| Summary: | Introduction A case of multiple liver metastases of clear cell RCC with a significant response to sunitinib as the fifth line after nivolumab is reported. Case presentation The patient was a 65‐year‐old man who underwent open nephrectomy for RCC. After the nephrectomy, he had recurrences several times, and metastasectomy had been performed for each recurrence. At 13 years after the nephrectomy, multiple liver, and lung metastases appeared. The treatment was switched to axitinib, followed by cabozantinib, then nivolumab. The best response was PR, SD, and PD for these three drugs, and treatment duration was 14, 3, and 3 months, respectively. As the fifth line, sunitinib was administered, with significant shrinkage of the multiple liver metastases, and PR has been maintained for 34 months. Conclusion Sunitinib after an IO‐drug showed a significant effect in spite of only slight efficacy with other VEGFR‐TKIs, which may have occurred through the alteration of the immunological microenvironment.
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