211MO - First-line efficacy of [177Lu]Lu-DOTA-TATE in patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors by tumor grade and primary origin: Subgroup analysis of the phase III NETTER-2 study

Background

In the phase 3 NETTER-2 study (NCT03972488), first-line (1L) [¹⁷⁷Lu]Lu-DOTA-TATE (hereafter ¹⁷⁷Lu-DOTATATE) significantly improved median progression-free survival (PFS) by 14 months and increased objective response rate (ORR) by 34% vs high dose octreotide in patients (pts) with advanced, well-differentiated, high Grade 2 (G2) and G3, gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This preplanned subgroup analysis examined efficacy by NET grade (G2, G3) and NET origin (pancreas, small intestine [SI]).

Methods

Pts were randomized to receive 4 cycles of ¹⁷⁷Lu-DOTATATE (4 × 7.4 GBq) + 30 mg octreotide long-acting release (LAR) every 8 weeks (Q8W) during ¹⁷⁷Lu-DOTATATE treatment then Q4W (¹⁷⁷Lu-DOTATATE arm; n=151), or 60 mg octreotide LAR Q4W (control arm; n=75). Efficacy parameters (PFS, ORR, duration of response [DOR], time to response [TTR]) were centrally assessed (RECIST 1.1).

Results

For PFS and ORR, a clinical benefit in favor of ¹⁷⁷Lu-DOTATATE was evident across the subgroups (Table). In the ¹⁷⁷Lu-DOTATATE arm, median PFS was shorter for pts with G3 NETs (22.2 months [m]) vs G2 (29.0 m) and pancreatic NETs (pNETs; 19.4 m) vs SI NETs (29.0 m). ORR was high in pts with G3 NETs (48.1%) and in pts with G2 NETs (40.4%). ORR was higher for pts with pNETs (51.2%) vs SI NETs (26.7%). Among the 65 pts who had complete/partial response to ¹⁷⁷Lu-DOTATATE, median TTR was similar at ∼5.8 m for all 4 subgroups, and median DOR (95% confidence interval) was 24.9 m (23.3, not estimable [NE]) in G2 NETs, 19.3 m (17.8, NE) in G3 NETs, 18.4 m (11.3, 23.3) in pNETs and NE for SI NETs. The low number of responders in the control arm (n=7) precluded DOR and TTR subgroup analyses.

Conclusions

1L ¹⁷⁷Lu-DOTATATE efficacy was maintained across NET grades (G2, G3) and locations (pancreas, SI) and it should be considered a standard of care for this pt population. Table: 211MO

∗Kaplan-Meier estimate

Clinical trial identification

NCT03972488.

Editorial acknowledgement

Medical writing support was provided by Jo Chapman, PhD, at Aspire Scientific Ltd (Bollington, UK).

Legal entity responsible for the study

Advanced Accelerator Applications, a Novartis company.

Funding

Advanced Accelerator Applications, a Novartis Company.

Disclosure

S. Singh: Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: Ipsen, Novartis, Camurus; Financial Interests, Personal, Other, Meeting attendance support: Ipsen; Financial Interests, Personal, Invited Speaker, Meeting attendance support: Novartis. D. Halperin: Financial Interests, Personal and Institutional, Research Grant: Novartis, ITM, RayzeBio, Thermo Fisher Scientific, Camurus, Genentech/Roche; Financial Interests, Personal, Advisory Role: Novartis, TerSera, Crinetics, Amryt, Camurus, Chimeric Therapeutics, ITM, Harpoon Therapeutics, HarbourBioMed, Lantheus, Exelixis, Ipsen. S. Myrehaug: Financial Interests, Personal, Advisory Board: Novartis Oncology, Ipsen. K. Herrmann: Financial Interests, Personal, Other, Steering committee participation: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis, Sofie Biosciences; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications (a Novartis Company), Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, ITM, Janssen, Merck, Molecular Partners, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, Theragnostics, YmAbs; Financial Interests, Personal, Other, Honoraria: PeerVoice; Financial Interests, Personal, Other, Meeting Support: Janssen; Financial Interests, Personal, Advisory Board: Fusion, GE Healthcare; Financial Interests, Personal, Stocks/Shares: Sofie Biosciences. M.E. Pavel: Financial Interests, Personal and Institutional, Research Grant: Advanced Accelerator Applications (a Novartis Company), Novartis, Ipsen, ITM, Camurus, Boehringer; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications (a Novartis Company), Novartis, Ipsen, Riemser, Hutchmed; Financial Interests, Personal, Other, Honoraria: Ipsen, Advanced Accelerator Applications (a Novartis Company), Novartis, Boehringer Ingelheim, MSD, Lilly, Recordati, Sanofi, Serb; Financial Interests, Personal, Advisory Board: Crinetics, Advanced Accelerator Applications (a Novartis Company). P.L. Kunz: Financial Interests, Personal and Institutional, Research Grant: RayzeBio, Novartis; Financial Interests, Personal, Other, Honoraria: Natera, ITM, BMS, Foundation Medicine, Amgen, Genentech, Hutchmed, Ipsen, Crinetics; Non-Financial Interests, Personal, Other, Steering committee participation: RayzeBio, Exelixis; Financial Interests, Personal, Advisory Board: Amgen, Genentech, Crinetics, Hutchmed, Ipsen. B. Chasen: Financial Interests, Personal, Advisory Board: Advanced Accelerator Applications (a Novartis Company); Financial Interests, Personal, Other, Honoraria: Advanced Accelerator Applications (a Novartis Company). J. Capdevila: Financial Interests, Personal and Institutional, Research Grant: Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications (a Novartis company), Eisai, Amgen, Bayer; Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications (a Novartis Company), Amgen, Sanofi, Lilly, Hutchinson Pharma, ITM, Advanz, Merck Serono, Esteve, Roche; Financial Interests, Personal, Other, Honoraria: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications (a Novartis company), Amgen, Sanofi, Lilly, Hutchinson Pharma, ITM, Advanz, Merck Serono, Esteve, Roche. S. Tafuto: Financial Interests, Personal and Institutional, Research Grant: Ipsen, Novartis, Esteve, Camurus. D. Oh: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, Aslan, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, Idience. C. Yoo: Financial Interests, Personal and Institutional, Research Grant: Bayer, Ipsen, AstraZeneca, Boehringer Ingelheim, Servier, Eisai; Financial Interests, Personal, Other, Honoraria: Bayer, Ipsen, MSD, Merck, Celgene, AstraZeneca, GSK, Eisai, Roche, Genentech, Novartis. T.R. Halfdanarson: Financial Interests, Personal, Advisory Role: TerSera; Financial Interests, Personal, Advisory Board: Camurus, ITM, Advanced Accelerator Applications (a Novartis Company), Crinetics, Perspective Therapeutics; Financial Interests, Personal and Institutional, Other, Research support: Camurus, ITM, Advanced Accelerator Applications (a Novartis Company), Crinetics, Perspective Therapeutics, Thermo Fisher Scientific. I. Folitar, Y. Zhang: Financial Interests, Personal, Stocks/Shares: Novartis; Financial Interests, Personal, Full or part-time Employment: Novartis. W.W. de Herder: Financial Interests, Personal, Advisory Role: Ipsen, Novartis, Advanced Accelerator Applications (a Novartis Company), ITM; Financial Interests, Personal, Other, Honoraria: Ipsen, Novartis, Advanced Accelerator Applications (a Novartis Company). D. Ferone: Financial Interests, Personal and Institutional, Research Grant: Camurus, Pfizer; Financial Interests, Personal, Other, Honoraria: Novartis, Recordati Rare Diseases; Financial Interests, Personal, Advisory Board: Camurus, Ipsen, Novartis, Recordati Rare Diseases, Pfizer. All other authors have declared no conflicts of interest.