Dose escalation of an Evans blue-modified radiolabeled somatostatin analog Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors.

PURPOSE

To evaluate the safety and efficacy of Lu-DOTA-EB-TATE, a radiolabeled somatostatin analog modified by Evans blue, at escalating doses, was used to increase tumor retention in patients with progressive metastatic neuroendocrine tumors (NETs).

METHODS

Thirty-three patients with metastatic NETs were prospectively enrolled into four groups: group A (n = 6, 43 ± 12 years) administered approximately 3.7 GBq (100 mCi) Lu-DOTATATE as controls; group B (n = 7, 55 ± 7 years) administered approximately 1.11 GBq (30 mCi) Lu-DOTA-EB-TATE; group C (n = 6, 55 ± 10 years) administered approximately 1.85 GBq (50 mCi) Lu-DOTA-EB-TATE; group D (n = 14, 50 ± 10 years) administered approximately 3.7 GBq (100 mCi) Lu-DOTA-EB-TATE. Treatment-related adverse events were graded according to the CTCAE v.5.0. Ga-DOTATATE PET/CT were performed at baseline and 2-3 months after treatment for response evaluation.

RESULTS

Administration was well tolerated. No CTC 3/4 hematotoxicity, nephrotoxicity, or hepatotoxicity was observed during or after treatment in groups A-C. In group D, CTC-3 hematotoxicity was recorded in 2 patients with multicourse chemotherapy previously. After one-cycle treatment, the SUVmax decreased in group C (Δ% = - 17.4 ± 29.3%) and group D (Δ% = - 15.1 ± 39.1%), but greatly increased in group B (Δ% = 30.0 ± 68.0%) and mildly increased in group A (Δ% = 5.4 ± 45.9%). Referring to EORTC criteria, 16.7% (1/6), 0% (0/7), 50% (3/6), and 50% (7/14) were evaluated as partial response in groups A, B, C, and D, respectively. When selecting lesions with comparable baseline SUVmax ranging from 15 to 40, SUVmax showed no significant decrease in group B (Δ% = - 7.3 ± 24.5%) (P = 0.214), significant decrease in group C (Δ% = - 34.9 ± 12.4%) (P = 0.001), and in group D (Δ% = - 17.9 ± 19.7%) (P = 0.012) as compared with group A with increased SUVmax (Δ% = 8.4 ± 48.8%). SUVmax significantly decreased in the EBTATE groups (groups B-D combined) (Δ% = - 19.0 ± 21.5%) as compared with the TATE group (P = 0.045).

CONCLUSION

Lu-DOTA-EB-TATE is well tolerated and is more effective than Lu-DOTATATE. Both 1.85 GBq (50 mCi) and 3.7 GBq (100 mCi) doses appear to be more effective than 1.11 GBq (30 mCi) dose. Further investigation with more cycles of Lu-DOTA-EB-TATE treatment and longer follow-up is warranted.

TRIAL REGISTRATION

Treatment Using 177Lu-DOTA-EB-TATE in Patients with Advanced Neuroendocrine Tumors (NCT03478358). URL: https://register.clinicaltrials.gov/prs/app/action/ViewOrUnrelease?uid=U0001JRW&ts=13&sid=S0007RNX&cx=y3yqv4.