1. Abstract #11065
Efficacy of sorafenib in patients with desmoid-type fibromatosis Rodrigo Munhoz1, Robert A. Lefkowitz2, Deborah Kuk2, Mark A. Dickson2,3, Sandra P. D'Angelo2,3, Mary Louise Keohan2,3, Ping Chi2, Aimee M. Crago2,3, Robert G. Maki4, Gary K. Schwartz5, Li-Xuan Qin2, William D. Tap2,3, Mrinal M. Gounder2,3 Affiliations: 1. Hospital Sírio Libanês. São Paulo, Brazil; 2. Memorial Sloan Kettering Cancer Center, New York, NY; 3. Weill Cornell Medical College. New York, NY; 4. Icahn School of Medicine at Mount Sinai, New York, NY; 5. Columbia University Medical Center-New York Presbyterian Hospital. New York, NY
SO was the first systemic treatment in 49 pts (62%), most frequently at 400mg QD (n = 59; 75%). The median treatment duration was 13.6 months (mo). Dose modifications were required in 47 cases (59%) (Table 2).
Desmoid tumors (DT) are rare fibroblastic neoplasms characterized by a variable course and loco-regional aggressiveness.1,2
Observation, surgery, radiation and systemic agents are known therapies with variable outcomes.3
Although the optimal treatment strategy is yet to be determined, we previously reported on the efficacy of sorafenib (SO).4
 Here we review a larger cohort with long-term follow up (FU).  
Background
Figure 1. PFS and change in tumor size from baseline
RECIST
WHO
PFS A B C
Table 2. Treatment details
Reason for sorafenib discontinuation
Maximum benefit
Toxicity
POD
Other
Ongoing treatment
Lost follow up
30 (38%)
16 (20%)
10 (13%)
5 (6%)
13 (16%)
Subsequent systemic treatments No
Yes
Unknown
48 (61%)
20 (25%)
Subsequent loco-regional procedures
11 (14%)
Characteristic
Number (%)
Setting of sorafenib 
First line
POD on prior therapy
Max on prior therapy
Intol to prior therapy
Other
49 (62%)
24 (30%)
4 (5%)
1 (1%)
1(1%)
Initial dose 
200mg daily
400mg daily
>400mg daily
16 (20%)
59 (75%)
3 (4%)
Dose modifications 
Yes No
LFU
47 (59%)
30 (38%)
2 (2.5%)
Patients (pts) with progressive or symptomatic DT treated with SO at Memorial Sloan Kettering Cancer Center were retrospectively identified; diagnosis was confirmed centrally.
Patients enrolled in clinical trials investigating SO were excluded
Baseline/treatment characteristics were analyzed using descriptive statistics.
Responses were determined retrospectively by a reference radiologist according to RECIST v1.1 (unidimensional) and World Health Organization (WHO) criteria (bidimensional).
Kaplan-Meier curves were estimated for survival and variables correlated with treatment outcomes were investigated.  
Methods
Figure 1. PFS curve (A) and and change in tumor size from baseline using unidimensional measurements - RECIST criteria (B) and bidimensional measurements - WHO criteria (C)
PFS was not affected by site (p = 0.79), age (p = 0.72) or association with Familial Adenomatous Polyposis syndrome (FAP) (p = 0.51). 
Using cutpoint analysis, we identified a new cut-off of -5% change in tumor size using unidimensional measurements (RECIST) that correlated with disease control (median time to tumor progression from best scan of 37.1 mo for pts with ≤ -5% reduction versus 18.7 mo for pts with variations ≥ -5%; p=0.49).
POD – progression of disease / Max - maximum benefit/Intol – intolerance/LFU – loss of follow up
Conclusions
Results
After a median follow up (FU) of 31.2 mo, only 2 deaths occurred.
Among 51 pts who discontinued SO for reasons other than progressive disease, 25/51 pts (49%) had durable disease control (median FU: 29.1 mo).
Sixty-two pts were assessable for response; objective RR were 17.7% (RECIST) and 25.8% (WHO criteria) (Table 3 and Figure 1).
SO resulted in objective responses in pts with DT, with durable disease control and prolonged PFS;
Sustained stabilization was seen even after treatment interruption;
Activity was similar in both sporadic and FAP-associated DT;
Objective responses were better characterized using WHO criteria;
Minor tumor reductions may correlate with prolonged disease control, and the cut-off of -5% variation in tumor size needs to be explored in future studies.
We treated 79 pts with DT with SO between 2006 and January/2015; patients´ and disease characteristics are summarized in Table 1.
Table 1. Demographics and disease characteristics
Characteristic
Number (%)
Number of Patients
79 (100%)
Age- years
Median (range)
15-25
26-45
46-65
>65
37 (17-81)
17 (22%)
36 (46%)
23 (29%)
3 (4%)
Sex
Female
Male
53 (67%)
26 (33%)
Primary site
Extremities
Intra-abdominal
Chest wall
Abdominal wall
Other*
22 (28%)
19 (24%)
15 (19%)
13(16%)
10 (13%)
Characteristic
Number (%)
Size – primary tumor
≤5cm
5.1-10cm
>10cm
Not specified
20 (25%)
35 (44%)
18 (23%)
6 (8%)
Prior surgery R0 R1 R2 No
12 (15%)
9 (11%)
38 (48%)
Prior RT
Yes
72 (91%)
7 (9%)
Number of prior systemic therapies ≥2 1
21 (27%)
49 (62%)
Table 3. Treatment outcomes
Treatment outcomes for the entire cohort (n=79)
Median follow up
31.2 months
Median treatment duration
13.6 months
Median PFS*
Not reached (27 events)
Response to treatment (Among 62 evaluable patients)
Response
RECIST
WHO
Number % CR PR 11
17.7% 16
25.8% SD 51
82.3% 45
72.6%
POD 1
1.6%
Total (evaluable) 62
Fletcher CDM UK, Mertens F. Pathology and genetics of tumors of soft tissue and bone. Lyon, France: IARC Press; 2002.
Lewis JJ, Boland PJ, Leung DH et al. The enigma of desmoid tumors. Ann Surg 1999;229:866–72; discussion 872–3.
Kasper B, Baumgarten C, Bonvalot S et al. Management of sporadic desmoid-type fibromatosis: A European consensus approach based on patients‘ and professionals‘ expertise - A Sarcoma Patient EuroNet and European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group initiative. Eur J Cancer 2015; 52:
Gounder MM, Lefkowitz RA, Keohan ML et al. Activity of Sorafenib against desmoid tumor/deep fibromatosis. Clin Cancer Res. 2011 Jun 15;17(12):
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References
Table 3. PFS – progression-free survival / CR – complete response/PR – partial response/SD – stable disease/POD – progression of disease / * - for the entire cohort
History of FAP 
Yes
10 (13%)