Anlotinib versus sunitinib as first line treatment for metastatic renal cell carcinoma (mRCC): Preliminary results from a randomized phase II clinical trial.

4565 Background: Anlotinib is a potent oral, small molecular TKI with a favorable safety profile in phase I clinical trial which mainly targets VEGFR1/2/3, FGFR2. This multicenter randomized phase II trial (NCT02072031) compared efficacy and safety of anlotinib and sunitinib as first line treatment in mRCC patients with clear cell being the predominant component. Methods: Patients were randomized in 2:1 to receive anlotinib or sunitinib. Anlotinib was administered at dose of 12 mg once daily for 2 weeks followed by 1 week rest, sunitinib at dose of 50mg once daily for 4 weeks followed by 2 weeks off. The primary endpoint was progression free survival (PFS). Secondary end points included overall survival (OS), overall response rate (ORR), safety. Results: 133 (93 with anlotinib, 40 with sunitinib) patients were enrolled. Data cutoff was May 15, 2015. Both group had similar PFS (11.3 vs. 11.0 months (p = 0.30), ORR (24.4% vs. 23.3%), 6-week disease controll rate (97.8% vs. 93.0%, p = 0.33). OS for both group has not yet reached. Patients treated with anlotinib, as compared with those treated with sunitinib, had a significant less incidence of grade 3 or 4 side effects (28.9% vs. 55.8%, p = 0.0039), especially less grade 3 or 4 thrombocytopenia (0 vs. 11.6%, p = 0.003), neutropenia (0.0 vs. 9.3%, p = 0.009). As for all grades of side effects, anlotinib had less hand-foot syndrome (41.1% vs. 65.1%, p < 0.015), eyelid edema (2.2% vs. 25.4%, p < 0.0001), hair depigmentation (0.0% vs. 14.0%, p = 0.0009), skin yellowing (0.0 vs. 37.2%, p < 0.0001), neutropenia (3.3% vs. 44.2%, p < 0.0001), thrombocytopenia (11.1% vs. 58.1%, p < 0.0001), anemia (4.4% vs. 34.9%, p < 0.001). Also, anlotinib had a trend of less hypertension (50% vs. 67.4%, p = 0.0647), increase of creatinine (14.4% vs. 27.9%, p = 0.095), hypophosphatemia (13.3% vs. 27.9%, p = 0.085). Whereas, anlotinib had a trend of higher incidence of hypercholesterolemia (25.6% vs.11.6%, p = 0.073) than sunitinib. Conclusions: Anlotinib was shown to have similar efficacy to sunitinib with favorable safety profile in patients with metastatic RCC. Clinical trial information: NCT02072031.