Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients.
BACKGROUND
Metastatic renal cell carcinoma (mRCC) prognostic models may be improved by incorporating treatment-induced toxicities.


METHODS
In sunitinib-treated mRCC patients (N=770), baseline prognostic factors and treatment-induced toxicities (hypertension (systolic blood pressure ⩾140 mm Hg), neutropenia (grade ⩾2), thrombocytopenia (grade ⩾2), hand-foot syndrome (grade >0), and asthenia/fatigue (grade >0)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points.


RESULTS
On-treatment neutropenia and hypertension were associated with longer PFS (P=0.0276 and P<0.0001, respectively) and OS (P=0.0014 and P<0.0001, respectively), independent of baseline prognostic factors, including International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. By 12-week landmark analysis, neutropenia was significantly associated with longer PFS and OS (P=0.013 and P=0.0122, respectively) and hypertension or hand-foot syndrome with longer OS (P=0.0036 and P=0.0218, respectively). The concordance index was 0.65 (95% CI: 0.63-0.67) for IMDC classification alone and 0.72 (95% CI: 0.70-0.74) when combined with hypertension and neutropenia. Considering hypertension and neutropenia (developing both vs neither) changed IMDC-predicted median OS in each IMDC risk group (favourable: 45.3 vs 19.5 months; intermediate: 32.5 vs 8.0 months; poor: 21.1 vs 4.8 months).


CONCLUSIONS
On-treatment neutropenia and hypertension are independent biomarkers of sunitinib efficacy and may add prognostic accuracy to the IMDC model.
Department of Oncology, Aarhus University Hospital, Norrebrogade 44, Aarhus C 8000, Denmark.
Frede
F
Donskov
Massachusetts General Hospital Cancer Center, The Claire and John Bertucci Center for Genitourinary Cancers, 55 Fruit Street, Yawkey 7E, Boston, MA 02114, USA.
M Dror
MD
Michaelson
Division of Hematology-Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37232-6307, USA.
Igor
I
Puzanov
Palliative Medicine and Supportive Oncology Services, Division of Solid Tumor, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Avenue, Desk R35, Cleveland, OH 44195, USA.
Mellar P
MP
Davis
Division of Medical Oncology, Sunnybrook Odette Cancer Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
Georg A
GA
Bjarnason
Department of Medicine, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Robert J
RJ
Motzer
Department of Medical Oncology, Prince of Wales Hospital, Randwick, NSW 2031, Australia.
David
D
Goldstein
Pfizer Oncology, 10646 Science Center Drive, La Jolla, CA 92121, USA.
Xun
X
Lin
Pfizer Oncology, 10646 Science Center Drive, La Jolla, CA 92121, USA.
Darrel P
DP
Cohen
Pfizer Oncology, Walton Oaks, Dorking Road, Walton-on-the-Hill, Tadworth, Surrey KT20 7NS, UK.
Robin
R
Wiltshire
Cleveland Clinic Taussig Cancer Institute, Glickman Urological Institute, 9500 Euclid Avenue, Desk R35, Cleveland, OH 44195, USA.
Brian I
BI
Rini
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D015996:Survival Rate; D055815:Young Adult
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib