Real-world use of sunitinib in Japanese patients with advanced renal cell carcinoma: efficacy, safety and biomarker analyses in 1689 consecutive patients.
OBJECTIVE
This prospective, post-marketing study collected sunitinib safety and efficacy data in Japanese patients with unresectable/metastatic renal cell carcinoma. Retrospective analysis investigated adverse events as potential sunitinib efficacy biomarkers.


METHODS
Patients administered sunitinib, after its release, were registered until reaching a pre-specified number of cases. Primary starting dose was 50 mg/day orally on a 4-weeks-on and 2-weeks-off schedule. Physicians completed investigation forms at 6-week intervals for 24 weeks. Associations between baseline characteristics and adverse events were analyzed by Cox proportional hazards model and compared by χ(2) test. The log-rank test compared survival in subpopulations based on selected factors.


RESULTS
Of note, 1689 patients receiving sunitinib were registered between June 2008 and November 2009. Most of them were males (75%), aged <65 years (56%), and had Eastern Cooperative Oncology Group performance status 0/1 (90%), metastatic disease (88%) and previous systemic therapy (66%). Grade ≥ 3 adverse events occurred in 70%, with reduced platelet count the most common (34%). Characteristics significantly associated with Grade ≥ 3 adverse events were female sex, age ≥ 55 years, Eastern Cooperative Oncology Group performance status ≥ 2, history of several medical conditions and prior treatment. Objective response rate was 22%. Median progression-free survival was 22.7 weeks. Median overall survival was not reached; however, 24-week overall survival rate was 84%. Improved overall survival was associated with higher relative dose intensity during the first 6 weeks and specific adverse events: hypertension, hand-foot syndrome, hypothyroidism, leukopenia and thrombocytopenia.


CONCLUSIONS
Sunitinib demonstrated acceptable safety and useful efficacy in Japanese patients with unresectable/metastatic renal cell carcinoma. Potential biomarkers associated with greater efficacy were relative dose intensity and specific adverse events.
Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo.
Hideyuki
H
Akaza
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
Seiji
S
Naito
Pfizer Japan, Tokyo, Japan.
Naomi
N
Ueno
Pfizer Japan, Tokyo, Japan.
Kouji
K
Aoki
Pfizer Japan, Tokyo, Japan.
Hiroyuki
H
Houzawa
Pfizer Oncology, New York, NY, USA.
Susan
S
Pitman Lowenthal
Pfizer Japan, Tokyo, Japan sang-yoon.lee@pfizer.com.
Sang-Yoon
SY
Lee
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People / Q000706:statistics & numerical data; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007564:Japan; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011358:Product Surveillance, Postmarketing; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib
Japanese; biomarkers; real world; renal cell carcinoma; sunitinib