Radiological and Clinical Efficacy of Intra-Arterial 90Y-DOTATATE in Patients with Unresectable, Progressive, Liver Dominant Neuroendocrine Neoplasms

Abstract

This study was performed to determine if intra-arterial (i.a.) administration of ⁹⁰Y DOTATATE can provide an effective and safe alternative to the accepted standard for i.v. of peptide receptor radionuclide therapy (PRRT) in liver-dominant metastases of gastrointestinal pancreatic neuroendocrine neoplasm (GEP-NEN). A single site, prospective, preliminary case series study included 39 patients with histologically proven liver-dominant NEN. PRRT in the form of 1.15GBq ⁹⁰Y DOTATATE was given selectively into the liver via radiological catheterization of the hepatic artery, up to four times. The endpoint was radiological response (RECIST). Secondary endpoints assessed clinical well-being post-treatment, progression-free survival (PFS), overall survival (OS), and toxicity. Partial response (PR) was noted in 13% of subjects six weeks post-therapy, increasing to 24% at six months and dropping to 13% at 36 months. Disease progression (DP) was not seen at six weeks, was 5% at six months, and 47% at 36 months. Clinical response based on PS seen in 74% of patients at six weeks, 69% at six months, and 39% at 36 months had PFS and OS, respectively, of 22.7 months and 38.2 months. There was no difference in OS/PFS between those with RECIST PR and SD. One patient had significant toxicity (3%). Use of i.a. PRRT appears to be safe and effective in treating patients with liver-dominant NEN. In addition, the best OS (51 vs. 22 months) was seen when i.a. was used as an upfront treatment of bulky GEP-NEN liver metastases and not after i.v. ⁹⁰Y DOTATATE. The use of i.a. ⁹⁰Y DOTATATE PRRT appears to be safe and effective in treating patients with liver-dominant NEN.

Keywords: 90Y-DOTATATE; OS; PFS; PRRT-intra-arterial (i.a.); neuroendocrine neoplasms; radiological and clinical response.

Figure 1

Study design, including main inclusion criteria, selection of two groups of patients, and endpoints.

Figure 2

The waterfall plot of ORR in selected time frame points of evaluation at six weeks, six months, 12 months, and 24 months in the group with initially i.a.PRRT (n = 23).

Figure 3

The waterfall plot of ORR in selected time frame points of evaluation at six weeks, six months, 12 months, and 24 months in the group with previous i.v. PRRT (n = 16).

Figure 4

OS and PFS in all patients during follow-up. Median OS 38.2 months (95% CI 34.0–71.2) and median PFS 24.1 months (95% CI 16.7–30.9). Data are presented for all patients who received at least two doses of PRRT during the study. The number of subjects remaining at risk below is 10% of cases in any group.

Figure 5

Comparison of OS in patients with previous i.v. PRRT and initially i.a. PRRT median 22.2 (CI 16.3–52.3) vs. 52.1 (CI 44.3–104.8) (p = 0.02 Cox Mantel Test). The number of subjects remaining at risk is below 10% of cases in any group.

Figure 6

Comparison of PFS in patients with previous i.v. PRRT at 12.3 months (95% CI 9.1–33.1) and initially i.a. PRRT at 28.4 months (95% CI 23.5–39.4) at six months of DCR. (p = 0.048 Cox–Mantel test). Disease control rate was defined as the proportion of patients with partial response (PR) or stable disease (SD), not patients with complete response (CR). The number of subjects remaining at risk was below 10% of cases in any group.

Figure 7

Comparison of PFS in patients with previous i.v. PRRT at 19.1 months (95% CI 9.2–35.6) and initially i.a. PRRT at 29.6 months (95% CI 27.7–43.1) at 12 months of DCR (p = 0.026 Cox–Mantel test). Disease control rate was defined as the proportion of patients with partial response (PR) or stable disease (SD), not patients with complete response (CR). The number of subjects remaining at risk was below 10% of cases in any group.