177Lu-DOTATATE is licensed for gastroenteropancreatic (GEP-)NETs. PRELUDE is an international retrospective study (NCT02788578) to describe LAN use with 177Lu-PRRT (LAN–PRRT) in advanced NETs. Here we report effectiveness results, including a post hoc TGR analysis to complement RECIST-based progression measures.
Analysis of patients (pts) receiving LAN with 177Lu-DOTATATE/DOTATOC followed by LAN only. Key inclusion criteria: metastatic/locally advanced, grade 1/2, somatostatin receptor-positive GEP-/lung NET, progressive disease (PD) within 12 mo and within 6 mo before LAN–PRRT start (assessed locally), ≥1 LAN injection 8 wks before LAN–PRRT start, continuous LAN use during LAN–PRRT, cumulative PRRT activity ≥500 mCi. Primary endpoint: progression-free survival (PFS) rate at end of last LAN–PRRT cycle (RECIST v1.1, central review). Key secondary endpoints: PFS rate at last available follow-up (RECIST v1.1 central review), best overall response (OR; RECIST v1.1 central review). Post hoc analysis: TGR (% variation of tumour volume/mo) calculated from sum of longest diameter of target lesions between two MRI/CT scans during: prebaseline/baseline (within 12 mo and within 6 mo before baseline), baseline/end of last LAN–PRRT cycle (within 6 mo before baseline and end of last LAN–PRRT cycle), and end of last LAN–PRRT cycle/last available follow-up visit.
Enrolment terminated early (insufficient recruitment): 40 pts (GEP n = 39; lung n = 1) (full analysis set: GEP n = 23, lung n = 1). LAN exposure and effectiveness results in GEP-NETs are shown in the table. Waterfall plots of prebaseline/baseline TGR showed individual progressions and regressions, with a mean of 0 [–1.4; 1.5].Table: 1331P
|Patients with GEP-NETs (n = 23)|
|Median (range) LAN exposure, mo Overall Prior to LAN–PRRT During LAN–PRRT During LAN only follow-up||37.0 (16.7–90.0) 10.5 (0.7–61.7) 14.2 (7.0–24.0) 12.6 (6.1–32.5)|
|PFS rate [95% CI] at end of last LAN–PRRT cycle||91.7% [53.9; 98.8]|
|PFS rate [95% CI] at last available follow-up (up to 12 mo post-treatment)||95.0% [69.5; 99.3]|
|Best OR [95% CI] RECIST v1.1||Partial response (PR): 34.8% [18.8; 55.1] Stable disease: 60.9% [40.8; 77.8] PD: 4.3% [0.8; 21.0]|
|Mean [95% CI] TGR: Prebaseline/baseline Baseline/end of last LAN–PRRT cycle End of last LAN–PRRT cycle/last available follow-up visit||0.0% [–1.4; 1.5] –1.6% [–2.7; –0.4] –0.2% [–1.3; 0.9]|
Effectiveness data were encouraging in this small selected population. TGR suggested tumour regression during LAN–PRRT. Despite low baseline TGR, 35% pts had RECIST PR on central assessment.
Clinical trial identification
Legal entity responsible for the study
Writing and editorial/submission support provided by Tom Vizard, PhD, and Richard McDonald (Watermeadow Medical), funded by Ipsen.
V. Prasad: Honoraria: Bayer, Ipsen, ITG; Consultant: Bayer, Ipsen, ITG. C.M. Grana: Consultant: Norgine; Other: Ipsen, Novartis, Iason. T. Shah: Honoraria: Ipsen; Consultant: Ipsen. A. Lamarca: Speaker's bureaux: Ipsen. F. Courbon: Advisory board member: Norgine; Grant recipient: AAA, Bayer; Speaker's bureaux: AAA, Bayer, GEHC, Ipsen, Novartis; Other: Cyclopharma. K. Scheidhauer: Honoraria: Ipsen, Shire. Consultant: Eisa, Ipsen, Novartis, Shire. E. Baudin: Honoraria: Ipsen, Novartis, Pfizer; Consultant, Grant recipient: AAA, Ipsen, Novartis, Pfizer. X.-M. Truong-Thanh: Employee, Stock owner: Ipsen. A. Houchard: Grant recipient, Employee, Stock owner: Ipsen. L. Bodei: Honoraria, Consultant, Speaker's bureaux: AAA, Ipsen. All other authors have declared no conflicts of interest.