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Colorectal Cancer With High Tumor Mutational Burden and Mesenchymal-Epithelial Transition (MET) Amplification With
Satoru Nakajima1, Akinori Sasaki1, Risa Okamoto1
1Gastroenterology, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, JPN.
Abstract:
Pembrolizumab, an immune checkpoint inhibitor, has shown efficacy in tumor mutational burden-high (TMB-H) solid tumors and has been approved for the treatment of these diseases. Following immune checkpoint inhibitor administration, rapid tumor progression, known as hyperprogressive disease (HPD), has been observed. This report presents the case of a 60-year-old woman diagnosed with mesenchymal-epithelial transition (MET) amplification and TMB-H colorectal cancer. The patient was initially administered chemotherapy for MET amplification in a clinical trial but was considered refractory following one treatment cycle. Subsequently, she was treated with pembrolizumab for the TMB-H solid tumor. However, she developed HPD one month after starting pembrolizumab treatment and later died in the hospital. To the best of our knowledge, this is the first report of HPD in a patient with colorectal cancer harboring both MET amplification and TMB-H. It suggests that MET amplification may be involved in HPD development. These findings underscore the need for vigilance regarding HPD risk when selecting immune checkpoint inhibitor candidates and highlight the importance of future research, such as exploring MET-targeted combination strategies, in the optimization of treatment outcomes.
Insights
Hyperprogressive disease (HPD) is a rare risk following immune checkpoint inhibitor therapy. This case report details HPD in a patient with MET-amplified, high tumor mutational burden colorectal cancer, suggesting MET amplification may contribute to HPD.
Area of Science:
- Oncology
- Cancer Research
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICIs) like pembrolizumab are effective for tumor mutational burden-high (TMB-H) cancers.
- Hyperprogressive disease (HPD) is a rare but severe adverse event following ICI treatment.
- Mesenchymal-epithelial transition (MET) amplification is an oncogenic driver in some solid tumors.
Observation:
- A 60-year-old woman with MET-amplified, TMB-H colorectal cancer developed HPD after one cycle of chemotherapy and subsequent pembrolizumab treatment.
- The patient experienced rapid tumor progression within one month of initiating pembrolizumab.
- This represents the first documented case of HPD in colorectal cancer with both MET amplification and TMB-H.
Findings:
- MET amplification may play a role in the development of HPD in patients treated with ICIs.
- The combination of MET amplification and TMB-H in colorectal cancer presents a unique challenge for ICI therapy.
- Early identification of HPD risk factors is crucial for patient management.
Implications:
- Clinicians should maintain vigilance for HPD in patients receiving ICIs, particularly those with specific molecular alterations like MET amplification.
- Further research is warranted to elucidate the mechanisms linking MET amplification and HPD.
- Investigating MET-targeted combination therapies alongside ICIs may improve treatment outcomes for selected cancer patients.
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