Upfront Cytoreductive Nephrectomy Not Needed Before Targeted Therapy in mRCC

For patients with metastatic renal cell carcinoma (mRCC), initial treatment typically includes cytoreductive nephrectomy followed by angiogenesis inhibitor therapy. While retrospective analyses have historically shown that patients who receive a nephrectomy have prolonged survival compared to those who do not, no study has directly compared nephrectomy and targeted therapy in patients newly diagnosed with mRCC. To determine if cytoreductive nephrectomy adds therapeutic value in the era of targeted therapy, the phase III CARMENA noninferiority trial (N = 450) compared sunitinib alone to cytoreductive nephrectomy followed by sunitinib in patients newly diagnosed with mRCC. Results from this trial were presented at the plenary session of 2018 Amercian Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine.

At median follow-up of 50.9 months, the median overall survival (OS) was 18.4 months in the sunitinib alone arm, compared to 13.9 months in the nephrectomy plus sunitinib arm (HR 0.89). Similar OS benefits were observed with sunitinib in intermediate and poor risk populations. The median progression-free survival (PFS) was 7.2 months for patients receiving sunitinib versus 8.3 months for patients receiving nephrectomy and sunitinib (HR 0.82). While the overall response rate (ORR) was similar between the two treatment arms (27.4% vs 29.1%), sunitinib alone was associated with a greater clinical benefit rate than nephrectomy plus sunitinib (47.9% vs 36.6%; P = .022).

Presenter Arnaud Mejean, MD, PhD (Paris Descartes University, Paris, France) concluded that sunitinib alone has greater clinical benefit than cytoreductive nephrectomy plus sunitinib and that cytoreductive nephrectomy should no longer be considered standard of care in mRCC. Discussant Daniel George, MD (Duke Cancer Institute, Durham, North Carolina, United States), agreed that these results are likely practice changing, but cautioned that cytoreductive nephrectomy may still offer a valuable therapeutic option for patients with low-volume disease and that future trials should evaluate the benefit of immediate versus delayed nephrectomy in these patients.

J Clin Oncol. 2018;36(suppl): Abstract LBA3.
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