Case study: Complete response to nivolumab after TKI failure in metastatic renal cell carcinoma

The immune checkpoint inhibitor nivolumab induced a complete response (CR) in a patient with metastatic renal cell carcinoma (RCC) who had already received treatment with a multi-targeted tyrosine kinase inhibitor. The case was published in Anti-Cancer Drugs.

Few cases of a CR to nivolumab in the metastatic pretreated setting have been reported in the literature. The case was also notable in that the patient had a favorable risk category. The clinical activity of immunotherapy seems to be superior in previously untreated patients with metastatic intermediate/poor risk RCC, wrote the authors, led by Veronica Mollica and Vincenzo Di Nunno, Azienda Ospedaliero-Universitaria, Bologna, Italy.

“Our patient showed a favorable risk category, suggesting that immune-checkpoint inhibitors could also be strongly active in this subgroup of patients,” they added.

Indeed, such was the case in the Checkmate 214 study, in which combined immunotherapy with nivolumab and ipilimumab was associated with a superior objective response rate and a longer progression-free survival compared with sunitinib in patients with previous untreated advanced RCC with intermediate and poor risk.

On this basis, in April 2018, the US Food and Drug Administration (FDA) approved first-line nivolumab plus ipilimumab for the treatment of patients with intermediate- or poor-risk advanced RCC. Previously, the FDA approved nivolumab for the treatment of patients with metastatic RCC following prior anti-angiogenic therapy, based on an improvement in overall survival compared with everolimus observed in the CheckMate 025 trial. However, in CheckMate 025, only 4 of 410 patients achieved a CR, the authors explained.

Clinical responses after failure of vascular endothelial growth factor receptor inhibitors in this setting are “very rare,” so the main goal has been achievement of stable disease.

In this case report, the authors describe a 44-year-old man who underwent total left nephrectomy for a renal mass; histologic examination showed a clear cell RCC infiltrating the perirenal adipose tissue and the pelvis. The patient had favorable risk according to International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. After failure of experimental treatment with pazopanib, he was treated with sunitinib and achieved stable disease.

More than 3 years later, CT scan revealed progressive disease with an increase in the size and number of pulmonary lesions in addition to the appearance of bone lesions. He was then started on second-line therapy with nivolumab 3 mg/kg. After six cycles of nivolumab, the patient achieved a CR in all previous sites of disease localization.

Other investigators have documented CRs with nivolumab treatment in a patient with a nonclear cell etiology, the authors noted.

“As there are very few cases of a CR to nivolumab in this setting reported in the literature, this case appears to be of particular interest,” they wrote.

They added: “The clinical features of our patient (long-term stable disease with standard antiangiogenesis treatment and its favorable risk category) make us reflect on the role of immunotherapy in this particular subgroup of patients and suggest that immunotherapy could be a useful option also in patients with a favorable IMDC risk score. This issue highlights the need for predictive clinical, molecular, or biological markers of response to immune-checkpoint inhibitors.”

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