Abstract C050: Comprehensive analysis of causes for unsuccessful genomic profiling in a Phase 1 setting

Abstract Purpose: Genomic profiling (GP) has revolutionized personalized cancer therapy, enabling tailored treatment strategies based on individual tumor characteristics. However, despite its widespread use, there are instances where GP fails. Understanding the causes of such failures is important for improving the success rate of GP. Here, we present a comprehensive analysis of unsuccessful GP within a phase 1 clinical setting. Materials and Methods: A prospective, single-center, single-arm open label study (NCT02290522) was conducted, enrolling patients with advanced cancer referred to a phase I unit. Fresh tumor tissue was obtained by core needle biopsy for whole genome- or whole exome sequencing and RNA sequencing. In cases where fresh tumor tissue was unavailable, archival, formalin-fixed, paraffin-embedded tumor tissue or circulating tumor DNA extracted from plasma were obtained. Results: Between March 2013 and December 2021, a total of 2151 patients with advanced cancers and exhausted or almost exhausted treatments options were enrolled in the study. GP was unsuccessful in 281 patients (13%). The reasons for failure were; abstaining from biopsy due to performance decline from the time of consent (115/281= 41%), inadequate tissue quality due to normal tissue or necrosis (52/281= 19%), absence of lesions for tissue biopsy at the time of biopsy (41/281= 15%), patient withdrawal of consent (23/281= 8%), pre-analytical factors preventing tissue or liquid biopsy analysis (14/281= 5%), unsuccessful analyses (13/281= 4%), other treatment initiated at time of planned biopsy (10/281= 4%), unknown reasons (9/281= 3%) or biopsy contraindicated (4/281= 1%). Conclusion: The main cause of unsuccessful GP in this study was pre-analytical factors, primarily linked to performance status decline. Performing the biopsy and GP in earlier treatment lines, may reduce failure rates. Furthermore, considering the risk of rapid performance status decline, prior to biopsy referral, along with reduced lag time from obtaining consent to biopsy, may enhance GP success rates. Citation Format: Cecilie Iden, Laila Belcaid, Ida Jacobsen, Martin Hoejgaard, Iben Spanggaard, Morten Mau-Soerensen, Ulrik Lassen, Christina Westmose Yde, Kristoffer Staal Rohrberg. Comprehensive analysis of causes for unsuccessful genomic profiling in a Phase 1 setting [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C050.