Durable disease control with cabozantinib in metastatic chromophobe renal cell carcinoma: A rare case with promising outcomes

Abstract

Chromophobe renal cell carcinoma (chRCC) is a rare RCC subtype with limited treatment data. Cabozantinib, a multikinase inhibitor, is effective in clear cell RCC but lacks robust evidence in chRCC.

A 26-year-old male with metastatic chRCC achieved prolonged disease control on cabozantinib despite treatment interruptions. After first-line pazopanib failure, cabozantinib was initiated in January 2023, maintaining stable disease for over two years with only grade I toxicities.

Cabozantinib appears effective in metastatic chRCC, offering prolonged stability with manageable toxicity. Further research is needed to establish its role in this rare RCC subtype.

1 Introduction

Chromophobe renal cell carcinoma (chRCC) is a rare subtype of renal cell carcinoma (RCC), accounting for approximately 5–7 % of all RCC cases. While most major clinical trials in RCC have predominantly focused on clear cell carcinoma (ccRCC) , ^, there is a significant lack of data regarding treatment efficacy in the non-clear-cell subtypes, particularly chRCC. This knowledge gap has hindered the understanding of therapeutic outcomes in this rare subtype. Cabozantinib, an oral multikinase inhibitor, has demonstrated significant therapeutic responses in metastatic ccRCC in phase III trials. However, randomized prospective data are lacking for chRCC. In this report, we present the case of a patient with metastatic chRCC who achieved durable disease control with cabozantinib.

2 Case presentation

A 26-year-old male with a medical history of epilepsy and no familial history of cancer, presented in May 2020 with a 5-month history of low back pain, without hematuria or other urinary symptoms. Physical examination revealed no abnormalities. Computed tomography (CT) imaging showed multiple bilateral renal masses, each measuring less than 2 cm, along with bilateral pulmonary nodules and micronodules suggestive of metastatic disease ( Figs. 1–3 )

Further evaluation with abdominal magnetic resonance imaging (MRI) revealed three cortical nodules in the right kidney measuring 13 mm, 15 mm and 12 mm, and three cortical nodules in the left kidney measuring 18 mm, 14 mm, and 17 mm. Laboratory results were within normal limits.

Pathological assessment of one renal nodule obtained via CT-guided biopsy revealed a carcinomatous proliferation composed of well-defined cells with eosinophilic cytoplasm and hyperchromatic nuclei surrounded by a clear halo ( Fig. 4 ). The tumor cells exhibit intense and diffuse expression of CK7 in immunohistochemistry. ( Fig. 5 ). Based on these findings, a diagnosis of chRCC was established.

The patient had an intermediate IMDC prognostic score. The case was discussed in a multidisciplinary tumor board meeting which included thoracic surgeons. As the pulmonary metastases were not amenable to local treatment, first-line Pazopanib was proposed. Patient was addressed to genetic counseling to rule-out hereditary genetic syndromes.

In August 2020, the patient initiated first-line pazopanib, and the first radiological tumor assessment showed stable disease. However, progressive pulmonary disease occurred in November 2022. Consequently, second-line cabozantinib at a dose of 60 mg per day was started in January 2023. Laboratory tests were conducted every 2 weeks to monitor for potential toxicities. After 4 weeks of therapy, the patient reported only grade I fatigue and grade I hypertension, which required the initiation of antihypertensive drugs. An initial CT scan assessment, performed six weeks after starting cabozantinib, demonstrated stable disease. The patient continued on cabozantinib without major clinical or laboratory toxicities. Follow-up CT scans confirmed stable disease across multiples assessments. Notably, our patient experienced treatment interruption for several months (total interruption time 6 months) due to drug unavailability and delays in treatment approval by health authorities. Despite these periods of discontinuation, the disease remained stable on all subsequent CT scans ( Fig. 2 ). As of January 2025, the patient remains on cabozantinib therapy, with no signs of clinical or radiological progression after 2 years of treatment, and no concerning drug-related toxicities.