Objective: To evaluate the efficacy, toxicity and survival of salvage peptide receptor radionuclide therapy (PRRT) with indigenous, direct-route ¹⁷⁷Lu-labelled-DOTATATE in metastatic Nueroendocrine tumor (NET) patients who showed an objective response or disease stabilization following initial course of ¹⁷⁷Lu-DOTATATE PRRT cycles and eventually developed progressive disease after a time-interval of more than 1 year; the variables influencing survival and response of salvage PRRT were also examined.

Methods: A total of 26 progressive metastatic NET patients who received salvage PRRT with indigenous ¹⁷⁷Lu-DOTATATE, were evaluated. Response was assessed under three broad categories as clinical symptomatic, biochemical and imaging (both molecular and morphological imaging). The Kaplan-Meier product-limit method was used to calculate progression-free survival (PFS) and overall survival (OS). Toxicity of salvage PRRT was evaluated by NCI-CTCAE v. 5.0 criteria (included complete blood counts, renal and liver function tests). Association between various variables and response and survival were analyzed using the χ² test.

Results: Out of the 26 patients, the complete follow-up data were not available for four patients, where only survival information was available. Thus, a total of 22 patients (median age: 55 years, range: 38-68 years, 12 men and 10 women) were included and analyzed retrospectively in study. The cumulative dose of initial course of PRRT (I-PRRT) with indigenous ¹⁷⁷Lu-DOTATATE ranged from 800 mCi (29.6 GBq) to 1231 mCi (45.54 GBq) per patient {mean administered cumulative dose of 964 mCi (35.66 GBq) per patient}, and the salvage PRRT with indigenous ¹⁷⁷Lu-DOTATATE comprised of a mean dose of 170 mCi (6.29GBq) per patient. The disease control rate of 68.1%, 77.3%, 63.6% and 63.6% were observed after salvage PRRT on clinical symptomatic, biochemical, molecular and morphological imaging response respectively. The median PFS after salvage PRRT was 17 months. The median OS was not attained after I-PRRT (OS-i) and salvage PRRT (OS-s). Estimated OS-i rate was 68% at 108 months and OS-s rate was 82% at 18 months. None of the patients developed Grade 3/4 hematotoxicity, nephrotoxicity and hepatotoxicity or AML/MDS after I-PRRT and salvage PRRT at median follow-up of 72 months and 12 months respectively. The highest level of toxicity was Grade 2 [seen as reversible anemia, thrombocytopenia and nephrotoxicity in 3 (13.5%), 1 (4.5%) and 2 patients (9%) respectively]. The significant p-value was not observed for any variable association.

Conclusion: With limited therapeutic options available for progressive NET after I-PRRT and in the absence of high-grade toxicity after ¹⁷⁷Lu-DOTATATE salvage PRRT, retreatment with PRRT may be considered as a relatively safe therapeutic option for these patients.

Advances in knowledge: This study examined salvage retreatment PRRT with indigenous ^"direct-route" ¹⁷⁷Lu-DOTATATE and registered its safety and survival benefits, indicating this could be an effective therapeutic option in this clinical setting.