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November 16, 2017

On November 16, 2017, the Food and Drug Administration approved sunitinib malate (Sutent, Pfizer Inc.) for the adjuvant treatment of adult patients at high risk of recurrent renal cell carcinoma following nephrectomy.

Approval was based on a multi-center, international, double-blind, placebo-controlled, trial (S-TRAC), in 615 patients with high risk of recurrent RCC following nephrectomy. Patients were randomized 1:1 to receive either 50 mg sunitinib malate once daily, 4 weeks on treatment followed by 2 weeks off, or placebo. Median disease-free survival for patients taking sunitinib malate was 6.8 years (95% CI: 5.8, not reached) compared with 5.6 years (95% CI: 3.8, 6.6) for patients receiving placebo (HR=0.76; 95% CI: 0.59, 0.98; p=0.03). At the time of DFS analysis, overall survival data were not mature.

The most common adverse reactions (≥25%) to sunitinib malate are fatigue/asthenia, diarrhea, mucositis/stomatitis, nausea, decreased appetite/anorexia, vomiting, abdominal pain, hand-foot syndrome, hypertension, bleeding events, dysgeusia/altered taste, dyspepsia, and thrombocytopenia. The labeling contains a boxed warning to alert healthcare professionals and patients about the risk of hepatoxicity, which may result in liver failure or death.

The recommended dose of sunitinib malate for the adjuvant treatment of RCC is 50 mg orally once daily, with or without food, 4 weeks on treatment followed by 2 weeks off for nine 6-week cycles.

Full prescribing information is available at:

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).


Pharmacist's Applications to Practice

Sunitinib (Sutent) for Adjuvant Treatment of Adult Patients at High Risk of Recurrent Renal Cell Carcinoma Following Nephrectomy

Author: Rebecca Martin, PharmD
PGY-1 Pharmacy Resident
WVU Medicine
Morgantown, WV

What is the potential role of sunitinib in the treatment of adjuvant renal cell carcinoma1-9?

  • Sunitinib was approved by the U.S. Food and Drug Administration (FDA) for treatment of renal cell carcinoma (RCC) in the adjuvant setting in November 2017. The approval was based on improved disease-free survival (DFS) from the S-TRAC study, which analyzed outcomes of 615 patients with locoregional clear-cell RCC at high risk of relapse following a nephrectomy who were randomized to receive sunitinib versus placebo.
  • Sunitinib had previously been studied in the ASSURE trial, which evaluated sunitinib, sorafenib, and placebo for use in the adjuvant setting in patients (N = 1,943) at high risk of relapse.
    • Neither the primary end point of DFS for all patients with RCC nor the secondary end points of overall survival (OS) and DFS specifically for the clear-cell RCC subgroup were clinically or statistically significant.
  • After the S-TRAC study was published, the ASSURE study provided an updated subset analyses for a similar population included in the S-TRAC study (clear-cell RCC patients with T3 or greater +/- nodal involvement). However, they were still unable to detect any significant differences in DFS or OS between sunitinib or sorafenib versus placebo.
  • The findings and differences between the ASSURE and S-TRAC trials are summarized in Table 1.
  • Sunitinib is a category 1 recommendation for first-line treatment of metastatic RCC by the National Comprehensive Cancer Network (NCCN) guidelines. For the adjuvant treatment setting, sunitinib is listed as a category 2B recommendation in the NCCN guidelines for the treatment of patients with clear-cell RCC stage II or III who are at high risk of relapse postnephrectomy.
  • One third of patients with stage II or III RCC have a 40% chance of relapse after nephrectomy. Currently no additional adjuvant treatment options are recommended in this setting, and enrollment in a clinical trial or surveillance is preferred. Girentuximab and pazopanib did not result in improved outcomes when studied in the adjuvant setting, in the ARISER and PROTECT studies, respectively.

Table 1. Comparison of the ASSURE and S-TRAC Trials

sunitinib table comparison pap

AEs = adverse events; ccRCC = clear-cell renal cell carcinoma; CI = confidence interval; DFS = disease-free survival; ECOG = Eastern Cooperative Oncology Group; HR = hazard ratio; mg = milligram; nccRCC = non-clear-cell renal cell carcinoma; OS = overall survival; UISS = UCLA Integrated Staging System.

What role can the pharmacist play in the management of patients on sunitinib?2,5,6

  • Counsel patients on the importance of adherence and on the administration schedule for sunitinib.
    • Dose 50 mg once daily for cycle of 4 weeks on and 2 weeks off (same dosing used in metastatic RCC).
      • Dose reductions may be necessary if the regimen cannot be tolerated. In practice, a cycle of 2 weeks on/1 week off may be better tolerated. However, published data for this approach are limited.
      • This dosing schedule contrasts with the 37.5 mg daily continuous dosing approved for treatment of neuroendocrine tumors.
  • Monitor for drug-drug interactions and recommend safe and effective therapeutic alternatives.
    • Avoid concomitant use of strong cytochrome P450 3A (CYP3A) inhibitors or inducers.
      • Inhibitors: consider dose reductions to a minimum of 37.5 mg daily if interaction cannot be avoided.
      • Inducers: consider dose increase to a maximum of 87.5 mg daily if interaction cannot be avoided.
    • Avoid use with other agents that may prolong QTc interval and closely monitor.
  • Counsel patient that drug can be taken with or without food but that grapefruit juice should be avoided.
  • Monitor for and counsel patients on the following signs and symptoms, warnings, and precautions:
    • Adverse reactions (all grades): neutropenia (72%), thrombocytopenia (64%), stomatitis (61%), decreased appetite (59%), asthenia (57%), epistaxis (55%), nausea (34%), rash (24%), hypothyroidism (24%), hair color change (22%), vomiting (19%), and headache (19%)
    • Grade 3+ effects: hand-foot syndrome (HFS) (16%), neutropenia (8.5%), hypertension (7.8%), and thrombocytopenia (6.2%)
      • Grade 3+ HFS reported was 16% versus 5% in the adjuvant and metastatic studies, respectively.
    • Sunitinib carries a black-box warning for hepatotoxicity; however, significant hepatotoxicity was not observed in the S-TRAC and ASSURE studies. Patients with serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 2.5 x upper limit of normal (ULN) or total bilirubin > 1.5 x ULN were excluded from enrollment.
  • The Pfizer Patient Assistance Program is also available for those who are uninsured or cannot afford the co-pays. This program provides co-pay assistance cards for patients with commercial insurance. More information can be found at

Clinical Pearls1,2,5,6

  • Consider the risks and benefits of initiating sunitinib in a patient at high risk of relapse postnephrectomy. Sunitinib has had improved DFS and OS outcomes illustrated in the metastatic setting but less clinically significant findings in the adjuvant setting.
    • Conflicting results of the ASSURE and S-TRAC trial may be due to differences in study design.
    • Adjuvant sunitinib is associated with increased adverse effects, specifically HFS, and higher treatment discontinuation rates when compared with use in the metastatic setting.
  • A subgroup analysis and OS update for the S-TRAC trial was published in September 2017. Patients less than 45 years of age, normal weight, Eastern Cooperative Oncology Group 0, Fuhrman G3-4 tumors, higher risk and neutrophil-to-lymphocyte ratio less than 3 were found to have extended DFS, which may shed light on patient populations more likely to benefit from adjuvant sunitinib in clinical practice.


  1. National Comprehensive Cancer Network. Kidney Cancer (Version 3.2018) Accessed March 19, 2018.
  2. Sutent (sunitinib) [package insert]. New York, NY: Pfizer Labs; 2011.
  3. Barata PC, Rini B. Treatment of renal cell carcinoma: current status and future directions. CA Cancer J Clin. 2017;67(6):507-524.
  4. Susman E. Renal cell relapse possible years later. Oncology Times. 2016;38(6):20.
  5. Ravaud A, Motzer RJ, Pandha HS, et al. Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med. 2016;375:2246-2254.
  6. Motzer RJ, Ravaud, Patard JJ, et al. Adjuvant sunitinib or high-risk renal-cell carcinoma after nephrectomy: subgroup analyses and updated overall survival results. Eur Urol. 2018;73(1):62-68.
  7. 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, randomized, phase 3 trial. Lancet. 2016;387(10032):2008-2016.
  8. Escudier B, Porta C, Bono P, et al. Randomized, controlled, double-blind, cross-over trial assessing treatment preference for pazopanib versus sunitinib in patients with metastatic renal cell carcinoma: PISCES Study. J Clin Oncol. 2014;32(14):1412-1418.
  9. Motzer RJ, Hutson RE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013;369(8):722-731.