Aims
The addition of chemotherapy (CT) to PRRT in NENs has been used in Australian centres 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.
Methods
All eligible studies included at least 5 patients with advanced NENs of any primary and grade who received PRRT and CT. Major databases were searched and supplemented by handsearching major conferences from 2019-2020. Endpoints included overall survival (OS), progression-free survival (PFS) and adverse events (AEs); summarised qualitatively because of the marked heterogeneity in trial design, patient population, treatment regimens and clinical outcome measures.
Results
Eligible studies (22) included: 13 retrospective studies (567 patients) and 9 prospective cohort studies (423 patients). Most studies used Lu-177 (n=21), including 2 studies which used Lu-177 with Y-90, while one study used I-111. Individual studies often included patients on different CT regimens, including capecitabine (n=12), capecitabine and temozolomide (n=8) or 5-fluorouracil (n=8). Most studies included Grade 1-2 NENs.
In prospective studies, median OS often exceeded the average of 2-3 years of follow-up (range 31 months - not reached (NR) by end of follow up). In retrospective studies, median OS ranged from 7 months (highly aggressive G3 subpopulation (Ki-67 > 55%)) - 62 months (mixed population with more G1-2 tumours), and NR in many studies. PFS data ranged from 31 months - NR in prospective cohorts and from 4 months - NR in retrospective cohorts.
Grade 3/4 AEs were commonly haematological and the majority were reversible or had no ongoing clinical impact.
Conclusions
The addition of radiosensitising CT to PRRT demonstrated promising clinical outcomes and was tolerated well, although identified studies were heterogeneous. Forthcoming randomised trial data will clarify the place of this combination modality in the NEN treatment paradigm.