“Rechallenge” peptide receptor radionuclide therapy (PRRT) may be less efficient than initial PRRT while safety profile is comparable

Introduction: For patients with gastrointestinal neuroendocrine tumours (GI-NETs), peptide receptor radionuclide therapy (PRRT) can be performed as a re-challenge (re-PRRT) after initial PRRT (i-PRRT). We compared efficacy and adverse events between re- vs. i-PRRT, along with possible prognosticators for outcome.

Methods: For 19 patients with GI-NET, Kaplan-Meier analysis was used to assess progression-free survival (PFS) after i- and re-PRRT. The Wilcoxon test was used to compare baseline laboratory values for leukocytes, hemoglobin, platelets, C-reactive protein, lactate dehydrogenase, creatinine, glomerular filtration rate, bilirubin, gamma-GT (GGT), alanine aminotransferase and alkaline phosphatase between i-PRRT and re-PRRT. At baseline and upon follow-up, we determined SSTR-directed PET metrics (SUV_mean, SUV_max and SSTR-positive tumor volume (SSTR-TV) as well as their changes. A univariable Cox regression analysis was performed to determine the prognostic value for PFS. Adverse events were classified according to CTCAE 5.

Results: The median interval between i-PRRT (median 4 [1-8] cycles, median activity 29.64 [8.1-60.8] GBq) and re-PRRT (median 2 [1-4] cycles, median activity 15.3 [7.7-30.0] GBq) was 38 (15-76) months. The median PFS after i-PRRT was 34 months and after re-PRRT 15 months (progression in 9/19 patients). In the interval between PRRT, all patients received somatotstatin analogs, 2/19 received surgery, 4/19 locoregional interventions, 2/19 radiotherapy, 2/19 immunotherapy, 1/19 chemotherapy and 1/19 tyrosine kinase inhibitor. Only median hemoglobin (11.9 vs. 13.1; p<0.01) and glomerular filtration rate (72 vs. 85; p<0.01) were significantly lower at beginning of re-PRRT. No significant differences were found in SSTR-TV (93.6 vs. 189.7 ml; p=0.33) and SUV_max (32.0 vs. 36.1; p=0.1) between i-PRRT and re-PRRT, while SUV_mean (8.6 vs. 9.9; p=0.05) trended to be lower in the initial PRRT. In the univariable Cox regression performed with laboratory values and the different PET parameters, only a higher SUV_mean was significantly associated with shorter PFS in the i-PRRT (HR 1.5 95%CI 1.2-2.0, p=0.003). However, this association was not seen in re-PRRT (HR 0.9 95%CI 0.7-1.2, p=0.5). Among patients with available PET scans (i-PRRT, 18; re-PRRT, 13), 10/18 (56%) showed a reduction in SSTR-TV after i-PRRT, but only 4/13 (31%) after re-PRRT. Among those 10 individuals with SSTR-TV reduction after i-PRRT, only 2/10 showed a TV decrease upon re-PRRT (one, no change; three, increase in SSTR-TV; four, no restaging available after re-PRRT). However, two patients with no SSTR-TV reduction after i-PRRT had SSTR-TV reduction upon re-PRRT. No ≥ CTCAE 3 occurred in the re-PRRT group, but grade 3 leukopenia after i-PRRT.

Conclusions: Rechallenge PRRT in patients with GI-NET demonstrates comparable low toxicity to i-PRRT, while it may be less efficient.