Randomized phase II trial of first-line treatment with sorafenib versus interferon in patients with advanced renal cell carcinoma: Final results

Abstract

5025 Background: This trial investigated the efficacy and safety of sorafenib (SOR) vs interferon (IFN) in treatment-naïve patients with clear-cell renal cell carcinoma (RCC). Methods: Previously untreated patients with advanced RCC were randomized to continuous oral SOR 400 mg bid or IFN 9 million units tiw (part 1), with an option of dose escalation to SOR 600 mg bid or crossover from IFN to SOR 400 mg bid upon disease progression (part 2). The primary endpoint was progression-free survival (PFS). Results: Baseline characteristics (ITT, n=189) were similar in SOR (n=97) and IFN (n=92) groups. In the IFN arm, 90/92 patients received treatment; 56 had disease progression, of which 50 crossed to SOR. All 97 patients in the SOR arm received SOR 400 mg bid; 65 had disease progression, of which 44 were dose escalated to 600 mg bid. In part 1, 5% vs 9% patients had complete/partial response, disease control rate (complete/partial response + stable disease) was 79% vs 64%, and median PFS was 5.7 months (CI: 5.0–7.4 months) vs 5.6 months (CI: 3.7–7.4 months) for SOR vs IFN, respectively. Progression-free rates for SOR vs IFN were 90.0% vs 70.4%, 45.9% vs 46.5%, and 11.5% vs 30.4% at 3, 6, and 12 months, respectively. A total of 11% vs 15% of patients receiving SOR or IFN, respectively, discontinued due to adverse events. Overall, the incidence of adverse events was similar between both treatment arms, although skin toxicity (rash and hand-foot skin reaction) and diarrhea occurred more frequently in the SOR group, and flu-like syndrome occurred more frequently in the IFN group. In part 2, median PFS was 5.3 months (CI: 3.6–6.1 months) in patients (n=50) who crossed from IFN to SOR. The median PFS for patients (n=44) with dose escalation to 600 mg bid was 3.6 months (CI: 1.9–5.3 months). The 600 mg bid dose was well tolerated. Conclusions: Although the primary endpoint (PFS) was not reached, SOR showed activity in first-line treatment of RCC based on disease control rate. PFS benefit was observed in patients who crossed to SOR 400 mg bid after progression on IFN. Patients who were dose escalated to 600 mg bid after progression had disease stabilization for a further 3.6 months. Further analyses of possible benefit from SOR dose escalation are required in a larger number of patients. [Table: see text]

Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice‐based on medical chart review

“…Our estimates of median PFS for patients treated with sunitinib (15.3 months), sorafenib (6.9 months) or bevacizumab (9.5 months) are somewhat higher than the previously reported results of a median PFS of 11, 5.7 and 8.5 months for sunitinib, sorafenib, and bevacizumab, respectively [5,6,8,14]. However, the PFS in our study might be overestimated because re‐staging studies might not be performed as frequently or at predefined disease assessment schedules as in clinical trials.…”

“…Of patients treated with sunitinib, sorafenib and bevacizumab, 7% (4/57), 6% (4/62) and 12% (3/25) respectively, had an ECOG score of 2, and 19% (11/57), 13% (8/62) and 4% (16/52) of these patients had brain metastases before starting anti‐angiogenic treatment, both of which are common exclusion criteria in clinical trials of angiogenesis inhibitors [5,8,10,14].…”

“…[15] found that previously defined risk factors for mRCC, including better PS and fewer metastatic sites, predicted a longer PFS with sunitinib. Findings from the ‘Advanced Renal Cell Carcinoma Sorafenib Expanded Access Trial’ suggested that the efficacy and safety of sorafenib in patients with brain metastasis was similar to that in patients without brain metastasis [14].…”

Renal Cell Carcinoma: New Developments in Molecular Biology and Potential for Targeted Therapies

“…With the observed benefit of sorafenib in patients refractory to first-line therapy (mostly immunotherapy) from the TARGET trial, sorafenib was compared with IFN-␣ in untreated patients in a randomized phase II trial. Contrary to what was expected, the objective response rate was only 5% in patients receiving sorafenib, with no advantage over IFN-␣ in terms of response rate or PFS duration (5.7 versus 5.6 months) [56]. However, from the large sorafenib open-access program, there were 224 previously untreated patients for whom the PFS duration was 35 weeks [57].…”

Recent advances in molecular targeted therapy for metastatic renal cell carcinoma

“…Based on the data above, RCT on sorafenib (n = 97) versus IFN-a (n = 92) as the first-line therapy for patients with metastatic RCC was shown. 14 The histological type of RCC was clear cell type. Antitumor response rates were 5% and 9% in the sorafenib-treated and IFN-atreated groups, respectively.…”