is challenging in lung cancer. A promising method to improve molecular diagnostic testing in lung and other cancers is the use of circulating cell-free DNA (cfDNA) obtained from blood samples or liquid biopsies. This multi-centre prospective study will compare blood-based profiling (using the GUARDANT360 assay) to standard of care tissue-based profiling within the Canadian system.
Name: GUARDANT360
Description: Measure best response to first-line therapy using investigator-assessed RECIST 1.1, including progression free survival and time to treatment failure, in patients with advanced lung adenocarcinoma using the cfDNA GUARDANT360 assay versus standard of care tissue genotyping.
Measure: Response rate to first-line therapy Time: Up to 18 MonthsDescription: Compare the proportion of patients receiving targeted therapy using the cfDNA GUARDANT360 assay versus standard of care tissue genotyping.
Measure: Proportion of patients receiving targeted therapy Time: Up to 18 MonthsDescription: The time to treatment initiation using both genotyping methods, will be calculated as the number of days from the date of pathologic or clinical stage IV NSCLC diagnosis until initiation of systemic treatment. This will be compared to the turnaround time for GUARDANT360 results.
Measure: Time to Treatment Initiation Time: Up to 18 MonthsDescription: Count the number of actionable genomic alterations identified in cfDNA that were not identified in tumour tissue standard of care testing.
Measure: Incremental number of actionable genomic alterations Time: Up to 18 MonthsDescription: Calculate the time (in days) from the date of request for testing to the report date for both genotyping methods.
Measure: Turnaround time of cfDNA vs. tissue results Time: Up to 18 MonthsDescription: Cost consequence analysis to examine incremental mean direct and indirect costs in Canadian dollars between the two approaches (cfDNA testing vs tumour tissue genotyping).
Measure: Costs of cfDNA vs. tissue testing Time: Up to 18 MonthsDescription: Assess response rate in patients (Cohort 1) who received single agent or combination immunotherapy.
Measure: Response rate to immunotherapy Time: Up to 18 MonthsDescription: Assess response duration in patients (Cohort 1) who received single agent or combination immunotherapy.
Measure: Response duration to immunotherapy Time: Up to 18 MonthsDescription: Patient quality of life will be measured using the EQ5D-5L, which will be administered upon entry to the study and 3 months after starting systemic therapy.
Measure: Patient reported quality of life Time: Upon entry and 3 months following initiation of systemic therapyDescription: Evaluate patient willingness-to-pay for using a next generation sequencing assay, such as the GUARDANT360, using a validated patient survey.
Measure: Patient willingness-to-pay Time: Within 30 days of study enrollmentCohort
There is one SNP
Achieving Value in Cancer Diagnostics: Blood Versus Tissue Molecular Profiling - a Prospective Canadian Study Current guidelines in non-small cell lung cancer recommend genomic assessment for mutations in EGFR and BRAF, gene rearrangements in ALK and ROS1, and resistance mutations such as T790M upon progression during EGFR inhibitor therapy. --- T790M ---
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. --- T790M ---
Patients progressing on 1st or 2nd generation EGFR TKI must have undergone SOC testing for EGFR T790M. --- T790M ---
If blood- or tissue-negative for T790M, the patient is eligible for this study. --- T790M ---
If T790M-positive, the patient must have progressed on a T790M inhibitor to be eligible. --- T790M ---
If T790M-positive, the patient must have progressed on a T790M inhibitor to be eligible. --- T790M --- --- T790M ---