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. 2019 Aug 8;19(1):788.
doi: 10.1186/s12885-019-6000-y.

Salvage PRRT with 177Lu-DOTA-octreotate in extensively pretreated patients with metastatic neuroendocrine tumor (NET): dosimetry, toxicity, efficacy, and survival

S Rudisile  1 , A Gosewisch  1 , V Wenter  1 , M Unterrainer  1 , G Böning  1 , F J Gildehaus  1 , W P Fendler  1   2 , C J Auernhammer  3   4 , C Spitzweg  3   4 , P Bartenstein  1   4 , A Todica  1   4 , H Ilhan  5   6
Affiliations

Salvage PRRT with 177Lu-DOTA-octreotate in extensively pretreated patients with metastatic neuroendocrine tumor (NET): dosimetry, toxicity, efficacy, and survival

S Rudisile et al. BMC Cancer. .

Abstract

Background: NETTER-1 trial demonstrated high efficacy and low toxicity of four cycles of Peptide Receptor Radionuclide Therapy (PRRT) in patients with metastasized NET. The present study evaluates the outcome of further PRRT cycles in the so called salvage setting in patients after initial response to four therapy cycles and later progression.

Methods: Thirty five patients (pat.) (25 male, 10 female, 63 ± 9 years) with progressive, metastasized NET (23 small intestinal, 5 lung, 4 CUP, 1 rectal, 1 gastric and 1 paraganglioma) were included. All patients previously received 4 PRRT cycles with 177Lu-DOTATATE and showed initial response. SPECT based dosimetry was applied to determine kidney and tumor doses. Therapy response was evaluated using 68Ga-DOTATATE PET/CT (with high dose CT), CT alone or MRI (RECIST 1.1), toxicity was defined using CTCAE 5.0 criteria. 99mTc99-MAG3 scintigraphy was used to assess potential renal tubular damage. Progression free survival (PFS) and Overall survival (OS) analysis was performed with the Kaplan-Meier-method.

Results: The median PFS after initial PRRT was 33 months (95% CI: 30-36). The mean cumulative dose for including salvage PRRT was 44 GBq (range 33.5-47). One pat. (2.9%) showed grade 3 hematotoxicity. Kidney dosimetry revealed a mean cumulative kidney dose after a median of 6 PRRT cycles of 23.8 Gy. No grade 3 / 4 nephrotoxicity or relevant decrease in renal function was observed. Follow-up imaging was available in 32 patients after salvage therapy. Best response according to RECIST 1.1. was PR in one patient (3.1%), SD in 26 patients (81.3%) and PD in 5 patients (15.6%). PFS after salvage therapy was 6 months (95% CI: 0-16; 8 patients censored). Mean OS after initial PRRT was 105 months (95% CI: 92-119) and 51 months (95% CI: 41-61) after start of salvage therapy. Median OS was not reached within a follow-up of 71 months after initial PRRT and 25 months after start of salvage PRRT, respectively.

Conclusions: Salvage therapy with 177Lu-DOTATATE is safe and effective even in patients with extensive previous multimodal therapies during disease progression and represents a feasible and valuable therapy option for progressive NET.

Keywords: Dosimetry; NET; PRRT; SPECT; Salvage therapy; Survival.

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Conflict of interest statement

HI is an advisory board member of Bayer, received research funding from Novartis and speaker honoraria from Bayer and Ipsen. CA has received research contracts from Ipsen, Novartis, and ITM Solucin, lecture honorarium from Ipsen, Novartis, and Falk Foundation, and advisory board honorarium from Novartis. CS has received research grants from Novartis, lecture honoraria from Ipsen and Novartis, and advisory board honoraria from Ipsen, Novartis, and Pfizer. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Cumulative absorbed Dose for kidneys and tumor lesions. Boxplot-Analysis of the cumulative dose for kidneys and tumor lesions. A significantly higher cumulative dose was found for liver metastases and lymph node metastases compared to bone and peritoneal tumor lesions each
Fig. 2
Fig. 2
Kaplan-Meier-Survival analysis for PFS and OS after 1st and salvage PRRT. Kaplan-Meier-Survival Analysis for PFS and OS. Every patient showed initial response to four cycles of 177Lu-DOTATATE and later progression prior to salvage PRRT. Median PFS after the start of PRRT was 33 months (a). The median PFS after start of salvage therapy was 6 months (b) median follow-up time: 25 months; 3 patients lost to follow-up, 8 patients censored). Median OS was not reached during a median follow-up of 71 months from start of 1st PRRT cycle (c) and 25 months from the start of salvage PRRT (d)
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