Long-term responders to sunitinib therapy for metastatic renal cell carcinoma (mRCC).

Abstract

4610 Background: Sunitinib has established efficacy in mRCC pts (NEJM 2007; 356:115). We report long-term responders, defined as patients (pts) achieving ongoing complete response (CR) or remaining progression-free for ≥ 18 months on sunitinib. Methods: From 1/03-3/06, 139 pts were treated with sunitinib alone (64 pts) or in combination (75 pts) on 7 clinical trials at MSKCC. Median progression-free survival (PFS) was 11 mos (95% CI 8-15); median OS was 24 mos (95% CI 18-34). 24 of the 139 were identified as long-term responders. Results: Characteristics for the 24 and the entire cohort of 139 were examined (Table). Best response was CR in 3, partial response in 19, and stable disease in 2 pts. Median duration of sunitinib therapy was 26 months (range 18-59) 4 remain on therapy, 15 discontinued for progression, 3 discontinued for toxicity, 1 remains off therapy after CR and 1 discontinued following resection of metastasis. Landmark PFS analysis was performed at 18 months: median PFS was 25 months (95% CI, 11-51 mos); median OS was 38 mos (95% CI 25-51). Grade 3 adverse events after 18 mos of sunitinib included diarrhea (29%), fatigue (17%), hand-foot syndrome (21%); unique late toxicities were not observed. Logistic regression analysis from the 139 pts identified bone metastasis, lung metastasis and ≥2 metastatic sites as adverse prognostic factors for long-term response (Table). Conclusions: Sunitinib achieves long-term response in a subset of pts with mRCC. Prolonged treatment was relatively well tolerated without unique late toxicities. Lack of bone metastasis or lung metastases and one metastatic site may predict long-term response. All Long-term responders Univariate logistic analysis (yes vs. no) (N=139) (N=24) Odds ratio (95% CI) p Sites of disease Bone 38 (27%) 3 (13%) 0.33 (0.09, 1.17) 0.08 Lung 97 (70%) 13 (54%) 0.44 (0.18, 1.08) 0.07 Liver 30 (22%) 4 (17%) 0.69 (0.22, 2.18) 0.52 ≥2 metastatic sites 101 (73%) 14 (58%) 0.45 (0.18, 1.13) 0.09 Prior treatment 72 (52%) 16 (67%) 1.91 (0.75, 4.85) 0.17 Clear cell histology 117 (84%) 21 (88%) 1.39 (0.38, 5.11) 0.62 MSKCC risk group Favorable 72 (52%) 15 (63%) 1.70 (0.69, 4.19) 0.25 Intermediate/poor 67 (48%) 9 (37.5%) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Genentech, Pfizer