Comparing Survival Outcomes for Advanced Cancer Patients Who Received Complex Genomic Profiling Using a Synthetic Control Arm

Abstract

Background Complex genomic profiling (CGP) has transformed cancer treatment decision making, yet there is a lack of robust and quantifiable evidence for how utilisation of CGP improves patient outcomes. Objective This study evaluated cohort level clinical effectiveness of CGP to improve overall survival (OS) in real-world advanced cancer patients using a registry-based matched control population. Patients and methods Two cohorts of advanced and refractory cancer patients were seen in consecutive series for early phase trial enrolment consideration. The first cohort (CGP group) accessed tumour profiling via a research study; while the second cohort that followed was not profiled. Overall survival between cohorts was compared using 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 CGP group, 25 (17.6%) patients received treatment informed by CGP results and this subgroup had significantly improved survival compared with CGP patients in whom results did not impact their treatment (unadjusted HR = 0.44, (0.22–0.88), p = 0.02). However, when comparing the entire CGP cohort with the No CGP cohort, no significant survival benefit was evident with adjusted median OS for CGP of 13.5 months (9.2–17.0) compared with 11.0 (9.2–17.4) for No CGP (adjusted HR = 0.92, (0.65–1.30), p = 0.63). Conclusions This study utilised real-world data to simulate a control arm and quantify the clinical effectiveness of genomic testing. The magnitude of survival benefit for patients who had CGP result-led treatments was insufficient to drive an overall survival gain for the entire tested population. Translation of CGP into clinics requires strategies to ensure higher rates of tested patients obtain clinical benefit to deliver on the value proposition of CGP in an advanced cancer population. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-022-00910-0.

Examining external control arms in oncology: A scoping review of applications to date

“…encountered a comparable gap, where the treatment arm data were collected from October 2008 to May 2012, while the ECAs data spanned from January 2005 to October 2008 47 . A more substantial temporal gap was evident in the study conducted by O'Haire et al., with nearly a 7‐year period between the treatment arm (May 2015–August 2017) and the ECAs data (November 2008–November 2015) 28 …”

“…Pooled data from past trials were the primary data sources used in constructing the ECAs, featured in 30% (7/23) of the studies. 26,41,45,46,48,51,53 Administrative health databases 28,38,39,47 and electronic medical records 34,36,44,49 T A B L E 1 (Continued) from registries 37,50,52 , and 4% (1/23) did not specify the data source. 42 Moreover, 13% (3/23) drew from external databases, 33,35,43 while an equal percentage 4% (1/23) collected from both administrative health databases and registries 40 (Table 1).…”

Clinical Impact of Comprehensive Molecular Profiling in Adolescents and Young Adults with Sarcoma

“…WGTS was performed according to our previously described methodology [8]. TS was performed using either the TruSight Oncology 500 Assay (Illumina) or an in-house-developed tumour-normal comprehensive targeted DNA panel test [9,10]. Both TS assays are designed to detect selected fusions.…”

First-Line Genomic Profiling in Previously Untreated Advanced Solid Tumors for Identification of Targeted Therapy Opportunities

“…Furthermore, some patients who had completed the standard treatment could not enroll in the clinical trial of new drugs matched by CGP because of their deteriorated physical condition and restriction of the acceptable treatment line . In addition, CGP for patients who had completed the SOC did not achieve an improved prognosis . The National Comprehensive Cancer Network and the European Society for Medical Oncology recommend the use of CGP for selected cancers in daily practice, as well as for research purposes in academic centers.…”

“… 9 , 10 , 11 , 12 In addition, CGP for patients who had completed the SOC did not achieve an improved prognosis. 13 , 14 The National Comprehensive Cancer Network and the European Society for Medical Oncology recommend the use of CGP for selected cancers in daily practice, 5 , 7 as well as for research purposes in academic centers. To our knowledge, the outcomes shown with CGP before first-line cancer treatments have not been reported and more evidence is needed.…”