Oncologist. 2020 Nov 29. <br />https://doi.org/10.1002/onco.13617<br /><br />A 48âyearâold man with type 2 diabetes, hypertension, and hypothyroidism presented with lower left chest pain in April 2010. Xâray showed a left anterior chest wall lesion that subsequent computed tomography (CT) scan confirmed was a 4.8âcm lytic lesion with fracture involving the left anterior fourth rib and small bilateral pulmonary nodules. CTâguided biopsy of the rib lesion was consistent with mRCC. He underwent staging scans, which showed a 4.5 × 5.6 left renal mass and posterior left seventh rib bone lesion. He underwent debulking left nephrectomy in May 2010, confirming clear cell renal cell carcinoma. Given his young age and otherwise low disease burden, he was started on highâdose interleukinâ2, which he tolerated without major complications. He had stable disease until 2014, at which time he had increased pulmonary nodules, 1.7âcm right kidney lesion, azygoesophageal lymphadenopathy, and a pancreatic tail mass. From 2014 to 2016, he had disease progression on sunitinib and subsequently with pazopanib, with increasing pulmonary nodules, pancreatic tail lesion, lymph nodes, lytic bone lesions, new liver lesions, and peritoneal carcinomatosis (Fig. 1A). He subsequently started on cabozantinib at 60 mg daily in October 2016, with dose reductions to 40 mg in November 2016 and then 20 mg daily by January 2017 because of fatigue and progression from grade 1 to 2 mucositis. However, he had disease progression by April 2017, with increased mediastinal lymph nodes, a new liver lesion, and an increasing soft tissue lesion next to a right lateral third rib lesion (Fig. 1B). He was switched to nivolumab from April 2017 until September 2017 but developed increased thoracic lymph nodes, increasing pancreatic head lesions, and a right renal mass (Fig. 1C). The decision was made to treat with offâlabel combination cabozantinib 20 mg daily and nivolumab. Treatment began in September 2017 with nivolumab and cabozantinib, with excellent disease control. Treatment was switched to 5 days on cabozantinib 20 mg daily, with 5 days off in October of 2018 because of cheilitis and fatigue and then 7 days on and 7 days off in January 2019. He had stable scans and symptoms for 22 months (Fig. 1D) from initiation of combination therapy until, in July 2019, he had progression of disease in his chest, abdomen, bilateral ribs, and pleura. The patient ultimately transitioned to hospice and died in September 2019.