Delivering precision oncology in metastatic breast cancer: Clinical impact of comprehensive genomic profiling—The CATCH experience

Abstract

CATCH is a prospective precision oncology registry trial that exploits whole-genome/exome- and RNA-sequencing to enable actionable biomarker detection in metastatic breast cancer (mBC) patients of any subtype. We herein report long-term follow-up of the first 558 patients consecutively recruited into CATCH in a monocentric setting between June 2017 and October 2021. Main outcome measures were the rate of implementation of molecular tumor board (MTB) recommended treatments and treatment response as assessed by disease control rate, objective response rate and PFS ratio. Out of the recruited patients, 412 (54.9% HR+/HER2−, 31.3% TNBC, 6.8% HR−/HER2+ and 7.0% HR+/HER2+) were reviewed in the MTB. An appropriate molecularly guided anti-cancer treatment as recommended by MTB was implemented in 183 (44.4%) patients. Gene expression and computationally derived composite biomarkers further expanded treatment options in up to every second patient as compared to genomic sequencing data alone. The outcome was assessed in 152 patients and showed a Disease Control Rate (DCR) of 58.6% and an Objective Response Rate (ORR) of 27.0%. One in three patients (32.8%) showed at least a 50% longer PFS with molecularly guided therapy compared to the previous standard therapy. Notably, 86.4% of the MTB-driven implementations were off-label. CATCH highlights the impact of whole-genome/exome in combination with RNA sequencing to detect clinically relevant biomarkers in mBC. Omics-guided targeted therapy in a real-world setting allows high treatment implementation rates yielding outcome benefit for one-third of the patients.