Sorafenib plus interferon-α2b (IFN) as first-line therapy for advanced renal cell carcinoma (RCC): SWOG 0412

Abstract

4525 Background: Sorafenib is a RAF and multiple receptor tyrosine kinase inhibitor active in RCC. IFN has modest activity in RCC and has immunologic, anti-angiogenic, and anti-proliferative effects. Sorafenib and IFN may simultaneously target anti-angiogenic and MAP kinase pathways, providing the basis for this phase II combination study. Methods: Eligible patients (pts) had metastatic or unresectable RCC with a clear cell component, no prior systemic therapy, performance status 0–1, measurable disease. Treatment: IFN 10 x 106 IU s.c. 3x/week and sorafenib 400 mg p.o. BID. Response assessment was performed q8 weeks. This was a single-stage trial with a planned sample size of 55. Primary endpoint was RECIST response rate. Results: Of 67 registered pts, 58 are eligible & evaluable. Pt characteristics: median age 61 years (42–84), male:female (40:18), prior nephrectomy 86%. MSKCC prognostic categories (42 pts) were good:intermediate:poor (28%:67%:5%). With a median follow-up of 6.5 months, 79% (46/58) of pts are alive, 41% (24/58) remain on treatment. Assessment of progression-free survival is premature. Overall response rate (53 pts) is 19% (95% CI: 9%, 32%) with CR 2% and PR 17% (9% confirmed, 8% unconfirmed). Toxicities affecting >50% of subjects were: fatigue, anorexia, diarrhea, nausea, rigors/chills, fever, anemia, leukopenia. Most common Grade 3+ toxicities were fatigue (24%), leukopenia (10%), anorexia (6%), diarrhea (6%), hyponatremia (6%). All pts experienced some toxicity, with 36 (62%) experiencing at least one Grade 3+ toxicity. Hand-foot syndrome, a common side effect of sorafenib, was seen in only 10% of pts. Conclusions: The overall response rate of 19% for the combination of sorafenib and IFN in advanced RCC is greater than expected with either IFN or sorafenib alone. Toxicity is typical of IFN and notable for minimal hand-foot syndrome. Further studies with this combination are warranted. [Table: see text]