Abstract P4-07-51: Impact of the Theralink CLIA protein/phosphoprotein assay on treatment selection in routine clinical practice: a prospective observational study in advanced breast cancer
Authors: Weinberg Kris , Pierobon Mariaelena , Blais Edik , Davis Justin , O’Shaughnessy Joyce , Petricoin Emanuel F. 
Published: March 2023

Abstract
Background: The Theralink Reverse Phase Protein Array-based (RPPA) CLIA assay is a novel molecular assay developed to assist physicians in therapy selection for patients diagnosed with advanced/recurrent breast cancer. The assay was specifically designed to quantitatively measure protein activation/phosphorylation of 32 FDA-approved and Phase III drug targets and pathway-linked downstream substrates, providing functional information on actionable oncogenic drivers in individual tumors. Given the recent commercialization of the Theralink assay (TLA), knowledge gaps exist regarding its use in routine clinical practice and the impact of the test on clinical decision-making in real world practice. The primary objective of this analysis was to assess how the TLA has been integrated in therapy selection for breast cancer patients with a focus on understanding its target population, the rationale for patient selection by the treating physician, and the utilization of the molecule information generated by the assay as part of the therapeutic decision-making process. Findings from this study will help optimize patient selection and maximize the clinical impact of the test as a tool for advancing precision oncology. Methods: We prospectively collected data from 124 women with advanced breast cancer whose tumors were profiled using the Breast Cancer TLA from February, 2021 to May, 2022. All patients were confirmed as actively managed for advanced/recurrent breast cancer. Eight μm FFPE sections (n=5) from a recently collected tissue biopsy were used to isolate tumor epithelia via Laser Capture Microdissection and to generate RPPA-based molecular profiles. Clinical management and therapy selection information for 68 patients was gathered via surveys completed by treating physicians. Results: Median age of the 124 participants was 53 years (range 26-82) and 111 (89.5%) patients had stage IV disease. The cohort included 66 hormone receptors positive (of which 5 were HER2+), 51 triple negative, and 7 HR-/HER2+ breast cancers. The TLA yielded molecular information for all specimens and profiles were generated on average in 11 days. One or more targets were highly activated (highly actionable) in 91 patients (73.4%) and moderately activated (partially actionable) in 29 patents; only 4 patients had no actionable target (3.2%). Previous treatment information was available for 118 (95.2%) patients. The TLA was requested to assist with the selection of first-line treatment in 36 patients (of which 24 had previously received neoadjuvant treatment), second-line treatment in 35 patients and third- or subsequential-lines of treatment in 47 patients. Clinicians provided feedback on the use of the assay for 68 patients included in the study. The survey revealed that the TLA impacted treatment selection in 50 (73.5%) cases and was used to either expand options beyond standard of care (30 cases), refine/re-prioritize available treatments (11 cases), narrow treatment from a plethora of options (2 cases) or a combination of the three (7 cases). When TLA data were used for treatment selection, physicians defined the assay highly and moderately beneficial for patient management in 15 and 27 cases, respectively. Conclusion: Our study suggests the TLA yields useful information for selecting treatment for breast cancer patients with advanced/recurrent disease. In this prospective analysis, the assay identified actionable targets in more than 90% of patients, which is significantly higher than what has previously been reported for genomic profiling alone. Overall, physicians found the information yielded by the assay useful for selecting treatment. The inclusion of the TLA in oncology may offer important insights for advancing precision medicine for breast cancer patients.
Citation Format: Kris Weinberg, Mariaelena Pierobon, Edik Blais, Justin Davis, Joyce O’Shaughnessy, Emanuel F. Petricoin. Impact of the Theralink CLIA protein/phosphoprotein assay on treatment selection in routine clinical practice: a prospective observational study in advanced breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-51.