785O - Comparative assessment of sunitinib-associated adverse events (AEs) as potential biomarkers of efficacy in metastatic renal cell carcinoma (mRCC)

Date 01 October 2012
Event ESMO Congress 2012
Session Genitourinary tumors, renal cancer
Topics Anticancer Agents
Renal Cell Cancer
Biological Therapy
Presenter Frede Donskov
Authors F. Donskov1, M.D. Michaelson2, I. Puzanov3, M.P. Davis4, G.A. Bjarnason5, R.J. Motzer6, X. Lin7, D.P. Cohen7, R. Wiltshire8, B.I. Rini9
  • 1Department Of Oncology, Aarhus University Hospital, Aarhus/DK
  • 2Medical Oncology, Massachusetts General Hospital Cancer Center, 02114 - Boston/US
  • 3Division Of Hematology-oncology, Vanderbilt University Medical Center, 37232-6307 - Nashville/US
  • 4Medical Oncology, Cleveland Clinic, Cleveland/US
  • 5Medical Oncology, Sunnybrook Odette Cancer Centre, CA-M4N 3M5 - Toronto/CA
  • 6Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 10021 - New York/US
  • 7Reseach And Development, Pfizer Oncology, La Jolla/US
  • 8Research And Development, Pfizer Oncology, Tadworth/UK
  • 9Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic Taussig Cancer Institute, Cleveland/US



Previous retrospective analyses have separately identified treatment-associated hypertension (HTN), hand–foot syndrome (HFS), asthenia/fatigue (A/F), neutropenia (N), and thrombocytopenia (T) as potential biomarkers of sunitinib efficacy in mRCC patients using a pooled database of five clinical trials (NCT00054886, NCT00077974, NCT00083889, NCT00338884, NCT00137423; Pfizer). We assessed the relative strength and independence of each biomarker in a combined analysis of the same database.


Data from 770 mRCC patients who received sunitinib 50 mg/d on the approved 4-wk-on-2-wk-off schedule (Schedule 4/2; n = 544; 71%) or 37.5 mg/d continuous daily dosing (n = 226; 29%) were included. Combined multivariate analysis, repeated using a 12-wk landmark to address potential bias from longer treatment, was performed (for Schedule 4/2 and both schedules combined). The following were included as covariates for prediction of PFS and OS: previously identified prognostic factors; HTN (SBP ≥140 mmHg); N and T (CTCAE grade >1); and any CTCAE grade HFS and A/F.


HTN, HFS, and A/F remained significant independent biomarkers in sunitinib-treated mRCC patients on Schedule 4/2, with HTN and HFS supported by the strongest data (table). N and T were not significant in any analyses, possibly due to a strong correlation of both with HTN and A/F (P < 0.05; Fisher's exact test), but not with HFS. Dose reduction, adjusted for time on treatment, was not associated with clinical outcome. Results were similar with both schedules combined.


Combined multivariate analyses indicate that HTN and HFS, and to a lesser degree A/F, may serve as independent biomarkers of sunitinib efficacy in mRCC patients. Providers who observe these AEs are therefore encouraged to continue sunitinib therapy, managing AEs with standard medical treatment with or without dose reduction as clinically indicated.

Final multivariate models of associations between AEs and efficacy outcomes for mRCC patients on Schedule 4/2

Efficacy endpoint AE at any time point AE by the 12-wk landmark
HR (95% CI) P* HR (95% CI) P*
HTN during treatment
PFS 0.291 (0.220–0.399) <0.0001 NS
OS 0.296 (0.237–0.427) <0.0001 0.654 (0.511–0.838) 0.0008
HFS during treatment
PFS 0.750 (0.595–0.945 ) 0.0148 NS
OS 0.578 (0.437–0.766) 0.0001 0.674 (0.462– 0.985) 0.0415
A/F during treatment
PFS 0.491 (0.375–0.644) <0.0001 NS
OS 0.720 (0.541–0.959) 0.0245 NS

NS = not significant.

*Wald chi-square test.


F. Donskov: Research funding from Pfizer.

M.D. Michaelson: Advisory relationship with Pfizer. Research funding from Pfizer.

M.P. Davis: Advisory relationship with Pfizer. Research funding from Pfizer.

G.A. Bjarnason: Advisory relationship with Pfizer. Honoraria from Pfizer. Research funding from Pfizer.

R.J. Motzer: Advisory relationship with Pfizer. Research funding from Pfizer.

X. Lin: Employed by Pfizer as an Associate Director and holds Pfizer stock.

D.P. Cohen: Employed by Pfizer as a Senior Director and holds Pfizer stock.

R. Wiltshire: Employed by Pfizer as a Global Medical Affairs Lead and holds Pfizer stock.

B.I. Rini: Advisory relationship with Pfizer. Research funding from Pfizer.

All other authors have declared no conflicts of interest.