Treatment of Refractory Metastatic Renal Cell Carcinoma - Episode 6

Evolving Treatment Paradigms in mRCC

Thomas Hutson, DO, PharmD:At the end of the day we must recognize that we are in a period of time where the paradigm is rapidly changing, not only in the frontline setting, but also for refractory treatment of metastatic RCC. Important things for treating physicians to remember is that in the frontline setting, the goal is obviously to try to get the greatest response possible, and having agents such as ipilimumab and nivolumab combination, with a 9% complete response rate, is very attractive.

Cabozantinib also demonstrates significant level of benefit and exceeds what we had seen with sunitinib. The paradigm has shifted from using oral TKI therapy in the frontline setting as the standard frontline option for all patients.

In the second-line and beyond setting, what’s most important is for the treating physician to become comfortable with 3 agents—nivolumab, lenvatinib/everolimus combination, and cabozantinib. Each of these 3 agents needs to be used early in the refractory setting—second-, third-, or fourth-line. Until there are head-to-head randomized trials comparing these 3 agents, it is going to be an individual physician’s choice based upon their experience as to what sequence these agents should be used in their practice. But at the end of the day, patients should receive all of those 3 therapies.

If you will, in a setting when we’re looking at the choices of therapy in the United States in the frontline setting, it should be considered more often than not to use either nivolumab/ipilimumab, or cabozantinib in intermediate/poor-risk frontline. In the good-risk patients, one could consider using sunitinib or pazopanib. In the second-, third-, and fourth-line, one should employ nivolumab, lenvatinib/everolimus, or cabozantinib in each of those spots, so that at the end patients have received all of those 3 agents. By doing so, you will have ensured that your patients have received the best published proven therapy to date.

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