Low dosage 177LuDOTATATE (177LuPRRT) re-treatment in GEP-NEN patients who relapse after 177LuPRRT

Objectives 177Lu Dotatate peptide receptor radionuclide therapy (177LuPRRT) has proven to be a valid therapy for gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). Generally, a disease control rate (DCR) is obtained in more than 75% of patients along with progression-free survival (PFS) lasting more than 2 years. As severe toxicity is rare, these patients may be candidates for re-treatment with 177LuPRRT at relapse. In a previous “second-line” protocol for GEP-NEN patients, we administered 18.5GBq 177LuPRRT in 5 cycles, obtaining an 82% DCR and median PFS of 22 months (95 % CI 16 - n.r). In the present study we investigated the outcome of 4 cycles of a lower dosage of 177LuDotatate (3.7 GBq) administered as “second-line PRRT”.

Methods 26 consecutive GEP NEN patients previously treated with 177LuPRRT at a dosage of 18.5/27.7 GBq in 5 cycles were prospectively re-treated with 177LuPRRT (14.8GBq in 4 cycles) after relapse. All patients had preserved kidney and hematological parameters and had had a PFS of at least 12 months after the first PRRT cycle. Toxicity, DCR and PFS were evaluated.

Results Six patients discontinued therapy after the first cycle and 2 after the second because of tumor progression. All the other patients received the intended treatment schedule. We registered G2 hematological toxicity in 3 patients; no kidney toxicity was reported. An overall DCR of 70% was observed. The median PFS was 9 months (95% CI 517 ).

Conclusions 177LuPRRT re-treatment can be considered a valid option for relapsed GEP NEN patients. However, whilst the 14.8GBq administered in 4 cycles did not induce substantial toxicity, DCR and PFS were lower than those of our previous study using 18.5 GBq in 5 cycles. Our results suggest that an activity of 14.8GBq 177Lu-PRRT in 4 cycles is suboptimal in advanced GEP NENs.