Phase 2 trials of SU11248 show antitumor activity in second-line therapy for patients with metastatic renal cell carcinoma (RCC)

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Abstract
4508 Background: SU11248 is an oral multi-targeted tyrosine kinase inhibitor of PDGFR and VEGFR with antiangiogenic and antitumor activity. Methods: Antitumor activity against metastatic RCC has been studied in 2 independent single-arm trials. Eligibility for both trials included measurable disease, failure of one prior cytokine therapy, and adequate organ function. Repeat cycles of SU11248 were given orally at 50 mg daily for 4 weeks followed by a 2-week rest period. Best response was assessed by RECIST. Trial 1 accrued 63 pts from 1/03 to 7/03 and Trial 2 accrued 106 pts from 2/04 through 11/04. Results: Of 63 pts enrolled in Trial 1, 25 (40%) pts achieved a partial response (PR) (95% CI: 28%, 53%), 21 (33%) pts had stable disease, and 17 (27%) pts had progression as best response. Of 25 pts who achieved a PR, the median duration of response is 10+ months (range 2 - 19+); 9 remain progression-free (including 2 PRs rendered disease-free by surgery [surgical complete responses (CRs)]); and 5 show continuous response of >12 months duration. The median time to progression (TTP) is 8.3 months, the median survival is 16 months, and 9 pts remain on therapy. Adverse events were mostly grade 1 and 2 and included fatigue, nausea, diarrhea, and stomatitis. Of 106 pts enrolled in Trial 2, 83 have completed at least 2 cycles of treatment and are assessable for response; it is too early to assess the remaining 23 pts. In this preliminary report, 24 (29%) of the 83 assessable pts have ≥30% decrease in tumor size by RECIST including 1 with a CR, 16 with confirmed PR, and 7 awaiting confirmation of PR status. Conclusions: Two consecutively conducted phase II trials in 169 pts show that SU11248 has substantial antitumor activity as second-line therapy for pts with metastatic RCC. The PR proportion of 40%, TTP of 8.3 months and median survival of 16 months observed in Trial 1 are particularly noteworthy when compared to prior studies of second-line therapy in RCC (JCO 2004;22:454). Trial 2 has confirmed anti-tumor activity in an independent group of patients and, having completed accrual, seeks to validate the degree of efficacy observed in the earlier study.

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