Refractory mRCC: Third-Line and Beyond

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Thomas Hutson, DO, PharmD:For our particular patient who went on to receive lenvatinib/everolimus after sunitinib, at the point in which she has progression, I would consider strongly the use of immunotherapy as a third-line, leaving cabozantinib as a fourth-line option for her.

In summary, this patient’s case and unique characteristics provide us a snapshot into real-world management of intermediate-/poor-risk RCC. We see a patient who has multiple sites of disease, who gets started on traditional frontline therapy with sunitinib, has standard or less than standard response, and then moves on to second-line therapy with the combination of lenvatinib and everolimus.

I’ve discussed with you that alternative options, including nivolumab and cabozantinib, would also be considered, and in this particular patient would be employed in the third- and fourth-line setting.

Please understand that treatment options are changing rapidly in RCC. We need these options and we anxiously await the results of ongoing phase III trials. Our goal at the end of the day is to provide our patients with a longer survival, the greatest tolerability, and best quality of life.

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
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