SOMATIC TUMOUR GENOMIC EVALUATION IN EARLY PHASE CANCER CLINICAL TRIAL PRE-SCREENING

Tumour genomic testing is increasing in routine clinical practice and clinical trial screening/pre-screening. Genetic variants identified may suggest sensitivity/resistance to established treatments or aid patient selection for clinical trials. However, there are still barriers limiting widespread utility. To review recent somatic tumour genomic testing outcomes of cancer patients referred for recruitment consideration to early phase clinical trials at Cambridge, UK. We performed a retrospective database evaluation of Foundation Medicine Testing results between 21/06/2018 and 10/02/2020, including patient demographics and clinical data. 392 patients were tested. 36% were male and the mean ages were 61.1 and 58.2 for female. Primary tumour sites accounting for above 5% of genomic tests were breast 24% colorectal 17%, ovarian 14%, brain 7%, and pancreatic 6%. Prior treatments included cytotoxic 84%, endocrine 23%, immuno 18% or molecularly targeted 14% therapy. 265 patients (68%) were profiled from the 392 referred to the research unit. From the 127 patients not profiled, the three most common reasons were poor performance status 24%, patients opting for standard of care treatment 20% or patients being entered into clinical trials without genomic profiling 19%. A statistically significant age difference was found in the profiled versus not profiled populations for female (56.5 vs 61.7; p<0.05) and overall (57.7 vs 62.2; p<0.05) groups. Profiling was performed for at least half of the total number of patients referred from each tumour group, including all patients with brain tumours (n=26), potentially reflecting the aim to overcome limitations of current standard treatment. The 10 most common altered genes were TP53 55%, APC 26%, PIK3CA 19%, KRAS 18%, CDKN2A 10%, PTEN 10%, TERT 19%, ERBB2 7%, CDKN2B 7%, EGFR 6%. Considering all profiled patients, after genomic testing 208 patients had no management change as a result 78%, 9% were referred for clinical trials in other centres, and 7.5% were eligible for a local early phase trial. Of patients referred to consider early phase trials in our unit, around one in six patients entered a trial informed by genomic profiling. As testing becomes more widespread, it is important that these patients are identified and offered matched trials, and trial portfolios should be managed based on variant prevalence to increase the proportion of patients successfully enrolled in clinical trials