730P - The outcome of combine radioligand and CAPTEM therapy in patients with advanced, unresectable, progressive GEP-NET

Background

Prospective, single-arm, open-label, case series study evaluating efficacy and safety of combined radioligand therapy (RLT) and CAPTEM in advanced, unresectable progressive GEP-NET (NCT04194125). Primary endpoint: progression-free survival (PFS) secondary: ORR, DCR, clinical response, OS, safety.

Methods

Twenty-one patients in group of 23 screened subjects between February 2019 to May 2023 included into analysis. All patients with histopathological confirmation of GEP-NETs. Therapy consists of combine RLT (¹⁷⁷Lu DOTATOC) and CAPTEM. Disease status and treatment efficiency were evaluated by clinical assessment including PS, ORR, also biochemical response and safety profile of combine therapy.

Results

Clinical follow-up at least 48 months. Mean age 58.6 +12.6. Pancreatic (panNET) n=14, midgut n=7; NETG1=9, G2=10, G3=2. Cumulative activity ¹⁷⁷Lu (GBq) of whole therapy; median=25.1GBq (20.4-27.0), per therapy median=6.5 GBq (5.8-6.8). Median PFS for all (IQR) 31.5 months (16.0-n.r.), panNET PFS=28.0 m (14.0-n.r.), midgut PFS=31.5 m (24.5-n.r). After 6 weeks of follow-up 9 (42%) had partial response (PR) and 11 (52%) had stable disease (SD), after 3 m 9 had PR, 8 had SD, single had disease progression (DP). After 6 m 9 PR, 9 SD and 2 DP, after 12 m single 1 complete response, 10 PR, 5 SD and 2 DP. DCR after 6 weeks all patients, after 3 months 17 subjects (90%), 6 months 18 patients (85%) and after 12 months 16 subjects (89%). Clinical evaluation including 12 subjects with PS=1 improved to PS=0 in 6 subjects in 2 with PS=2 improve to PS=1, no change in 7 subjects. The most common AEs was a transient lymphopenia G2 (44%) and G3 (8%); others AEs and their significant intensity (at least G3) were observed sporadically, no G4, during and after therapy. Persistent lymphopenia noted in 16% of cases.

Conclusions

Combine therapy composed with RLT and CAPTEM is very effective therapy in advanced, GEP-NET in terms of improvement of PFS in those who had documented DP. Clinical response, DCR of combine therapy seen in most of subjects during follow-up. Significant benefit in terms of ORR reported in panNET but not in midgut. In panNET who had PR four of them had primary tumor removal, single with CR for 4 years.

Clinical trial identification

NCT04194125.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Narodowe Centrum Badań I Rozwoju (National Center for Research and Development).

Disclosure

All authors have declared no conflicts of interest.