Radiosensitizing Favors Response to Peptide Receptor Radionuclide Therapy in Patients With Highly Proliferative Neuroendocrine Malignancies

Abstract

Aim/Introduction Peptide receptor radionuclide therapy (PRRT) represents a cornerstone of treatment regimens for patients with low proliferative neuroendocrine tumors (NETs). However, in patients experiencing somatostatin receptor–positive NET with higher proliferation rates, a value and potential therapeutic benefit of PRRT as part of multimodal treatment approaches and potentially with addition of radiosensitizing agents has not yet been established. Patients and Methods In this study, 20 patients with histologically confirmed gastroenteropancreatic (GEP) NET with proliferation rates (Ki67) between 15% and 55% were treated either with PRRT only (n = 10) or with a combination therapy (n = 10) comprising PRRT and capecitabine/temozolomide (CAP/TEM) for at least 2 consecutive cycles. Results Disease control rate in patients treated with PRRT alone was 60% (40% stable disease and 20% partial response). Strikingly, in patients treated with PRRT in combination with radiosensitization (CAP/TEM), the disease control rate was 90% (20% stable disease and 70% partial response). The median progression-free survival in the PRRT only group was 12 months, whereas the median progression-free survival in the PRRT + CAP/TEM group was 26 months and has not been yet reached for all patients in the group during the observation period. The median disease-specific survival for patients with PRRT alone was 51 months, whereas this end point was not yet reached in the PRRT + CAP/TEM group. Moreover, the PRRT + CAP/TEM group showed a significantly higher reduction of SSTR-PET–based metabolic tumor volume and chromogranin A levels compared with the PRRT only group. Importantly, adverse events of all grades did not differ between both groups. Conclusions PRRT + CAP/TEM represents a highly promising and well-tolerated therapeutic regimen for patients experiencing somatostatin receptor–positive NET with higher (Ki67 ≥ 15%) proliferation rate. Prospective randomized clinical trials are warranted.

Neuroendocrine Neoplasia: From Pathophysiology to Novel Therapeutic Approaches

“…A recent pilot study on somatostatin receptor-positive GEP NENs having a Ki67 proliferation index between 15% and 55%, studied the effects of PRRT, and the approach was offered either as a single-line therapy or as a combination treatment with capecitabine/temozolomide (with at least two consecutive cycles). The disease control rate was 60% compared to 90%; the median progression-free survival rate was higher in a statistically significant manner for the combined treatment (12 months compared to 26 months), hence suggesting that the multimodal sequence is more efficient than the single-line management [40].…”

“…Generally, we identified four modern trends in approaching PRRT for NENs: (A) the integration of multi-layered management in order to find out which is the best combination/synergistic therapy use with PRRT; (B) the usefulness of PRRT for subjects diagnosed with high-grade NENs who are not traditional candidates for PRRT; (C) the hypothesis of NENs inducing a shift to a more aggressive tumour than before the application of PRRT; and (D) the rising interest in and value of alpha particle PRRT compared with beta-emitting PRRT for NEN patients [1,2,[39][40][41][42][43][44].…”