Successful management of retinal metastasis from renal cancer with everolimus in a monophthalmic patient: a case report | Journal of Medical Case Reports

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Retinal metastases are unusual complications of malignancies [1]. Nevertheless, some authors have reported a recent increase in the incidence of metastases in infrequent sites, such as brain or bone, probably due to the expanded treatment options and the resulting improved survival [7, 8].

The most common intraocular tumor is choroidal metastasis from lung cancer in men and breast cancer in women [8]. In the absence of specific series in the literature, the incidence of renal cancer metastasizing to the retina is certainly even lower than to other sites [9]. The prognosis of choroidal metastasis depends on its primary site [9].

The diagnosis is suspected on the basis of the appearance of visual disturbances and the presence of significant eye pain in a patient followed for cancer [8, 9]. It is confirmed by retinal angiography, which shows nodular detachment [8, 9]. Some imaging methods, such as magnetic resonance imaging (MRI) or computed tomography, can individualize a retinal process [8, 9]. Fine-needle aspiration biopsy may be indicated in some situations, such as uveal metastasis without known primary tumor and patients requesting histopathological confirmation before undergoing recommended therapy such as enucleation [10]. Our patient could not benefit from an MRI, owing to the foreign body persisting within the left orbit since his war injury, which had caused the loss of his left eye 30 years ago. He was followed for evolutionary kidney cancer and did not require histological confirmation. Treatment options include observation if the patient is preterminal or the metastasis appears regressed; systemic therapy (immunotherapy, targeted therapy) or whole-eye radiotherapy if the metastases are multifocal, bilateral, or associated with extensive subretinal fluid; plaque radiotherapy for solitary metastasis; and enucleation, which is considered in very limited cases such as choroidal metastasis that is progressive and causes refractory pain [1012].

Until recently, metastatic renal cell carcinoma was considered a cancer with a poor prognosis. Treatment options were limited to cytokines (interferon, interleukin 2). Recent years have been marked by the recognition of several small molecules in metastatic renal cancer [13]. Everolimus (RAD001) is an orally administered inhibitor of the mammalian target of rapamycin, a component of an intracellular signaling pathway that regulates cellular metabolism, growth, proliferation, and angiogenesis [13, 14]. Everolimus has become individualized as a serious option after failure of antiangiogenic therapy [14]. Investigators in the RECORD-1 phase III trial compared everolimus with placebo in patients with metastatic renal cell carcinoma that had progressed while they were receiving sunitinib, sorafenib, or both [14]. Median progression-free survival (PFS) was significantly better in the everolimus arm (4.9 vs. 1.9 months; HR 0.33; P < 0.001), and 21% of patients had previously received one systemic treatment option. Median overall survival (OS) was similar between the two groups (HR 0.90; 95% CI 0.71–1.14). The most common grade 3/4 adverse events in the everolimus arm were asthenia, stomatitis, pneumonitis, dyspnea, infections, fatigue, dehydration, and abdominal pain [14]. Updated analysis showed median OS of 14.8 months in the everolimus arm vs. 14.4 months in the control group (HR 0.87; P = 0.162); however, preplanned crossover occurred in 79.9% of patients and probably confounded the survival benefit. Only 1% of patients in that study achieved a partial objective response [14]. Our patient had a clear partial response estimated to be 50% with a good tolerance of everolimus. Although the benefits of everolimus may need to be evaluated in clinical trials, this may not be feasible, owing to the rarity of the choroidal metastasis of clear cell renal cancer.

Nivolumab is a humanized antibody against programmed cell death protein 1 receptor. Researchers in a pivotal trial (CheckMate 025) enrolled 821 previously treated patients and randomized them to a nivolumab arm (3 mg/kg every 2 weeks) or an everolimus arm (10 mg daily). The primary endpoint of their study was OS. Nivolumab significantly improved median OS (25.0 vs. 19.6 months; HR 0.73; 95% CI 0.60–0.89; P = 0.0018). The overall response rate was better with nivolumab (25% vs. 5%), whereas there were no difference in the median PFS (4.6 vs. 4.4 months) [15].

Cabozantinib is a multikinase inhibitor targeting vascular endothelial growth factor receptor, MET, RET, and AXL. These tyrosine kinases are involved in oncogenesis, metastasis, tumor angiogenesis, and drug resistance. METEOR was a phase III study in which researchers randomized 658 previously treated patients to cabozantinib 60 mg daily or to everolimus 10 mg daily. Median PFS (the primary endpoint of the study) was significantly better with cabozantinib (7.4 vs. 3.8 months; HR 0.58; 95% CI 0.45–0.74; P < 0.0001). The response rate was also better with cabozantinib (21% vs. 5%) [16]. Both nivolumab and cabozantinib are still not available in Morocco.

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