177Lu-DOTATATE peptide receptor radionuclide therapy versus Everolimus in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis

Objective Advanced pancreatic neuroendocrine tumors (pNETs) present a therapeutic challenge with targeted therapies like Everolimus and Lu-177-DOTATATE peptide receptor radionuclide therapy (PRRT) showing beneficial effects in various cohort studies and randomized trials. Currently there is a paucity of trials with head-to-head comparison between PRRT and Everolimus in advanced pNETs. This systematic review was conducted to compare the therapeutic efficacy and safety profile of Lu-177-DOTATATE and Everolimus in advanced pNETs. Methods The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Searches in Pubmed, Scopus and Embase using relevant keywords selected articles up to June 2019. Data on efficacy and safety were extracted from the individual articles. Random effects model was used for meta-analysis. Results Fifteen articles consisting of 697 patients reported on Lu-177-DOTATATE and 12 articles consisting of 946 patients reported on Everolimus. Overall, treatment with in Lu-177-DOTATATE had better objective response rate (47% vs. 12%, P< 0.001) and disease control rate (81% vs. 73%, P< 0.001) and longer progression-free survival (25.7 months vs. 14.7 months, P< 0.001) than with Everolimus. Lu-177-DOTATATE also had a better safety profile than Everolimus with fewer patients showing grade 3/4 hematological toxicity(5% vs. 11%, P= 0.02) and nephrotoxicity (1% vs. 2.5%, P= 0.34). Treatment-related adverse events caused discontinuation of therapy more frequently for Everolimus than for Lu-177-DOTATATE (59 out of 371 patients vs. 0 out of 128 patients). Conclusion From this meta-analysis, Lu-177-DOTATATE showed better therapeutic efficacy and safety profile compared to Everolimus in advanced pNETs. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.