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Annals of Oncology
J.D. Powderly: Consultant or Advisory Role: MedicineX and Bristol-Myers Squibb
(myself, compensated). Research Funding: Bristol-Myers Squibb (clinical trials
funding, myself). Honoraria: Bristol-Myers Squibb (ipilimumab speakers bureau,
myself). D.C. Smith: Research Funding: Bristol-Myers Squibb Oncology (myself). J.
M. Wigginton: Employment or Leadership Role: Bristol-Myers Squibb (employment,
myself, compensated). Stock Ownership: Bristol-Myers Squibb (myself). G. Kollia:
Employment or Leadership Role: Bristol-Myers Squibb (employment, myself,
compensated). Stock Ownership: Bristol-Myers Squibb (BMY) (myself). A. Gupta:
Employment or Advisory Role: Bristol-Myers Squibb (employment, myself,
compensated). Stock Ownership: Bristol-Myers Squibb (myself). M.B. Atkins:
Advisory or Consultant Role: Bristol-Myers Squibb, Curetech, and Merck (myself,
compensated).
785O COMPARATIVE ASSESSMENT OF SUNITINIB-ASSOCIATED
ADVERSE EVENTS (AES) AS POTENTIAL BIOMARKERS OF
EFFICACY IN METASTATIC RENAL CELL CARCINOMA
(MRCC)
F. Donskov 1 , M.D. Michaelson 2 , I. Puzanov 3 , M.P. Davis 4 , G.A. Bjarnason 5 ,
R.J. Motzer 6 , X. Lin 7 , D.P. Cohen 7 , R. Wiltshire 8 , B.I. Rini 9
1 Department of Oncology, Aarhus University Hospital, Aarhus, DENMARK,
2 Medical Oncology, Massachusetts General Hospital Cancer Center, Boston,
MA, UNITED STATES OF AMERICA, 3 Division of Hematology-oncology,
Vanderbilt University Medical Center, Nashville, TN, UNITED STATES OF
AMERICA, 4 Medical Oncology, Cleveland Clinic, Cleveland, OH, UNITED
STATES OF AMERICA, 5 Medical Oncology, Sunnybrook Odette Cancer Centre,
Toronto, CANADA, 6 Genitourinary Oncology Service, Memorial Sloan-Kettering
Cancer Center, New York, NY, UNITED STATES OF AMERICA, 7 Reseach and
Development, Pfizer Oncology, La Jolla, CA, UNITED STATES OF AMERICA,
8 Research and Development, Pfizer Oncology, Tadworth, UNITED KINGDOM,
9 Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic Taussig Cancer
Institute, Cleveland, OH, UNITED STATES OF AMERICA
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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)