Factors Considered When Choosing RCC Treatment Options

The first thing as a patient presents with metastatic renal cell carcinoma, is if a patient is eligible for immunotherapy, I think immune combination is the most important. A patient who is ineligible for immune therapy, often due to a history of poorly controlled autoimmune diseases, that is when we think about TKI [tyrosine kinase inhibitor] monotherapy. In that situation, I think the TKI monotherapies that are recommended by NCCN [National Comprehensive Cancer Network] guidelines are going to sunitinib, pazopanib, and in the case of intermediate- or poor-risk disease, cabozantinib. Given the CABOSUN data showing an improvement in response and PFS [progression-free survival] with cabozantinib over sunitinib, I think that I would prefer cabozantinib in these patients, especially when you look at the toxicity data from CABOSUN, that it overall has relatively comparable tolerability to sunitinib.

At the end of the day, the NCCN guidelines are to help guide therapy. And I think I would agree with those with intermediate- or poor-risk disease, given CABOSUN data, TKI monotherapy, I think cabozantinib would be the preferred approach in that situation.

Is there anyone who is unable to receive immunotherapy? It’s an evolving field. There are data that suggest that even in the presence of autoimmune diseases, you can give patients immunotherapy. And there are also data that show looking at those patients who are on steroids at the start of immunotherapy, there’s concern that patients on steroids actually have a lesser response to immunotherapy. But when they went back and looked at some retrospective datasets, if patients were on steroids for an autoimmune phenomenon, not for disease-related complications, they actually still seem to respond to immunotherapy.

So I think overall, this idea of who can be unable to receive immunotherapy is sort of evolving. In my practice, if I have a patient who has an active autoimmune disease, I’m reluctant to do so. If I have a patient who has a history of ulcerative colitis that had not required management for 10 years, I would certainly consider challenging immunotherapy, or mild RA [rheumatoid arthritis]. But I’ve had patients come into my office who have severe RA with classic joint deformities that are having an impact on quality of life. And in those situations, I certainly do worry that by adding on immunotherapy, I’m going to exacerbate that further and have significant impact on the quality of life.

So it really does come down to a balanced discussion with the patients. I think in renal cell carcinoma we’re fortunate that in patients who may have relative contraindications to immunotherapy, we have great alternatives in cabozantinib or the other VEGF targeted therapies.

Transcript edited for clarity.

Case: A 70-Year-Old Man with Intermediate-Risk RCC

A 70-year-old Caucasian man presented to ER complaining of blood in his urine and abdominal pain.

H & P

• History of ulcerative colitis, controlled hypertension, and controlled hypercholesterolemia
• Lower back tender to touch

Labs

• CBC: Hgb 12.5 g/dL, HCT, PLT, WBC all WNL
• BP: WNL
• Lipid panel: WNL

Imaging

• Bone CT scan of the chest, abdomen, and pelvis showed a bilateral renal mass, a small lytic lesion in the lumbar vertebrae, several pulmonary nodules, and mediastinal and right hilar lymphadenopathy.
• Diagnosis: stage IV clear-cell renal cell carcinoma; intermediate-risk

Treatment

• Received cytoreductive nephrectomy
• He was started on cabozantinib 60 mg daily

Follow-up

• At 3 weeks of therapy patient tolerated treatment well, with mild fatigue and diarrhea, HTN remains controlled; blood in urine and lower back pain resolved; ECOG 0
• At 6 weeks of therapy the patient shows PR and reduction in size of the renal masses and lymphadenopathy.