Page 14 - Delaware Medical Journal - January 2017
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Successful Therapy with Nivolumab in Metastatic Renal Cell Carcinoma After Multiple Prior Treatments
Nicole C. Finelli, DO; Sarim A. Baig, MD; Gregory A. Masters, MD
Renal cell carcinoma (RCC) is responsible for 80 to 85 percent of all primary renal malignancies. In the United States, there are about 63,000 new cases and almost 14,000 deaths per year from RCC. Surgical resection of localized RCC can be curative but many patients eventually recur. Immunotherapy appears to be a promising new modality for many malignancies, including RCC. Nivolumab, a specific immunotherapy agent indicated for advanced RCC, may restore antitumor immunity and allow for greater progression-free survival by targeting proteins that negatively regulate T cell immunity. This case study aims to demonstrate the integration of nivolumab into the management of a patient with advanced RCC and provide a stimulus for further investigation and research into this treatment modality.
Key words: immunotherapy, renal cell carcinoma, PD1-inhibitor, nivolumab
IntroductionRenal cell carcinomas (RCCs) are responsible for
80 to 85 percent of all primary renal cancers. In the United States, there are about 63,000 new cases and almost 14,000 deaths per doubled over the last 50 years likely owing to earlier detection of tumors, often incidentally found on scans done for other reasons, at smaller sizes and curative surgical treatment. Surgical resection of localized RCC can be curative but many patients eventually recur.
since the late 19th century. More recently, advances in the understanding of immune surveillance of tumor growth have led to the development of novel anti-neoplastic agents. These agents can support the natural ability of the immune system to recognize function by blocking negative regulators of T cell immunity. These include monoclonal antibodies that antagonize the programmed cell death 1 (PD-1) protein, a T cell surface receptor
Nivolumab, a fully human IgG4 PD-1 immune-checkpoint- inhibitor antibody, disrupts PD-1 mediated signaling and may restore anti-tumor immunity, allowing for persistent activation
of the immune system against malignant cells. PD-1 inhibitors such as nivolumab have become an integral part of advanced melanoma and non-small cell lung cancer (NSCLC) management.
Their use is now being extended to other malignances, including advanced RCC. In the phase III CheckMate 025 trial, nivolumab was compared to everolimus in patients with advanced clear
cell renal cell carcinoma. The trial was stopped early based on improved overall survival in patients treated with nivolumab. The following case illustrates a marked clinical and radiological response in a heavily pre-treated patient with advanced RCC having received six prior treatments before nivolumab.
CASE REPORT
for hypertension, hyperlipidemia, tobacco abuse, and multiple inguinal hernia repairs presented in February 2009 to her primary care physician with left-sided groin pain. An abdominal CT scan with intravenous (IV) contrast revealed an enhancing mass in
the right kidney measuring 4.8 x 3.5 cm, concerning for possible malignancy. Subsequent radical right nephrectomy revealed a Stage I (pT1N0M0) clear cell carcinoma.
The patient was followed over the next three years with serial imaging. In May 2012, bibasilar pulmonary nodules were noted on CT scan. CT-guided FNA of a nodule revealed malignant cells consistent with metastatic clear cell carcinoma. Therapy was initiated with the tyrosine kinase inhibitor (TKI), sunitinib. The patient received treatment for six months; however, repeat
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Del Med J | January 2017 | Vol. 89 | No. 1
Abstract
