Peptide receptor chemoradionuclide therapy for neuroendocrine neoplasms: A systematic review

Peptide receptor chemoradionuclide therapy (PRCRT), the addition of radiosensitising chemotherapy to peptide receptor radionuclide therapy (PRRT), has been used in individual centres for neuroendocrine neoplasms (NENs), but there are few data to date regarding its efficacy and safety. We conducted a systematic review to document the efficacy and side effect profile of this combination. We searched for studies including ≥5 patients with advanced NENs who received PRCRT. Major databases were searched and supplemented by handsearching of major conferences from 2019 to 2023. Data extracted included clinicopathological characteristics, trial setting and doses of chemotherapy and PRRT administered. Endpoints included overall survival (OS), progression-free survival (PFS) and adverse events (AEs); summarised qualitatively because of the marked heterogeneity in patient populations, trial designs and treatments administered. Eligible studies (24) included: 14 retrospective studies (643 patients) and 10 prospective studies (521 patients). For PRRT, most studies used ¹⁷⁷Lu (n = 21), with combination ¹⁷⁷Lu + ⁹⁰Y (n = 2), ¹¹¹In (n = 1) and ²²⁵Ac (n = 1). Chemotherapy regimens included capecitabine (n = 8), capecitabine and temozolomide (n = 5), 5-fluorouracil (n = 4) or a mixture of regimens (n = 6). Most studies included Grade 1-2 NENs. In prospective studies, median OS exceeded 2 years in most studies (range not reached by end of follow-up-86 months). In retrospective studies, median OS ranged from 7 months to 55 months and was not reached in many studies. PFS data ranged from 31 months-not reached in prospective cohorts and from 4 months-not reached in retrospective cohorts. Grade 3/4 AEs were commonly haematological, with majority being reversible or having no ongoing clinical impact. For advanced NENs, PRCRT treatment has demonstrated promising clinical outcomes and was well tolerated, although identified studies were heterogeneous. Further randomised trial data are required to clarify the place of this combination modality in the NEN treatment paradigm.