Frontline Treatment Standard in mRCC

Thomas Hutson, DO, PharmD:The frontline treatment strategy employed in this particular patient may not be what many of us would use today. Over the past 15 to 16 months, we have seen the emergence of new therapy which has supplanted sunitinib as a primary therapy in the frontline setting for intermediate- and poor-risk disease.

What I’m specifically talking about is the phase III trial which established ipilimumab, nivolumab as a primary therapy in this same patient population, with a 9% complete response rate, and the data suggest that cabozantinib may also be beneficial in the setting. Please note that the FDA has approved both of these agents as a frontline therapy option, and they have subsequently received NCCN category designation.

So, in my particular practice, I would be leaning more towards using one of those agents in this patient than sunitinib. Because of the approval of new agents in the frontline space, we are likely to see for the first time, a dichotomy in the way the world manages frontline RCC. What do I mean there? I mean that the United States FDA has approved 2 agents that likely will take months to years to be approved around the world, and there could be countries around the world that do not approve these agents.

As we move forward, and we are starting to develop clinical trials, we are going to be in the same position that many other tumor types are where we’re going to have different standard therapies employed in the frontline setting around the world. In the United States, our practice patterns would suggest that there is going to be a change that is emerging with the use of either ipilimumab/nivolumab or cabozantinib as a frontline therapy. And on the heels of this is going to be the result of several immunotherapy TKI trials versus sunitinib that may also show positive, and, therefore, there will be many options potentially in the United States beyond single-agent targeted therapy. The days in which sunitinib or pazopanib are standards in the frontline setting are quickly passing.

Now, one could clearly say looking at the data that there was an absence of data in the good-risk frontline setting. In that setting many patients would potentially receive benefit with single-agent TKI. However, there have been data from a trial combining atezolizumab and bevacizumab, which showed benefit even in good-risk patients over sunitinib. However, this combination has yet to receive FDA regulatory approval.

Transcript edited for clarity.

A 70-Year-Old African-American Woman with Metastatic RCC

December 2017

• A 70-year-old African-American woman presented to her PCP with loss of appetite, fatigue, abdominal pains, and blood in her stool
• CT of the chest, abdomen, & pelvis: distal esophageal thickening and appearance of a solid mass on the inferior pole of the right kidney (3.4 × 2.6 cm); well-defined hypodense nodules in the right lobe of the thyroid (2.1 × 2.8 cm) and bilateral adrenal glands
• Biopsy of renal mass revealed neoplastic cells with clear cytoplasm arranged in nests and mitotic figures suggesting clear cell carcinoma
• FNA from the thyroid nodule revealed neoplastic clear cells on cytology
• IHC; PAX8+, CAIX+, TTF-1(-)
• Diagnosis; right-sided renal cell carcinoma with clear cell histology; thyroid and bilateral adrenal metastasis (T4N0M1)
• She underwent right radical nephrectomy, right adrenalectomy, and radiofrequency ablation of left adrenal metastasis
• She was subsequently started on sunitinib and achieved a partial response within 3 months

June 2018

• Seven months later, the patient reports having increased fatigue
• MRI shows progression in both adrenal lesions
• Therapy was changed to lenvatinib plus everolimus