The Controversial Role of Sunitinib in the Adjuvant Setting

Although sunitinib and other TKIs were clearly the first-line treatment of choice for advanced RCC before immunotherapy became available, the current role of sunitinib in the adjuvant setting is decidedly more controversial.

Continue Reading

In 2017, the FDA approved sunitinib as the first adjuvant treatment for patients at high risk of RCC recurrence after nephrectomy.10 The decision was based on data from the phase 3 S-TRAC trial, which randomly assigned 615 high-risk patients to receive sunitinib or placebo following nephrectomy.11 The trial reported longer duration of disease-free survival (DFS), 6.8 years, with sunitinib, compared with 5.6 years in the placebo group.

But a larger phase 3 trial, ASSURE, which included 1943 patients, did not find a DFS benefit with sunitinib or another TKI, sorafenib, compared with placebo.12 Rates of grade 3 or 4 adverse events were also high with sunitinib in both the S-TRAC (60.5% of patients) and ASSURE trials (63%), as well as with sorafenib in the ASSURE trial (72%), compared with placebo (19.4% in S-TRAC and 25% in ASSURE). To date, the median OS has not been reached in either trial.

The bigger message, according to Naomi B. Haas, MD, of the University of Pennsylvania in Philadelphia, first author on an updated analysis of ASSURE, is that these trials do not show a benefit in OS.13 Although it will be important to find out the median OS when it is reached, Dr Haas doubts it will be longer in the treatment groups.

Related Articles

Even in S-TRAC, the benefit in DFS was only about a year, which is about the length of time that patients were on the drug and likely experiencing side effects from the drugs. “That’s a lot to ask of patients receiving adjuvant therapy to, number one, have a lot of side effects, and number two, not see a benefit in OS,” Dr Haas said.

Nevertheless, there may be some patients for whom sunitinib could be appropriate in the adjuvant setting, she added. These include patients who are not candidates for a clinical trial, such as with a checkpoint inhibitor, or patients who have a very high risk of recurrence.

For his part, Dr McGregor said, “it is something that we need to discuss with patients as an option of doing something, but it involves a very informed discussion with the patient about the risk of therapy.”


  1. Motzer RJ, Escudier B, Gannon A, Figlin RA. Sunitinib: ten years of successful clinical use and study in advanced renal cell carcinoma. Oncologist. 2017;22(1):41-52. doi: 10.1634/theoncologist.2016-0197
  2. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115-24.
  3. FDA approves sunitinib malate for adjuvant treatment of renal cell carcinoma [news release]. Silver Spring, MD: US Food and Drug Administration; November 16, 2017. Accessed April 2018.
  4. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277-90. doi: 10.1056/NEJMoa1712126
  5. Xu JX, Maher VE, Zhang L, et al. FDA approval summary: nivolumab in advanced renal cell carcinoma after anti-angiogenic therapy and exploratory predictive biomarker analysis. Oncologist. 2017;22(3):311-7. doi: 10.1634/theoncologist.2016-0476
  6. Motzer RJ, Jonasch E, Agarwal N, et al. Kidney cancer, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017;15(6):804-4. doi: 10.6004/jnccn.2017.0100
  7. A study of nivolumab combined with cabozantinib compared to sunitinib in previously untreated advanced or metastatic renal cell carcinoma (CheckMate 9ER). NCT03141177. Accessed April 2018.
  8. Lenvatinib/everolimus or lenvatinib/pembrolizumab versus sunitinib alone as treatment of advanced renal cell carcinoma (CLEAR). NCT02811861. Accessed April 2018.
  9. Nivolumab (BMS-936558; MDX-1106) in combination with sunitinib, pazopanib, or ipilimumab in subjects with metastatic renal cell carcinoma (RCC) (CheckMate 016). NCT01472081. Accessed April 2018.
  10. FDA approves sunitinib malate for adjuvant treatment of renal cell carcinoma [news release]. Silver Spring, MD: US Food and Drug Administration; November 16, 2017. Accessed April 2018.
  11. Ravaud A, Motzer RJ, Pandha HS, et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 2016;375(23):2246-54.
  12. Haas NB, Manola J, Uzzo RG, et al. Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet. 2016;387(10032):2008-16. doi: 10.1016/S0140-6736(16)00559-6
  13. Haas NB, Manola J, Dutcher JP, et al. Adjuvant treatment for high-risk clear cell renal cancer: updated results of a high-risk subset of the ASSURE randomized trial. JAMA Oncol. 2017;3(9):1249-52. doi: 10.1001/jamaoncol.2017.0076