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Biomarker Testing Journey Among Patients with Advanced Solid Tumors and Treatment Patterns by Homologous Recombination Repair Status: A Clinico-Genomic Database Study

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Abstract

Introduction

Defects in the homologous recombination repair (HRR) pathway can include mutations in BRCA1 and BRCA2 (BRCAm) and other HRR genes (HRRm). These mutations are associated with a homologous recombination deficiency (HRD) phenotype. We evaluated testing journey and treatment patterns by BRCAm, HRRm, and HRD status in a real-world dataset.

Methods

Deidentified data for patients who had undergone comprehensive genomic profiling using FoundationOne®CDx were collected through December 31, 2020, from a real-world multi-tumor clinico-genomic database (CGDB) capturing data from clinics in the United States. Patients eligible for inclusion in this analysis had a confirmed diagnosis with advanced or metastatic disease between January 1, 2018, and December 31, 2019, for 1 of 15 solid tumor types. Objectives were to evaluate patient treatment patterns by BRCAm, HRRm, and HRD status and to describe the timing of when (throughout disease course) comprehensive genomic profiling was performed.

Results

Among 9457 patients included in the overall population with evaluable biomarker status, 7856 (83.1%) received ≥ 1 systemic therapy. Among the 7856 patients who received systemic therapy, 2324 (30.0%) underwent testing before first-line therapy, 4114 (52.4%) were tested after receiving first-line therapy and before receiving subsequent therapy (if any), 970 (12.3%) were tested after second-line therapy and before receiving subsequent therapy (if any), and 447 (5.7%) patients underwent testing after receiving third-line therapy. A higher proportion of patients with BRCAm, HRRm, or HRD-positive status were treated with poly(ADP-ribose) polymerase (PARP) inhibitors across all lines of therapy. There was no evidence of a meaningful difference in the proportion of patients who received other treatment (including chemotherapy and immunotherapy) by BRCAm, HRRm, or HRD status.

Conclusion

The majority of patients from this real-world dataset underwent FoundationOne®CDx testing after initiation of first-line treatment. Testing appeared to influence treatment patterns, with a higher proportion of patients with BRCAm, HRRm, and HRD-positive disease receiving PARP inhibitors.

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Data Availability

The data that support the findings of this study originated by Flatiron Health, Inc. and Foundation Medicine, Inc. These de-identified data may be made available upon request, and are subject to a license agreement with Flatiron Health and Foundation Medicine; interested researchers should contact < cgdb-fmi@flatiron.com > and < dataaccess@flatiron.com > to determine licensing terms.

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Medical Writing And Editorial Assistance.

Medical writing assistance was provided by Ali Hassan, PhD, of ICON plc (Blue Bell, PA, USA). This assistance was funded by MSD.

Funding

Funding for this research and publication, including the journal’s Rapid Service Fee, were provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

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Authors and Affiliations

  1. Merck & Co., Inc., Rahway, NJ, USA

    Changxia Shao, Yixin Ren, Heng Zhou, Liam C. Lee, Cai Chen, Elisha J. Dettman, Razvan Cristescu, Alexander Gozman, Fan Jin & Wei Zhou

  2. Mailstop WP37A-250, 770 Sumneytown Pike, West Point, PA, 19486, USA

    Changxia Shao

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  1. Changxia Shao
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Contributions

Changxia Shao: study concept, design, or planning of the study; acquisition of the data; interpretation of the results; critically reviewing the manuscript. Yixin Ren: planning of the study; analysis of the data; interpretation of the results; critically reviewing the manuscript. Heng Zhou: planning of the study; analysis of the data; interpretation of the results; critically reviewing the manuscript. Liam C. Lee: study concept, design, or planning of the study; acquisition of the data; interpretation of the results; critically reviewing the manuscript. Cai Chen: planning of the study; analysis of the data; interpretation of the results; critically reviewing the manuscript. Elisha J. Dettman: study concept, design, or planning of the study; acquisition of the data; interpretation of the results; critically reviewing the manuscript. Razvan Cristescu: planning of the study; analysis of the data; interpretation of the results; critically reviewing the manuscript. Alexander Gozman: study concept, design, or planning of the study; acquisition of the data; interpretation of the results; critically reviewing the manuscript. Fan Jin: study concept, design, or planning of the study; acquisition of the data; interpretation of the results; critically reviewing the manuscript. Wei Zhou: study concept, design, or planning of the study; acquisition of the data; interpretation of the results; critically reviewing the manuscript.

Corresponding author

Correspondence to Changxia Shao.

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Conflict of Interest

Changxia Shao, Yixin Ren, Heng Zhou, Cai Chen, Elisha J. Dettman, Razvan Cristescu, Alexander Gozman, and Fan Jin are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and own stock in Merck & Co., Inc., Rahway, NJ, USA. Wei Zhou and Liam C. Lee are former employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Wei Zhou is currently an employee of Eli Lilly and Company, Indianapolis, IN, USA. Liam C. Lee is currently an employee of AstraZeneca Pharmaceuticals, One MedImmune Way, Gaithersburg, MD, USA.

Ethical Approval

The IRB approval for the Flatiron Health CGDB was obtained by Flatiron Health prior to the present study. The IRB of WCG IRB (Princeton, NJ, USA) gave ethical approval for the study protocol based on the Flatiron Health CGDB, and included a waiver of informed consent (approval ID 420180044).

Additional information

Liam C. Lee and Wei Zhou were affiliated with Merck & Co., Inc. at time of study.

Supplementary Information

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Shao, C., Ren, Y., Zhou, H. et al. Biomarker Testing Journey Among Patients with Advanced Solid Tumors and Treatment Patterns by Homologous Recombination Repair Status: A Clinico-Genomic Database Study. Adv Ther 41, 759–776 (2024). https://doi.org/10.1007/s12325-023-02734-4

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