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Case Study of ‘Long-Lasting’ Response to Nivolumab in Patient With BRCA1 Mutation

By: Kayci Reyer
Posted: Tuesday, September 3, 2019

According to a case study published in Clinical Genitourinary Cancer, a patient with metastatic clear cell renal cell carcinoma and a BRCA1 mutation experienced a “long-lasting” partial response to the immune checkpoint inhibitor nivolumab. “We postulate the hypothesis that our metastatic clear cell renal cell carcinoma patient might have well responded with nivolumab treatment because of the presence of a pathogenic germline BRCA1 mutation,” noted Benoit Beuselinck, MD, of the Leuven Cancer Institute in Belgium, and colleagues.

The case study centered on a male patient, aged 69 years, who had undergone a radical nephrectomy with lymphadenectomy to treat grade 4 clear cell renal cell carcinoma. The patient experienced a relapse more than 10 years later with metastases to his liver; the disease progressed until a metastasis developed near the diaphragm 2 years after that.

After first-line sunitinib treatment, the patient achieved a partial response for a duration of 27 months. Second-line axitinib was introduced due to continued disease progression, but the patient developed bone lesions and adenopathy within 3 months. Finally, third-line nivolumab was administered. In addition, the patient underwent radiation for a metastasis on the sternum. An initial evaluation 2 months later revealed stable disease. About 4 months after the start of immunotherapy, all lesions had responded to treatment, as shown on computed tomography imaging. At recent follow-up, the patient showed a “deep” partial response.

The patient was also found to have a germline pathogenic BRCA1 mutation. When compared with the median expression levels of 290 patients with clear cell renal cell carcinoma, the patient’s primary kidney tumor had twice the level of VEGFR2-mRNA, although its expression of P-1 and PD-L1 was below median. Researchers also noted two other case studies of patients with metastatic renal cell carcinoma and somatic or germline mutations who benefited from immunotherapy.

Disclosure: Dr. Beuselinck received an unrestricted research grant and a speaker’s fee from Bristol-Myers Squibb. The other authors reported no conflicts of interest.



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