Sorafenib 400 mg bid plus doxorubicin 60 mg/m(2) was well tolerated. The increased doxorubicin exposure with sorafenib 400 mg bid did not result in significantly increased toxicity; low patient numbers make the clinical significance of this unclear. These promising efficacy results justify further clinical investigation.

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9511 Background: There is no established systemic treatment for pts with MUM. The STREAM study evaluated the efficacy of the oral multikinase inhibitor S in chemonaïve pts with MUM with the primary endpoint progression-free survival (PFS). Methods: During the initial 56d run-in period all pts received oral S 400 mg bid with concomitant monitoring by magnetic resonance imaging including diffusion weighted imaging (DWI-MRI). Pts with partial remission (PR) on d56 according to RECIST 1.1 were further treated with open-label S and monitored, pts with progressive disease (PD) were taken off study, and pts with stable disease (SD) were randomly assigned to blinded S or placebo (P) and were further monitored every 8 wks and unblinded in case of PD. Pts on S were taken off study and pts on P were offered S with further monitoring. Results: Altogether, 118 (79.2%) of 149 pts entering the run-in period were evaluable for response on d56. Two pts had PR (1.7%), 78 pts had SD (66.1%) and 38 pts had PD (32.2%), respectively. Median PFS from randomization was significantly longer with S (5.5 mths) than P (1.9 mths, HR = 0.527, p = 0.0079). S was readministered to 23 pts with PD under P (59.0%) with a median PFS of 2.0 mths (range 1.2-15.7 mths). Overall survival (OS) was not different between the S group (median 14.8 mths, range 3.7-38.3 mths) and the P group (median 14.4, range 3.3-37.3 mths). During the entire study there were 43 NCI-CTCAE grade 3 and 9 grade 4 adverse events requiring dose reduction of S to 200 mg bid or treatment discontinuation, respectively. No pt died from toxicity. The evaluation of the apparent diffusion coefficient (ADC) ratio derived from DWI-MRI in 47 pts of the run-in period showed a significant difference between pts with SD and pts with PD (p < 0.05). Conclusions: The primary endpoint of STREAM was reached. S is clinically active and tolerable in first-line treatment of pts with MUM with an increase of median PFS from 1.9 mths for P to 5.5 mths for S (p = 0.0079). The median OS of 14.8 mths compares favorably with previous findings in pts with MUM. Besides morphological MRI features, ADC ratio may be used as an additional functional response criterion. Clinical trial information: NCT01377025.

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