Long-term outcomes of submaximal activities of peptide receptor radionuclide therapy with 177Lu-DOTATATE in neuroendocrine tumour patients

Rationale: In literature, up to 45% of the neuroendocrine tumour (NET) patients who are treated with peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE do not receive the intended cumulative activity of 29.6 GBq (800 mCi). The aim of this study was to analyse the efficacy of submaximal activities of PRRT in patients who discontinued for disease-unrelated reasons. Methods: Retrospective inclusion of well-differentiated and advanced NET patients who underwent PRRT from 2000 until 2019 and did not receive 29.6 GBq ¹⁷⁷Lu-DOTATATE. For comparison, we selected control NET patients who received the intended cumulative activity of 29.6 GBq ¹⁷⁷Lu-DOTATATE between 2000-2012. Primary outcomes were progression-free survival (PFS) and tumour response, and the secondary outcome was overall survival (OS). Results: In total 243 patients received 3.7-27.8 GBq. In 130 patients the submaximal activity was disease-unrelated (e.g. bone marrow and renal toxicity in 48% and maximal renal absorbed dose in 23%) and they were included. Patients receiving a reduced activity had more bone metastases, a lower BMI and albumin level, a higher alkaline phosphatase, and less grade 1 tumours than the 350 patients included in the control group. The disease control rate in the reduced activity group was 85% compared to 93% for the control group (P = 0.011). The median PFS (95%CI) was 23 (21-26) months for the reduced activity group and 31 (27-35) months for the control group (P = 0.001), and the median OS was 34 (28-40) months and 60 (53-67) months, respectively (P<0.0001). With adjustment for relevant confounders in the multivariable Cox regression analyses, cumulative activity was an independent predictor of both PFS and OS. Conclusion: In NET patients treated with a cumulative activity less than 29.6 GBq ¹⁷⁷Lu-DOTATATE, PRRT was less efficacious in terms of tumour response and survival compared to patients who received 29.6 GBq.