Cessation of VEGF-targeted therapy in patients with metastatic renal cell carcinoma (mRCC): Feasibility and clinical outcome.
307 Background: Standard practice in the treatment (tx) of mRCC with VEGF targeted agents is continuous tx until progression of disease (PD) or unacceptable toxicity. Chronic mild to moderate toxicity and risk of long-term toxicity ensue for a subset of pts. It is hypothesized that a subset of pts with an initial response to tx can maintain disease control off all tx for a period of time. Methods: A retrospective study of mRCC pts who initiated VEGF-targeted tx between January 2004 and November 2009 was conducted. Pts had achieved disease control on tx, then were taken off all tx. Pt, disease and tx characteristics were recorded. Progression free survival (PFS) was measured as the time from discontinuation of tx to RECIST PD. Results: A total of 30 pts were identified. All pts had prior nephrectomy and had clear cell histology, and 9 patients had prior immunotherapy. At the time tx was stopped 16 pts were receiving sunitinib, 7 pts were receiving sorafenib (2 in combination with AMG 386), and 7 pts were receiving bevacizumab (6 in combination with temsirolimus, 1 with IFN-alpha). Six pts had achieved CR, 19 PR and 5 SD by RECIST. Using Heng's prognostic risk group criteria, 14 pts had favorable, 14 had intermediate, and 2 had poor risk disease prior to initiation of VEGF-targeted tx. Therapy was held for severe adverse events (5pts; 2 MIs, 3 CVAs), toxicity (16 pts; 4 diarrhea, 3 skin, 3 proteinuria, 2 cardiac, 1 fatigue, 1 stomatitis, 1 pneumonitis, 1 nausea), cost (1 pt; high co-pay), pt choice (6 pts) and interventions (2 pts; 1 angioplasty and 1 kidney stone). Median follow up is 29 months (range 11– 82). Median duration of tx prior to discontinuation was 14.6 months (range 3–79). Thirteen pts (43%) had PD off tx (lymph nodes (6), lungs (8; 3 with new lesions), bones (1), brain (2; 1 with new lesions)) with a median PFS of 10 months (range 3–27). After PD, 4 pts were offered sunitinib, 1 pazopanib, 1 everolimus, 1 local RF tx, and 6 continued expectant management. After a median follow-up to date of 7.5 months (2–28), 17 pts (57%) still did not have RECIST PD. Conclusions: Select mRCC pts with disease control on VEGF-targeted tx can be safely observed off all tx. Further prospective investigation is needed to define the risks and benefits of this approach. [Table: see text]