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

TL;DR

The CATCH trial shows that combining whole-genome/exome and RNA sequencing improves treatment outcomes for metastatic breast cancer patients by identifying actionable biomarkers.

Contribution

CATCH demonstrates the clinical benefit of integrated genomic and RNA profiling in real-world metastatic breast cancer treatment.

Findings

44.4% of patients received molecularly guided treatments recommended by the molecular tumor board.

Integrated profiling expanded treatment options for up to half of the patients compared to genomic data alone.

One-third of patients experienced at least a 50% longer progression-free survival with molecularly guided therapy.

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.

What's new?

CATCH is a prospective precision oncology registry trial that harnesses whole‐genome/exome‐ and RNA‐sequencing to enable actionable biomarker detection in metastatic breast cancer patients of any subtype. The data of the first 412 consecutive patients with completed follow‐up in this real‐world, single‐center patient cohort provide robust evidence that comprehensive molecular profiling substantially improves treatment response and progression‐free survival. The integrated profiling approach broadened treatment recommendations beyond those from conventional single‐gene mutation scoring. The reported performance of the CATCH platform underscores the feasibility and clinical benefit of tailoring diagnostic and therapeutic strategies in metastatic breast cancer through precision oncology.

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