Predictors of response to sequential sunitinib and the impact of prior VEGF-targeted drug washout in patients with metastatic clear-cell renal cell carcinoma.
OBJECTIVE
To identify factors that can be used to identify metastatic clear cell RCC patients more likely to benefit from sequential sunitinib.


METHODS
We identified patients who failed sorafenib or bevacizumab and subsequently received sunitinib. We looked at objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) to sunitinib in relation to baseline clinical variables.


RESULTS
Seventy-one patients received sunitinib sequential therapy. Median duration of follow-up after starting sunitinib was 9.3 months. Median PFS was 5.8 months; median OS was not reached. Significantly higher ORR was seen in patients with normal hemoglobin (25.6%) [defined as >12 gm/dl for female; >13 gm/dl for male]. In addition, a shorter PFS for patients with low hemoglobin, and patients with time from diagnosis to first treatment ≤ 1 year was found. There was a shorter OS for patients ≥ 60 years old, with brain metastasis, low hemoglobin, and time from diagnosis to treatment ≤ 1 year. There was no difference in ORR, PFS, or OS in patients who started sunitinib after or within a 30-day period.


CONCLUSIONS
Metastatic clear-cell RCC patients with anemia have less clinical benefit from sequential sunitinib after failure of bevacizumab or sorafenib. Other factors associated with poor outcome include brain metastases, older age, and <1 year between diagnosis and first treatment. Importantly, no difference in outcomes was observed if sequential therapy was initiated within or after 30 days. External validation and prospective evaluation are needed to confirm these findings.
Elfiky
Aymen A
AA
Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, MA 02115, USA.
Cho
Daniel C
DC
McDermott
David F
DF
Rosenberg
Jonathan E
JE
Fortner
Barry
B
Antràs
Lucia
L
Chen
Kristina
K
Sheng Duh
Mei
M
Jayawant
Sujata S
SS
Oh
William K
WK
Atkins
Michael B
MB
Choueiri
Toni K
TK
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000077210:Sunitinib