Evaluating barriers to uptake of comprehensive genomic profiling (CGP) in advanced cancer patients (pts)

Background: Despite increasing evidence of benefit supporting CGP in personalizing cancer therapy, its widespread uptake remains limited. Barriers include low patient understanding, unmet patient expectations related to low utility, clinician concerns over cost-effectiveness, perceived value, and discomfort in management of complex genomic results. Methods: This prospective cross-institutional demonstration study was designed to evaluate implementation of CGP in the care of adult and paediatric advanced cancer pts, incorporating pt reported outcomes (PROMs), discrete choice experiment (DCE), ongoing process optimization and clinician evaluations. DNA sequencing of FFPE tumor and matched blood was completed with CGP (PMCC Comprehensive Cancer Panel; 391 genes) via central laboratory. A tumor board reported results weekly with emphasis on therapeutic relevance. Oncologists performed consent and results delivery. Pts completed pre-and post-test surveys, including validated and study-specific questions, DCE and if eligible, semi-structured interviews. Qualitative interviews were undertaken with study clinicians and laboratory staff to evaluate processes. Results: 86% (315) of 365 enrolled pts had successful CGP; of these 63% (199) had relevant therapeutic, diagnostic or germline results. 50 (16%) had treatment change at 6m, 49 (16%) had germline mutations. 293 (88% of adult pts) completed PROMs. 17 of 19 clinicians/laboratory staff approached consented to an interview. At consent pts cited multifaceted value in testing, showed good understanding of basic concepts, but most (69%) overestimated the likelihood of result-led change. Post-test pts remained consistently satisfied with accessing CGP; valuing research contribution, taking opportunities and information for family. 21% struggled with understanding results but there were low levels of decisional regret following participation (89% had nil/mild regret). Pt-elicited preferences (via DCE) indicated priority for high rates of clinical utility and timeliness. Clinicians sited collaboration and communication as critical to delivery of CGP. Conclusions: Pts undergoing CGP are generally satisfied, and derive value on its use beyond potential therapeutic benefit. Our results suggest that to improve test utility and delivery of CGP with value to pts and investing institution, focus must be placed on addressing the additional barriers to its wider implications including efforts to improve process efficiencies, clinician genomic literacy and decision-making support

iPREDICT: Incorporating complex profiling of patients to enrol onto molecularly directed cancer therapeutics. Preliminary results of the adult and paediatric cohorts

Background: Tumour molecular profiling is an important component of precision oncology. The genomic rearrangements identified in tumours now contribute important information to facilitate accurate diagnosis, prognosis and increasingly can guide therapeutic decisions. iPREDICT (iPR) is a national precision medicine study, offering targeted next generation sequencing (NGS) to adult and paediatric patients with high-risk solid tumours with the aim of identifying actionable variants to guide treatment decisions.Aims: This prospective study was designed to assess patient perception, feasibility and clinical impact of a personalised medicine approach utilising NGS for patients with advanced cancer.Methods: iPREDICT was conducted across seven hospitals utilising NGS (PMCC Comprehensive Cancer Panel; 391 genes). A molecular tumour board was established to evaluate results and treatment recommendations. A detailed evaluation of the testing process, result delivery and patient and trial staff perception was conducted though validated and study-specific surveys, discrete choice experiments and semi-structured interviews.Results: Between April 2017 and September 2018, 315 patients with advanced cancer were enrolled across seven sites and underwent tumour and matched germline NGS. 84% (265) had successful tests. Of patients with successful tests, 208 potentially actionable findings were detected in 144 (55%). 41 (15%) went on to receive a change in treatment; six6 (2%) avoided therapy thought not to be beneficial, nine (3%) received new access to funded therapy, 17 (6%) enrolled on targeted trials and nine (3%) patients commenced off-label therapy. Germline mutations were detected in 46 (17%). A formal evaluation of patient choice and perception of the testing process have provided important insights into health care implementation.Conclusions: Our findings confirm feasibility of molecular profiling in high-risk solid tumours in the Australian health system. The use of NGS provides a practicable approach that yields a clinically significant rate of variant identification and can lead to change of management for patients