Fatigue among patients with renal cell carcinoma receiving adjuvant sunitinib or sorafenib: patient-reported outcomes of ECOG-ACRIN E2805 trial
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E2805 was a phase III trial to test whether adjuvant sunitinib or sorafenib could improve disease-free survival compared to placebo in patients with renal cell carcinoma. Patient-reported outcomes (PRO), focusing on fatigue, were evaluated as a secondary endpoint.
Patients and methods
A total of 463 patients participated in the PRO study. Fatigue was measured by the FACIT Fatigue scale and PROMIS Fatigue SF1 measure at baseline, week 10, and week 22. The primary endpoint was change in fatigue score from baseline to week 22, measured by the FACIT Fatigue scale. Secondarily, the psychometric properties of PROMIS Fatigue SF1 were assessed in relation to the FACIT Fatigue scale.
Fatigue got significantly worse on all arms after 2 cycles of treatment, and especially so in patients on sunitinib (− 9.6 vs. − 5.6 on sorafenib vs. − 4.7 on placebo). Fatigue remained stable during week 10 and week 22. Overall, the mean score change between baseline and week 22 was − 7.9 (p < 0.001) on sunitinib, − 6.4 (p < 0.001) on sorafenib and − 5.6 (p < 0.001) on placebo arm. The difference in score change was not statistically significant between the two experimental arms and the placebo arm (difference = − 2.34 [p = 0.110] and − 0.87 [p = 0.535] for sunitinib vs. placebo and sorafenib vs. placebo). PROMIS Fatigue SF1 had good internal consistency reliability and construct and criterion validity, and was highly correlated with the FACIT Fatigue scale score.
Fatigue got worse during study period, especially in patients on sunitinib. The PROMIS Fatigue SF1 was highly correlated with FACIT Fatigue and produced similar results.
KeywordsFatigue Patient-reported outcome Renal cell carcinoma Adjuvant therapy Sunitinib Sorafenib
The authors thank all the patients who participated in the study.
FZ did the statistical analysis and wrote the first draft of the manuscript. DC and LW designed the quality of life proposal. JM and NBH designed the parent trial as the study statistician and study chair, respectively. RSD was the ECOG-ACRIN Genitourinary committee chair at the time. All authors interpreted the data, reviewed and edited the manuscript drafts, and approved the final version of the manuscript for submission.
This study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: CA180820, CA180794, CA189828. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- 3.Malik UR, Makower DF, Wadler S (2001) Interferon-mediated fatigue. Cancer 92(S6):1664–1668. https://doi.org/10.1002/1097-0142(20010915)92:6+<1664::AID-CNCR1494>3.0.CO;2-9 CrossRefPubMedGoogle Scholar
- 4.Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, Negrier S, Chevreau C, Solska E, Desai AA, Rolland F, Demkow T, Hutson TE, Gore M, Freeman S, Schwartz B, Shan M, Simantov R, Bukowski RM, TARGET Study Group (2007) Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 356(2):125–134. https://doi.org/10.1056/NEJMoa060655 CrossRefPubMedGoogle Scholar
- 5.Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, Oudard S, Negrier S, Szczylik C, Kim ST, Chen I, Bycott PW, Baum CM, Figlin RA (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356(2):115–124. https://doi.org/10.1056/NEJMoa065044 CrossRefGoogle Scholar
- 6.Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, de Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK (2013) Pazopanib versus Sunitinib in metastatic renal-cell carcinoma. N Engl J Med 369(8):722–731. https://doi.org/10.1056/NEJMoa1303989 CrossRefPubMedGoogle Scholar
- 7.Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, Chevreau C, Filipek M, Melichar B, Bajetta E, Gorbunova V, Bay JO, Bodrogi I, Jagiello-Gruszfeld A, Moore N (2007) Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 370(9605):2103–2111. https://doi.org/10.1016/S0140-6736(07)61904-7 CrossRefPubMedGoogle Scholar
- 8.Haas NB, Manola J, Uzzo RG, Flaherty KT, Wood CG, Kane C, Jewett M, Dutcher JP, Atkins MB, Pins M, Wilding G, Cella D, Wagner L, Matin S, Kuzel TM, Sexton WJ, Wong YN, Choueiri TK, Pili R, Puzanov I, Kohli M, Stadler W, Carducci M, Coomes R, DiPaola RS (2016) 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 387(10032):2008–2016. https://doi.org/10.1016/S0140-6736(16)00559-6 CrossRefGoogle Scholar
- 9.Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Martini JF, Ramaswamy K, Casey M, Staehler M, Patard JJ, S-TRAC Investigators (2016) Adjuvant sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med 375(23):2246–2254. https://doi.org/10.1056/NEJMoa1611406 CrossRefPubMedGoogle Scholar
- 12.Gravis G, Marino P, Joly F, Oudard S, Priou F, Esterni B, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Théodore C, Deplanque G, Ferrero JM, Pouessel D, Mourey L, Beuzeboc P, Zanetta S, Habibian M, Berdah JF, Dauba J, Baciuchka M, Platini C, Linassier C, Labourey JL, Machiels JP, el Kouri C, Ravaud A, Suc E, Eymard JC, Hasbini A, Bousquet G, Soulie M, Fizazi K (2014) Patients’ self-assessment versus investigators’ evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15). Eur J Cancer 50(5):953–962. https://doi.org/10.1016/j.ejca.2013.11.034 CrossRefPubMedGoogle Scholar
- 16.Cella D, Eton DT, Lai JS, Peterman AH, Merkel DE (2002) Combining anchor and distribution-based methods to derive minimal clinically important differences on the Functional Assessment of Cancer Therapy (FACT) anemia and fatigue scales. J Pain Symptom Manag 24(6):547–561. https://doi.org/10.1016/S0885-3924(02)00529-8 CrossRefGoogle Scholar
- 17.Yost KJ, Eton DT, Garcia SF, Cella D (2011) Minimally important differences were estimated for six patient-reported outcomes measurement information system-cancer scales in advanced-stage cancer patients. J Clin Epidemiol 64(5):507–516. https://doi.org/10.1016/j.jclinepi.2010.11.018 CrossRefPubMedPubMedCentralGoogle Scholar