Two prospective, randomized phase 3 clinical trials were conducted in patients with well-differentiated thyroid cancer to compare 131I whole body scans obtained after THYROGEN injection to 131I whole body scans after thyroid hormone withdrawal. A cross-over, non-blinded design was used in both trials. Oral radioiodine was given 24 hours after the second injection of THYROGEN, and scanning was done 48 hours after the radioiodine administration. Each patient was scanned first following THYROGEN and then scanned after thyroid hormone withdrawal. In both studies, the primary endpoint was the rate of concordant scans (scan findings in agreement in a given patient using each preparation method).

Study 1 (n=127) compared the diagnostic scanning following a THYROGEN regimen of 0.9 mg IM daily on two consecutive days to thyroid hormone withdrawal. In addition to body scans, Study 2 (n=229) also compared thyroglobulin (Tg) levels obtained after THYROGEN to those at baseline and to those after thyroid hormone withdrawal. All Tg testing was performed in a central laboratory using a radioimmunoassay (RIA) with a functional sensitivity of 2.5 ng/mL. Patients who were included in the Tg analysis were those who had undergone total or near-total thyroidectomy with or without 131I ablation, had <1% uptake in the thyroid bed on a scan after thyroid hormone withdrawal, and did not have detectable anti-Tg antibodies. The maximum THYROGEN Tg value was obtained 72 hours after the final THYROGEN injection, and this value was used in the analysis.

Diagnostic Radioiodine Whole Body Scan Results

Study 1 enrolled 127 patients, 71% were female and 29% male, and mean age was 44 years. The study included the following forms of differentiated thyroid cancer: papillary cancer (88%), follicular cancer (9%), and Hurthle cell (2%). Study results are displayed in Table 2.

In Study 2, patients with differentiated thyroid cancer who had been thyroidectomized (n=229) were randomized into one of two THYROGEN treatment regimens: THYROGEN 0.9 mg IM daily on two consecutive days (n=117), and THYROGEN 0.9 mg IM daily on days 1, 4 and 7 (n=112). Each patient was scanned first using THYROGEN, then scanned using thyroid hormone withdrawal. The group receiving the THYROGEN 0.9 mg IM × 2 regimen was 63% female/27% male, had a mean age of 44 years, and generally had low-stage papillary or follicular cancer (AJCC/TNM Stage I 61%, Stage II 19%, Stage III 14%, Stage IV 5%). The group receiving the THYROGEN 0.9 mg IM × 3 regimen was 66% female/34% male, had a mean age of 50 years, and generally had low-stage papillary or follicular cancer (AJCC/TNM Stage I 50%, Stage II 20%, Stage III 20%, Stage IV 9%). The amount of radioiodine used for scanning was 4 mCi ± 10%, and scanning times were lengthened in some patients to capture adequate images (30 minute scans, or 140,000 counts). Scan pairs were assessed by blinded readers. Study results are presented in Table 2.

Across the two clinical studies, and scoring all false positives in favor of thyroid hormone withdrawal, the majority of positive scans using THYROGEN and thyroid hormone withdrawal were concordant. The THYROGEN scan failed to detect remnant and/or cancer localized to the thyroid bed in 17% (14/83) of patients in whom it was detected by a scan after thyroid hormone withdrawal. In addition, the THYROGEN scan failed to detect metastatic disease in 29% (7/24) of patients in whom it was detected by a scan after thyroid hormone withdrawal.

Thyroglobulin (Tg) Results

THYROGEN Tg testing alone and in combination with diagnostic whole body scanning: comparison with results after thyroid hormone withdrawal

In anti-Tg antibody negative patients with a thyroid remnant or cancer (as defined by a withdrawal Tg ≥2.5 ng/mL or a positive scan [after thyroid hormone withdrawal or after radioiodine therapy]), the THYROGEN Tg was positive (≥2.5 ng/mL) in 69% (40/58) of patients after 2 doses of THYROGEN.

In these same patients, adding the whole body scan increased the detection rate of thyroid remnant or cancer to 84% (49/58) of patients after 2 doses of THYROGEN.

Among patients with metastatic disease confirmed by a post-treatment scan or by lymph node biopsy (35 patients), THYROGEN Tg was positive (≥2.5 ng/mL) in all 35 patients, while Tg on thyroid hormone suppressive therapy was positive (≥2.5 ng/mL) in 79% of these patients.

As with thyroid hormone withdrawal, the intra-patient reproducibility of THYROGEN testing with regard to both Tg stimulation and radioiodine imaging has not been studied.

Hypothyroid Signs and Symptoms

THYROGEN administration was not associated with the signs and symptoms of hypothyroidism that accompanied thyroid hormone withdrawal as measured by the Billewicz scale. Statistically significant worsening in all signs and symptoms were observed during the hypothyroid phase (p<0.01) (Figure 1).

Figure 1: Hypothyroid Symptom Assessment Billewicz Scale Diagnostic Indication 0.9 mg THYROGEN q 24 hours × 2 doses vs Thyroid Hormone Withdrawal Phase