TABLE 1.
Summary of key prospective studies of tyrosine kinase inhibitors in patients with desmoid tumors
| Study | Phase | Design | No. | Patients | ORR, % | DCR, % | Other | Safety |
|---|---|---|---|---|---|---|---|---|
| Imatinib | ||||||||
| CSTIB2225 (Heinrich 2006 74 ) | 2 | OL, single‐arm | 19 | Aged ≥17 years; any line; 63% ABD | 16 | 84 | 1‐year DCR, 37% | Dose reductions (from 400 mg BID) required for most patients due to Grade ≥ 3 toxicities |
| SARC (Chugh 2010 75 ) | 2 | OL, single‐arm | 51 | Aged ≥10 years; not amenable to surgery; any line; 16% ABD; 16% FAP | 6 | 84 | 1‐year PFS, 66% | Grade 3–4 AEs: neutropenia (10%), rash (10%), fatigue (8%); dose reductions in 39% |
| FNCLCC/FSG (Penel 2011 76 ) | 2 | OL, single‐arm | 40 | Aged ≥18 years; any line; progressive DT not amenable to RT or surgery; 45% ABD; 14% FAP | 11 | 91 | 1‐year PFS, 67%; 2‐year PFS, 55%; 2‐year OS, 95% | Grade 3 AEs: rash (10%), abdominal pain (10%), vomiting (8%); four discontinuations (10%) due to AEs |
| NCT01137916 (Kasper 2017 77 ) | 2 | OL, single‐arm | 38 | Aged ≥18 years; any line; progressive DT (last 6 months) not amenable to RT or surgery; 18% ABD; 3% FAP | 19 | NS | 6‐month PAR, 65%; mDOR, 413 days | Grade 4 AEs, 3%; Grade 3 AEs, 11%, including neutropenia, leucopenia, nausea/vomiting, gastritis, rash, and contracture |
| Sunitinib | ||||||||
| Jo et al. (Jo 2014 78 ) | 2 | OL, single‐arm | 19 | Aged ≥18 years; not amenable to curative surgery; 63% ABD; 53% FAP | 26 | 68 | mDOR, 8.2 months; 2‐year PFS, 75%; 2‐year OS, 94% | Grade 4 AEs: neutropenia (5%); most common Grade 3 AE: neutropenia (26%); most common any‐grade AE: thrombocytopenia (67%; all Grade 1–2) |
| Miano et al. (Miano 2019 79 ) | 2 | OL RCT | 22 (SU) | Progressive, symptomatic, or recurrent DT | 75 | 100 | 2‐year PFS, 81% | Most common AEs: Grade 1–2 hypothyroidism (73%), fatigue (67%), hypertension (55%), diarrhea (51%) |
| 10 (TM) | 0 | NS | 2‐year PFS, 36% | NS | ||||
| Sorafenib | ||||||||
| NCT02066181 (Gounder 2018 21 )a | 3 | DB RCT | 49 (SOR) | Aged ≥18 years; progression ≥10% in 6 months; inoperable or requiring extensive surgery, or symptomatic; any line | 33 | NS | 1‐year PFS, 89%; 2‐year PFS, 81% | Grade 3–4 AEs: Papulopustular rash (12%), hypertension (8%); most common AEs: fatigue (73%), hand‐foot syndrome (71%); withdrawals due to AEs, 20% |
| 36 (PBO) | 20 | NS | 1‐year PFS, 46%; 2‐year PFS, 36% | Grade 3–4 AEs: abdominal pain (11%), vomiting (6%); most common AEs: fatigue (64%), nausea (42%); withdrawals due to AEs, 0% | ||||
| Pazopanib | ||||||||
| NCT01876082 (DESMOPAZ; Toulmonde 2019 73 )b | 2 | OL RCT | 48 (PAZ) | Aged ≥18 years; progressive disease; any line; FAP, 16% | 37 | 96 | 1‐year PFS, 86%; 2‐year PFS, 67% | Grade 3–4 AEs: hypertension (21%), diarrhea (15%); most common AEs: fatigue (81%), diarrhea (80%); withdrawals due to AEs, 8% |
| 22 (MV) | 25 | 75 | 1‐year PFS, 79%; 2‐year PFS, 79% | Grade 3–4 AEs: neutropenia (46%), ALAT or ASAT increase (18%); most common AEs: nausea and vomiting (73%), fatigue (69%); withdrawals due to AEs, 23% |
Abbreviations: ABD, abdominal; AE, adverse event; ALAT, alanine aminotransferase; ASAT, aspartate aminotransferase; BID, twice daily; DB, double‐blind; DCR, disease control rate; FAP, familial adenomatous polyposis; FNCLCC/FSG, Fédération Nationale des Centres de Lutte Contre Le Cancer/French Sarcoma Group; mDOR, median duration of response; MV, methotrexate and vinblastine; NCT, ClinicalTrials.gov identification number; NR, not reached; NS, not specified; OL, open‐label; OS, overall survival; PAR, progression arrest rate; PAZ, pazopanib; PBO, placebo; PC, placebo‐controlled; PFS, progression‐free survival; RCT, randomized controlled trial; RT, radiotherapy; SARC, Sarcoma Alliance for Research through Collaboration; SOR, sorafenib; SU, sunitinib; TM, tamoxifen and meloxicam.
Randomized, double‐blind, placebo‐controlled trial.
Noncomparative randomized, open‐label trial.