Minimizing Toxicity While Maintaining Efficacy in RCC - Episode 11

Case Study: Utilizing Multiple Therapies in mRCC

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Nizar M. Tannir, MD, discusses a case involving a 62 year-old Hispanic male who presented with drenching night sweats, nausea, and vomiting. He was found to have a right renal mass with bilateral lung metastasis, and a biopsy confirmed clear-cell histology. The patient was enrolled in a clinical trial with sunitinib 50 mg daily, 4 weeks on, 2 weeks off. During the second cycle, he underwent a right radical nephrectomy and retroperitoneal lymph node dissection. Postoperatively, sunitinib treatment was resumed. The dose was reduced to 37.5 mg due to some adverse events (fatigue, nausea, vomiting, and hypertension). The patient had a good response for 3 years, but then progressed at his site of metastasis (the lungs).

Following progression, the patient was enrolled in the phase III trial comparing the anti-PD-1 drug nivolumab versus everolimus. After receiving everolimus 10 mg daily, he had disease progression in the lungs. One month later, he began therapy with axitinib, 5 mg twice daily. He has still showed progression in the lungs, but now has a good performance status, says Tannir.

Moderator Robert Figlin, MD, asked the panel to comment on whether every patient with renal cell carcinoma (RCC) needs every drug, and the point at which it might be appropriate to try drugs that are still in phase I clinical trials.

Daniel J. George, MD, says that it is best to keep treating patients who maintain their performance status and tolerance to therapy. These drugs are not clones of each other, he says. There have been cases where a patient progresses on one or more VEGF TKI, but responds to another one. Trying a drug like sorafenib or a drug like pazopanib off-study is off-label at this point, representing a potential reimbursement challenge. There are some patients who might be good candidates for phase I studies, however.

Figlin adds that it might be appropriate to try sorafenib in patients with VEGF-dependent disease who have not responded to other agents. Not all patients end up on second-line or third-line therapies. George comments that a longer term response with a VEGF TKI like sunitinib in a patient suggests other VEGF TKIs might result in a stabilizing effect. In this setting, stable disease can be very clinically meaningful.