HPV circulating tumor DNA to monitor the efficacy of anti‐PD‐1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report |
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Authors: | Luc Cabel François‐Clément Bidard Vincent Servois Wulfran Cacheux Pascale Mariani Emanuela Romano Mathieu Minsat Ivan Bieche Fereshteh Farkhondeh Emmanuelle Jeannot Bruno Buecher |
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Institution: | 1. Department of Medical Oncology, Institut Curie, PSL Research University, Paris and Saint Cloud, France;2. Versailles Saint‐Quentin‐en‐Yvelines & Paris‐Saclay University, Saint Cloud, France;3. Department of Radiology, Institut Curie, PSL Research University, Paris and Saint Cloud, France;4. Department of Surgery, Institut Curie, PSL Research University, Paris and Saint Cloud, France;5. Institut Curie, Center of Cancer Immunotherapy, INSERM U932, France;6. Department of Radiotherapy, Institut Curie, PSL Research University, Paris and Saint Cloud, France;7. Department of Genetics, Institut Curie, PSL Research University, Paris and Saint Cloud, France;8. Paris Descartes University, Paris, France;9. Department of Pathology, Institut Curie, PSL Research University, Paris and Saint Cloud, France |
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Abstract: | Squamous cell carcinoma of the anal canal (SCCA) is a rare HPV‐associated cancer with limited sensitivity to standard chemotherapy. In a phase 2 study, nivolumab, an anti PD‐1 immune checkpoint inhibitor, demonstrated significant efficacy as single‐agent therapy in metastatic SCCA patients. Nevertheless, imaging assessment by standard RECIST criteria of the efficacy of immune therapy can be difficult in some patients due to tumor immune cell infiltration, and biomarkers of treatment efficacy are needed. We have previously developed a quantitative droplet digital PCR (ddPCR) technique to detect HPV circulating tumor DNA (HPV ctDNA), with excellent sensitivity and specificity. Here, we report, for the first time, the kinetics of HPV ctDNA during therapy in a patient with metastatic SCCA, who obtained sustained partial response to single‐agent nivolumab. We observed an early and very significant decrease of HPV ctDNA during therapy from the baseline level of 3713 copies/ml plasma to 564 copies/ml plasma at 4 weeks, and 156 copies/ml at 6 weeks, followed by a plateau. This observation provides proof‐of‐concept that HPV ctDNA can be used as a noninvasive early dynamic biomarker to monitor the efficacy of new immunotherapy agents. |
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Keywords: | circulating tumor DNA human papillomavirus anal canal immunotherapy nivolumab |
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