Sunitinib objective response in metastatic renal cell carcinoma: analysis of 1059 patients treated on clinical trials.
BACKGROUND
Retrospective analyses were performed in patients with metastatic renal cell carcinoma (mRCC) to characterise the objective response (OR) rate to sunitinib and differentiate pretreatment features and outcomes of patients with early (response by ≤ 12 weeks) versus late response, and responders versus non-responders.


METHODS
Data were pooled from 1059 patients in six trials. Median progression-free survival (PFS) and overall survival (OS) were estimated by Brookmeyer and Crowley method and compared between groups by log-rank test. Baseline characteristics were compared by Fisher-exact, t-, or Wilcoxon rank-sum tests. Associations between characteristics and survival were investigated by Cox proportional regression analysis.


RESULTS
398 patients (38%) had confirmed OR (12 complete responses); 26%, 61%, 79% and 86% responded by 6, 12, 18 and 24 weeks, respectively. Median (range) time to tumour response (TTR) was 10.6 (2.7-94.4) weeks and was similar in treatment-naïve and cytokine-refractory patients. Median response duration in early and late responders was 52.0 and 55.0 weeks, respectively. Median PFS in early versus late responders was 13.8 versus 20.2 months (P=0.001); however, median OS did not significantly differ (37.8 versus 40.8 months; P=0.144). Early responders had more lung metastases (P<0.01), but baseline characteristics were otherwise mostly similar. Median PFS (16.3 versus 5.3 months) and OS (40.1 versus 14.5 months) were longer in responders versus non-responders (both P<0.001); responders had more favourable prognostic factors.


CONCLUSIONS
OR occurred in 38% of sunitinib-treated mRCC patients. Sixty-one percent of responses occurred by 12 weeks of therapy, and responders had favourable pretreatment features and significantly longer survival.
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA.
A M
AM
Molina
Pfizer Oncology, 10555 Science Center Drive, La Jolla, CA 92121, USA.
X
X
Lin
Pfizer Oncology, 235 E 42nd St, New York, NY 10017, USA.
B
B
Korytowsky
Pfizer Oncology, 235 E 42nd St, New York, NY 10017, USA.
E
E
Matczak
Pfizer Oncology, Pfizer Italia Srl, Via Lorenteggio 257, Milan 20152, Italy.
M J
MJ
Lechuga
Pfizer Oncology, Walton Oaks, Tadworth KT20 7NS, UK.
R
R
Wiltshire
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. Electronic address: motzerr@mskcc.org.
R J
RJ
Motzer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007211:Indoles; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D011758:Pyrroles; D012189:Retrospective Studies; D000077210:Sunitinib; D055815:Young Adult
D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
Metastatic renal cell carcinoma; Objective response; Sunitinib