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Clinical Utility of Genomic Profiling Tests in Patients with Advanced Gastrointestinal Cancers

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Abstract

Background

Comprehensive analyses of cancer-related genomic alterations are expected to lead to increased availability of targeted therapies. However, in patients with gastrointestinal (GI) cancers, the utility of genomic profiling is unclear because of common non-druggable alterations and rapid disease progression that prevent a sufficient time period to seek targets.

Objective

The aim of this study was to determine the utility of genomic profiling tests in patients with GI cancers.

Methods

The subjects of this retrospective study were patients with GI cancers and patients with non-GI cancers who underwent tissue-based genomic profiling at a single institution from April 2017 to October 2020. The profile of gene alterations, frequency of tumor mutational burden-high (≥ 10 Muts/Mb), and accessibility of recommended molecular targeted therapy were compared between patients with GI cancers and patients with non-GI cancers.

Results

In all, 133 patients with GI cancers and 63 patients with non-GI cancers were included. The genomic profiles of GI cancers showed the highest frequencies of TP53, KRAS, and APC mutations and a significantly lower frequency of PIK3CA mutations than those of non-GI cancers. Tumor mutational burden-high was significantly less prevalent in GI cancers (4% vs 20%, p = 0.008). Twenty-nine patients with GI cancers (40%) and 35 patients with non-GI cancers (56%) were recommended for targeted therapies based on the findings. Among them, seven patients each with GI cancers and non-GI cancers received the recommended therapy on their genomic findings, which showed similar treatment accessibility between the GI and non-GI cancer groups (10% vs 11%, p = 0.791). HER2-targeted and BRAF-targeted therapies were the primary treatments administered to patients with GI cancers.

Conclusions

Although their genomic profiles revealed fewer druggable sites, patients with GI cancers accessed targeted therapies similarly to patients with non-GI cancers. The utility of genomic profile testing in patients with GI cancers was highlighted to determine if patients can receive specific treatments, such as HER2-targeted and BRAF-targeted therapies.

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Acknowledgements

The authors thank the investigators of the SCRUM-Japan GI-SCREEN study for their operation and data management. They also thank Enago (www.enago.jp) for the English language review.

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Authors and Affiliations

  1. Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan

    Hiroyuki Takeda, Kumiko Umemoto, Ayako Doi, Hiroyuki Arai, Yoshiki Horie, Takuro Mizukami, Tomoyo Oguri, Takashi Ogura, Naoki Izawa & Yu Sunakawa

  2. Center for Genomic Medicine, St. Marianna University Hospital, Kawasaki, Japan

    Kiyomi Imoto & Yu Sunakawa

  3. Department of Bioinformatics, St. Marianna University Graduate School of Medicine, Kawasaki, Japan

    Hiroyuki Yamamoto

  4. Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan

    Hiroyuki Yamamoto

  5. Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan

    Yoshihisa Yamano

  6. Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan

    Yoshihisa Yamano

Authors
  1. Hiroyuki Takeda
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  2. Kiyomi Imoto
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  3. Kumiko Umemoto
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  4. Ayako Doi
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  5. Hiroyuki Arai
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  6. Yoshiki Horie
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  7. Takuro Mizukami
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  8. Tomoyo Oguri
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  9. Takashi Ogura
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  10. Naoki Izawa
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  11. Hiroyuki Yamamoto
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  12. Yoshihisa Yamano
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  13. Yu Sunakawa
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Corresponding author

Correspondence to Yu Sunakawa.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of Interest/Competing Interests

Takuro Mizukami has received grants from Taiho Pharma, Eli Lilly Japan, and Ono Pharma, and have received honoraria from Taiho Pharma, Chugai Pharma, Bayer Pharma, Merk Serono Pharma, Takeda Pharma, Eli Lilly Japan, Asahi Kasei Pharma Corporation, Otsuka Pharma, Bristol-Myers Squibb, and Ono Pharma. Tomoyo Oguri is an employee of Astra Zeneca K.K. Hiroyuki Takeda, Kiyomi Imoto, Kumiko Umemoto, Ayako Doi, Hiroyuki Arai, Yoshiki Horie, Takashi Ogura, Naoki Izawa, Hiroyuki Yamamoto, Yoshihisa Yamano, and Yu Sunakawa declare that they have no conflicts of interest that might be relevant to the contents of this article.

Ethics Approval

This study was approved by the Ethics Committee of St. Marianna University School of Medicine.

Consent to Participate

All patients provided written informed consent for genomic analysis and use of their data.

Consent for publication

Not applicable.

Availability of Data and Material

Not applicable.

Code availability

Not applicable.

Authors’ Contributions

HT and KI collected the data and performed the analyses. All authors interpreted the data, contributed to the writing and approved the final manuscript.

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Cite this article

Takeda, H., Imoto, K., Umemoto, K. et al. Clinical Utility of Genomic Profiling Tests in Patients with Advanced Gastrointestinal Cancers. Targ Oncol 17, 177–185 (2022). https://doi.org/10.1007/s11523-022-00871-4

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  • DOI: https://doi.org/10.1007/s11523-022-00871-4

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