Comparing survival outcomes for advanced cancer patients who access comprehensive genomic sequencing using a registry-based synthetic control arm.
Authors: O Haire Sophie , Degeling Koen , Franchini Fanny , Tran Ben , Luen Stephen James , Smith Kortnye Maureen , Fox Stephen B. , Desai Jayesh , IJzerman Maarten J. 
Published: June 2021

e18851

Background: Studies evaluating the clinical benefit from Comprehensive Genomic Sequencing (CGS) in cancer patients (pts) have been limited by heterogeneous populations in cancer types and treatment history, outcomes analysis focused on pts who received treatment, and single arm designs. This study evaluated the clinical utility of CGS in a unique real-world advanced cancer patient cohort by comparing a series of pts who received CGS to inform investigational treatment compared to those who did not. Methods: Two cohorts of advanced and refractory pts with diverse cancer types seen for early phase trial consideration were identified from the Peter MacCallum Cancer Centre (PMCC) phase 1 trials clinic. The CGS group (N = 142) accessed an in-house assay on FFPE tissue and matched blood (PMCC Comprehensive Cancer Panel - 391 genes) through a research study between 2017-2018. A second cohort was defined as clinic pts in the following 12 months when profiling was unavailable (NoCGS, N = 133). Difference in overall survival (OS) from initial appointment between the two cohorts was analysed through Kaplan-Meier curves and Cox proportional hazard models. Potential confounding was analysed and adjusted for using stabilised weights based on propensity scores. Results: Within the CGS group, 25 (17.6%) pts received targeted treatment informed by CGS results via trials recruiting at that time (n = 16) or off label drug access (n = 9). This subgroup had improved survival compared with CGS pts in whom results did not alter treatment plan (unadjusted HR = 0.48, (0.27-0.88), p = 0.02). Comparing the CGS and NoCGS cohorts, there were proportional differences in clinical factors including ECOG, cancer types and previous lines of therapy, with standardised differences ranging from 0.23-0.63. Rates of trial participation were similar (CGS: n = 31 [22%], NoCGS: n = 34 [26%]) and CGS had improved unadjusted median OS of 14.5 mos (12.3-19.0) compared to 9.9 (8.6-13.4) for NoCGS (unadjusted HR = 0.71, (0.53-0.96), p = 0.03). In the adjusted analysis, weights ranged from 0.54-2.89 ensuring no individual pts had excessive influence on analysis and resulted in well-balanced populations (range of standardised differences: 0.0-0.09). Adjusted median OS for CGS was 13.5 mos (9.9-17.8) compared to 11.0 (9.2-17.4) for NoCGS (adjusted HR = 0.88, 0.63-1.23, p = 0.50). Conclusions: We utilised real world data in a novel approach to comparative analysis of the clinical benefit of CGS in a heterogenous cancer cohort. Although the subset of CGS pts who went on to receive targeted treatments had improved outcomes, this was insufficient to drive an overall survival gain when considering the overall CGS vs NoCGS cohort. Therefore, translation into clinics requires strategies to ensure a greater proportion of tested pts obtain benefit to deliver on the value proposition of CGS in an advanced cancer population.