CATCH: A Prospective Precision Oncology Trial in Metastatic Breast Cancer

Abstract

PURPOSE CATCH (Comprehensive Assessment of clinical feaTures and biomarkers to identify patients with advanced or metastatic breast Cancer for marker driven trials in Humans) is a prospective precision oncology program that uses genomics and transcriptomics to guide therapeutic decisions in the clinical management of metastatic breast cancer. Herein, we report our single-center experience and results on the basis of the first 200 enrolled patients of an ongoing trial. METHODS From June 2017 to March 2019, 200 patients who had either primary metastatic or progressive disease, with any number of previous treatment lines and at least one metastatic site accessible to biopsy, were enrolled. DNA and RNA from tumor tissue and corresponding blood-derived nontumor DNA were profiled using whole-genome and transcriptome sequencing. Identified actionable alterations were brought into clinical context in a multidisciplinary molecular tumor board (MTB) with the aim of prioritizing personalized treatment recommendations. RESULTS Among the first 200 enrolled patients, 128 (64%) were discussed in the MTB, of which 64 (50%) were subsequently treated according to MTB recommendation. Of 53 evaluable patients, 21 (40%) achieved either stable disease (n = 13, 25%) or partial response (n = 8, 15%). Furthermore, 16 (30%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line. CONCLUSION The initial phase of this study demonstrates that precision oncology on the basis of whole-genome and RNA sequencing is feasible when applied in the clinical management of patients with metastatic breast cancer and provides clinical benefit to a substantial proportion of patients.

Comparing Survival Outcomes for Advanced Cancer Patients Who Received Complex Genomic Profiling Using a Synthetic Control Arm

“…Notably improved evidence for the comparative effectiveness of CGP in terms of improved survival is only an initial step towards translation as subsequent economic evaluations will be largely influenced by therapeutic access and costs. Further research utilising linked clinical and genomic real-world data will be key to identifying cancer populations and timepoints when using CGP to inform treatment will be particularly valuable and encourage large-scale testing access for those most likely to yield real-time survival benefits [12,[36][37][38][39].…”

Precision medicine in the real-world setting. Clinical activity of talazoparib in a woman with hormone receptor-positive HER2-negative metastatic breast cancer with pathogenic mutation in somatic BRCA2

“…Under these circumstances, the role of MTBs is essential. To illustrate this, Hlevnjak et al [14] reported the experience of the first 200 ABC patients that had a DNA or RNA whole-genome or transcriptome sequencing (CATCH study). Of the 128 subjects that were discussed in a MTB and in 64 cases (50%), treatment was indicated considering MTB's recommendations.…”

Targeted Therapy in HR+ HER2− Metastatic Breast Cancer: Current Clinical Trials and Their Implications for CDK4/6 Inhibitor Therapy and beyond Treatment Options

“…We still know far too little about predictive biomarkers for CDK4/6 inhibitors, and therefore the data and analyses only partially explain the differing benefits of MBC patient subgroups. As the relevance of individualized medicine increases, studies considering the complexity of patient-related and tumor-related factors are crucially needed [ 33 , 34 ] ( Table 2 ).…”

“…It is assumed that the complex mechanism of acquired resistance is not yet fully understood. The only predictive biomarker for CDK4/6 inhibitors remains a positive estrogen receptor status; further biomarkers that predict sensitivity for or resistance to CDK4/6 inhibitors are still missing [ 27 , 34 , 51 ].…”