Jonathan Strosberg1, Oscar Leeuwenkamp2, Mohd Kashif Siddiqui3. 1. Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA. Electronic address: Jonathan.Strosberg@moffitt.org. 2. Advanced Accelerator Applications (AAA), a Novartis Company, Rue de la Tour de l'Ile 4, 1204 Geneva, Switzerland. Electronic address: Oscar.Leeuwenkamp@adacap.com. 3. Parexel, Access Consulting, Mohali, Punjab, India. Electronic address: Kashif.Siddiqui@parexel.com.
Abstract
BACKGROUND: This review and meta-analysis examined published evidence of peptide receptor radionuclide therapy (PRRT) re-treatment efficacy and safety in patients with advanced neuroendocrine tumors (NETs). METHODS: Embase, MEDLINE, MEDLINE In-Progress, and Cochrane CENTRAL were searched (database inception-present) to identify evidence of efficacy and safety of PRRT re-treatment in adults with NETs previously treated with 177Lu- and/or 90Y-PRRT. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) from time of re-treatment were assessed. Data were pooled using medians and variance for time-to-event outcomes and inverse-variance weighted proportions (Freeman-Tukey method) for binary outcomes. RESULTS: Of 567 studies screened, 13 reported re-treatment efficacy outcomes. In random-effects meta-analyses of 177Lu-PRRT re-treatment, median PFS (N = 7 studies [414patients]) was 12.52 months (95% CI 9.82-15.22) with moderate heterogeneity across studies (I2 = 50.5%), median OS (N = 2 [194 patients]) was 26.78 months (95% CI 18.73-34.83) with moderate-to-high heterogeneity (I2 = 57.5%), and DCR (N = 8 [347 patients]) was 71% (95% CI 66-75) with high heterogeneity (I2 = 81.5%). PFS was similar with either 177Lu-PRRT re-treatment alone or in combination with 90Y-PRRT. Grade 3/4 adverse events occurred in 5% (95% CI 2-8) of patients receiving 177Lu-PRRT re-treatment (N = 5 [271 patients]) with few grade 3/4 renal toxicities (0% [95% CI 0-1]). Pooled myelodysplastic syndrome and acute myeloid leukemia incidence was 0% (95%CI 0-2). CONCLUSION: Re-treatment with 177Lu-PRRT provided encouraging median PFS in patients with NETs with a safety profile similar to initial PRRT.
BACKGROUND: This review and meta-analysis examined published evidence of peptide receptor radionuclide therapy (PRRT) re-treatment efficacy and safety in patients with advanced neuroendocrine tumors (NETs). METHODS: Embase, MEDLINE, MEDLINE In-Progress, and Cochrane CENTRAL were searched (database inception-present) to identify evidence of efficacy and safety of PRRT re-treatment in adults with NETs previously treated with 177Lu- and/or 90Y-PRRT. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) from time of re-treatment were assessed. Data were pooled using medians and variance for time-to-event outcomes and inverse-variance weighted proportions (Freeman-Tukey method) for binary outcomes. RESULTS: Of 567 studies screened, 13 reported re-treatment efficacy outcomes. In random-effects meta-analyses of 177Lu-PRRT re-treatment, median PFS (N = 7 studies [414patients]) was 12.52 months (95% CI 9.82-15.22) with moderate heterogeneity across studies (I2 = 50.5%), median OS (N = 2 [194 patients]) was 26.78 months (95% CI 18.73-34.83) with moderate-to-high heterogeneity (I2 = 57.5%), and DCR (N = 8 [347 patients]) was 71% (95% CI 66-75) with high heterogeneity (I2 = 81.5%). PFS was similar with either 177Lu-PRRT re-treatment alone or in combination with 90Y-PRRT. Grade 3/4 adverse events occurred in 5% (95% CI 2-8) of patients receiving 177Lu-PRRT re-treatment (N = 5 [271 patients]) with few grade 3/4 renal toxicities (0% [95% CI 0-1]). Pooled myelodysplastic syndrome and acute myeloid leukemia incidence was 0% (95%CI 0-2). CONCLUSION: Re-treatment with 177Lu-PRRT provided encouraging median PFS in patients with NETs with a safety profile similar to initial PRRT.
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