Robert Alter, MD: I’m going to go to the third case, and we’ll get a little more detailed about it. Maybe we’ll use a different regimen that we haven’t seen before. I had a 56-year-old gentleman. In his medical history you see hypertension, hyperlipidemia, and gastritis. Past surgeries included cholecystectomy, right knee replacement, and cataracts. Medications at home [were Percocet, Norvasc, Lipitor, and senna]. This person was social and had 2 children. He had a 30 pack-year history of smoking, and stopped smoking 6 months earlier. He was a plumber with exposures to the fumes and toxins that a plumber is exposed to. He denied alcohol use and had a family history significant for a paternal grandfather who had gastric cancer.

He presented in March 2021. He had a 2-month complaint of right side back and hip pain. He was limping when he presented. Initially, he went to his chiropractor, who did manipulations for 2 weeks. The chiropractor was unsuccessful, but he swore by his chiropractor. [He went to] the ED [emergency department], and you see his laboratory parameters there. He was a little anemic. His white blood cell count was a little up. His platelets were fine. He was hypercalcemic, so we were given a sense that he was defining his risk categorization.

He had a CT [computed tomography] scan that revealed a 12-by-9.8-by-12-cm mass that pretty much encompassed his entire left kidney and extended locally to the posterior abdominal wall with infiltration and fluid in the posterior perinephric space. He had a 10-by-6.5-cm right iliac bone lesion, which explained the limp, and extraosseous extension into the gluteus musculature. A chest x-ray revealed bilobar pulmonary masses measuring just under an inch. An MRI [magnetic resonance imaging] of the abdomen confirmed the renal mass, 13.4 cm, endophytically extending into the left renal sinus collecting system. As a staging workup in an asymptomatic patient, we did an MRI of the brain and saw several lesions there. There was nominal edema but localized metastases.

Completing the bone workup, his bone scan showed lytic destruction in the right iliac bones. It was surprising that that was his only lesion. That was the area where we biopsied the right iliac bone, which was positive for clear cell renal cell carcinoma. You see the IHC [immunohistochemistry] stains there [positive for EMA, PAX-8, vimentin, CAM5.2]. Then we started to focus on symptom management first. He wasn’t having hematuria. We were cognizant of his symptoms of bone pain. He had asymptomatic brain metastases, so we put out the fire a little first. We made his symptomatic limp become asymptomatic. He went to rehabilitation afterward and did extraordinarily well. He received SBRT [stereotactic body radiation therapy] for his lesions. We put him on Zometa monthly a year ago. We felt that we were taking care of the periphery of his disease, but we had to take care of his central core.

We decided to give him cabozantinib-nivolumab. At this juncture last year, lenvatinib wasn’t FDA approved, though we did have some experience using lenvatinib as a combination therapy in the first line. It still wasn’t FDA approved at that point. We did have data looking at single-agent nivolumab for brain metastases. We had data on cabozantinib for brain metastases. We waited the appropriate time between the initiation of cabozantinib after completion of SBRT. We waited maybe 6 weeks before we started cabozantinib after he finished SBRT. I’m not going to go into detail, but you see the left renal mass initially had shrinkage. It was up to 13 cm, and after 2 months of therapy, it went down to 9.6 cm. Two months later, it went down to 7.9 cm, and he had decrease in the size of the pulmonary lesions.

Now it was November. He’d been on therapy for 7 months. His renal lesion appeared to be stagnant. It was present but not growing. His pulmonary lesions still appeared to be decreasing mildly. His functional performance status had improved significantly. He was very independent and driving himself. Previously, he was coming in a wheelchair. The question we had to address is: Are we tapped out with therapy? Are we doing the best that we can, or should we try a little more?

Rather than adding more drugs, we decided to do a cytoreductive nephrectomy. We took out the renal lesion, which measured 7.5 cm and was grade 2. We don’t have a renal biopsy from before. I can’t tell you if we downgraded the disease. We definitely shrunk the disease. It’s clear cell renal cell carcinoma with extensive necrosis. It still reinvaded the renal sinus and abutted the peritoneal fat. The margins were negative. There was no vascular invasion, and we didn’t suspect any on his initial presentation. He’s had an unremarkable postoperative course.

He still has his pulmonary lesions. His bone lesions seem to be inactive. He had a bone scan that showed no new lesions and faint activity on previous lesions. His right iliac bone isn’t active anymore. We changed his nivolumab to every 4 weeks compared with every 2 weeks, the initial dosage. He still has some toxicity from cabozantinib. We haven’t required dose reductions. We keep him at 40 mg/m2. We’re utilizing urea cream for his grade 1 hand-foot syndrome. He was in the office 2 weeks ago. He’s about to propose to his girlfriend, so hopefully she’s not hearing this.

Transcript edited for clarity.