177Lu-PRRT in advanced gastrointestinal neuroendocrine tumors: 10-year follow-up of the IRST phase II prospective study

Purpose: In March 2014, we reported the activity and safety of 177Lu-DOTA-octreotate peptide receptor radionuclide therapy (Lu-PRRT) at two different dosages (18.5 GBq and 27.5 GBq in 5 cycles) in patients with progressive metastatic gastrointestinal neuroendocrine tumors (GI-NETs). Disease control rate (DCR) and toxicity were addressed. Herein, we report the late toxicity, progression-free survival (PFS), and overall survival (OS) in the same cohort after a 10-year follow-up. Methods: We conducted an open-label, disease-oriented prospective phase II trial. From March 2008 to June 2011, 43 patients received 3.7 GBq or 5.5 GBq of Lu-PRRT every 6 to 8 weeks, each cycle repeated 5 times. All patients showed 68Gallium-DOTA-peptide PET/Octreoscan® positivity (score 3–4 Rotterdam scale) in known lesions. Tumor burden was estimated radiologically. Time-to-event data (PFS and OS) were described using Kaplan-Meier curves and compared with the log-rank test. Results: Forty-three patients (28 males and 15 females) were evaluable and were monitored for a median period of 118 months (range 12.6–139.6). Median PFS in patients receiving 18.5 GBq was 59.8 months (95% confidence interval [95% CI] 14.3–79.6), identical to that of patients treated with 27.5 GBq (59.8 months, 95% CI 23.4–82.0). Median OS was 71.0 months (95% CI 46.1–107.3) in the group who received 18.5 GBq and 97.6 months (95% CI 64.3-not reached) in the group treated with 27.5 GBq (P = 0.22). Patients with progression limited to lymph nodes showed significantly longer median PFS and OS than those with hepatic lesions (P = 0.02 for PFS and P = 0.04 for OS). Age over 65 years at the time of PRRT was also significant for OS. Of note, no late hematological or renal toxicity was observed in either group. Conclusions: The long-term follow-up of the IRST phase II study shows that Lu-PRRT is a safe and effective therapy for patients with advanced GI-NET, the most important prognostic factor being tumor burden, hepatic lesions, and age. We believe that Lu-PRRT should be offered to patients with early-stage disease.