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

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

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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Combined Modality Therapy
  • Coordination Complexes / administration & dosage
  • Coordination Complexes / adverse effects
  • Coordination Complexes / therapeutic use*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Neuroendocrine Tumors / diagnosis
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / radiotherapy*
  • Octreotide / administration & dosage
  • Octreotide / adverse effects
  • Octreotide / analogs & derivatives*
  • Octreotide / therapeutic use
  • Positron Emission Tomography Computed Tomography
  • Radiation Dosage
  • Radiometry
  • Radiopharmaceuticals / adverse effects
  • Radiopharmaceuticals / therapeutic use*
  • Receptors, Peptide / metabolism
  • Retreatment
  • Salvage Therapy
  • Treatment Outcome

Substances

  • 177Lu-DOTA-octreotate
  • Coordination Complexes
  • Radiopharmaceuticals
  • Receptors, Peptide
  • Octreotide