Selecting Therapy for Poor-Risk Advanced RCC

Earle Burgess, MD:Now that we have multiple options available for frontline treatment with patients with metastatic kidney cancer, none of the current regimens have been directly compared to each other, and so we have to use various clinical factors in trying to select what the optimal regimen for any particular patient is. Typically the considerations that I include are, what is the risk status? We discussed this earlier. There are 2 primary risk scoring systems that are utilized for patients with advanced kidney cancer. The older MSKCC [Memorial Sloan Kettering Cancer Center] system is based on the cytokine era, and the more recent IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] risk criteria based on the TKI [tyrosine kinase inhibitor] era prior to the development of immunotherapy.

We know with the current standard frontline regimens that the efficacy is not consistent across all of the risk groups. For this reason, it’s important that all patients when initially diagnosed with metastatic disease undergo risk classification using one of these systems. Personally, I use the newer IMDC criteria.

Other considerations include what is the burden or sites of disease? How symptomatic is the patient? The regimens we use haven’t been directly compared to each other; however, looking at the response rates across the trials, it appears that there may be differential responses depending on the regimen. For example, if we have a patient who has a higher burden of disease that’s symptomatic and we need a higher likelihood of response, or lack of progression, that may influence the regimen selection.

Other considerations also are the method of delivery. Some patients have a preference for or against oral versus intravenous therapy. There’s a convenience certainly to intravenous therapy only, and having to come to the office every 3 or 4 weeks. Some patients don’t like to be bothered by an additional pill burden, as often patients with advanced kidney cancer have other comorbidities and are taking multiple additional medications. So patient preference in terms of mode of delivery should be considered.

Of course, the adverse effect profiles for the classes that we consider, the VEGF tyrosine kinase inhibitors, have a very different adverse effect profile than the immune checkpoint inhibitors. This is considered in the context of comorbidities and patient fitness. We know that the VEGF tyrosine kinase inhibitors tend to have common gastrointestinal toxicities, hypertension, that need to be accounted for based on the patient’s other conditions.

Specifically, immune-related adverse events [AEs] present differently than what we typically see with the TKIs as well. With monotherapy, immune checkpoint inhibitors have a low adverse event rate. It’s more common with dual therapy, but the presentation often, although less common, is typically more serious than we see with the VEGF tyrosine kinase inhibitors. The AE profiles and the differences also need to be considered when selecting a regimen for patients.

Transcript edited for clarity.

Case: A 68-Year-Old Man With Poor-Risk RCC

A 68-year-old man presented with a 6-week history of painless intermittent hematuria, fatigue and a 7-lb weight loss.

H & P:

• History of medically controlled hypertension and hypercholesterolemia
• 30 pack/year smoking history, social alcohol use  
• Thin, ill-appearing; able to meet activities of daily living but unable to work due to fatigue. He spends more than half the day active on his feet

Labs:

• CBC: Hb 11.4 g/dL, corrected Calcium,11.2 mg/dL, WBC, PLT, LFT all WNL
• BP: 134/92
• Lipid panel: WNL
• U/A: gross hematuria

Imaging:

• CT scan of the chest/abdomen/pelvis showed a left-sided 8.7 (I believe he said 8cm) cm renal mass, para-aortic lymph nodes, and pulmonary metastases

Diagnosis:

• Underwent radical left nephrectomy; found to have Fuhrman grade 4 clear cell carcinoma without sarcomatoid features
• IMDC risk-score: poor

Treatment:

• Initiated treatment with ipilimumab 1mg/kg IV + nivolumab 3mg/kg IV q3w for 4 doses; achieved partial response; received maintenance nivolumab for 6 doses (q4w) followed by disease progression
• Patient was switched to cabozantinib 60mg PO qDay