Table 1

Phase II trials of sorafenib in DTC

Trial

Efficacy Results

Grade ≥ 3 AEs in ≥ 5%

of Patients

Other


Single-arm trial

(N = 55 total;

n = 47 DTC) [10-12]

mPFS = 84 weeks*

SD = 53.3%

PR = 23.3%

DCR = 76.6%

OS = 140 weeks

Hypertension (13%), hand-foot syndrome (10%), rash (10%), weight loss (10%), diarrhea (7%), elevated LFTs (7%)

• Dose reduction (due to AEs) was required in 47% of patients (initial analysis)

• Median duration of treatment at initial analysis (30 of 55 patients accrued) = 27 weeks

• BRAF genotyping (n = 16): mPFS = 84+ weeks in DTC patients with BRAFV600E, compared with 54 weeks in those with BRAFwt (P = 0.028)

Single-arm component (chemotherapy-naive patients with DTC) of two-arm trial (N = 56 total; n = 41 DTC) [13]

mPFS = 65 weeks*

SD = 57%*

PR = 15%*

DCR = 72%*

Fatigue, HSFR (11% each); weight loss, skin rash, hypertension, diarrhea, stomatitis, tongue/tooth pain, abdominal/rectal pain, proximal myopathy, back pain, general pain, hand/foot pain, arthralgia, colon perforation (5% each)

• Dose reduction (due to AEs) was required in 52% of patients

Single-arm trial

(N = 26 total;

n = 14 DTC) [14,15]

mPFS not reported

SD = 82%

PR = 18%

DCR = 100%

Hand-foot syndrome (19%), other skin toxicity (6%),

hypertension (6%), infection (8%)

• Dose reduction (due to AEs) was required in 62% of patients

• Five drug-related serious AEs were reported:

2 hospitalizations for non-neutropenic fever/infection, 1 for hypocalcemia, and 2 for fever/rash

Single-arm trial

(N = 31; all DTC) [16]

mPFS = 58 weeks

SD = 34%

PR = 25%

DCR = 59%

HFSR (22%), hypertension (16%), weight loss (9%)

• Dose reduction (due to AEs) was required in 56% of patients


*DTC cohort

Total study sample

One patient developed grade 3/4 LFT abnormalities at 8 weeks and died of liver failure 12 weeks later

DTC = differentiated thyroid cancer; mPFS = median progression-free survival; SD = stable disease; PR = partial response;

DCR = disease control rate; LFTs = liver function tests; HFSR = hand-foot skin reaction; AE = adverse event

Brose et al. BMC Cancer 2011 11:349   doi:10.1186/1471-2407-11-349

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