A Phase Ii Trial Of Sorafenib (So) In Advanced Chordoma Patients (Pt)

10520 Background: To report in a hypothesis-generating phase II study the activity and safety of SO in advanced chordomas. Methods: Pts received SO 800 mg/d until progression, intolerance or up to 9 months (mo) and intolerance. The primary endpoint was progression-free survival according to RECIST 1.1. Secondary end-points were RR, OS and toxicity. Results: From 07/2011 to 01/2014, 27 pts were enrolled (median age 64, range 30-86), including 17 men and 10 women. The primary tumor locations were sacrum (21, 77.7%), rachis (4, 14.8%) and clivus (3, 11.1%). Metastasis was present in 14 pts (58.3%). Twenty-six pts (96.3%) had received prior treatment, including surgery (18, 66.7%), radiotherapy (18, 66.7%) and prior systemic therapies (MTT; 12, 44.4%; median number of lines 1, range 1-3). The duration of SO treatment was 4.9 months (range, 0.5-10.1). The median relative dose-intensity was 1 (range, 0.43-1). Because of toxicity, treatment was temporarily discontinued for 11 pts (40.7%) and dose-reduction was necessary in 10 cases (37.0%) A 6 mo, we have observed 1 delayed RECIST-based partial response confirmed at 9 mo. The median follow-up was 8.7 mo (1.2-31.0 mo). The 12 month-PFS rate was 57.4% (95CI 34.7-74.7) in the whole population, and 63.6% (32.7-83.3) and 47.1% (15.2-74.1) in pts naïve to and those previously treated by MTT, respectively. The 12 month-OS rate was 86.5% (55.8-96.5). Three (11.1%) and 14 (51.8%) pts experienced grade (Gr) 4 and Gr 3 toxicities. The Gr 4 toxicities were thyrotoxicosis (1 case), skin toxicity (1 case) and arterial hypertension (1 case). The most common Gr 3 toxicities were arterial hypertension (5), skin toxicity (5) and diarrhea (5, 18.5%). One keratoacanthoma occurred during follow-up. Conclusions: This trial showed a promising activity of SO in advanced chordoma. Further clinical explorations (e.g. randomization trial with discontinuation design) are warranted. Clinical trial information: 2009-017020-59.