1148MO - A multivariate efficacy analysis of [177Lu]Lu-DOTA-TATE in the NETTER 2 study

Background

NETTER-2 demonstrated a progression-free survival (PFS) and objective response rate (ORR) benefit favoring [¹⁷⁷Lu]Lu-DOTA-TATE + octreotide 30 mg long-acting release (LAR) (¹⁷⁷Lu-DOTATATE) vs octreotide 60 mg LAR (control) in the first line setting in patients with advanced, well differentiated, Grade 2 (G2) and G3 (Ki67 ≥10%– ≤55%), gastroenteropancreatic neuroendocrine tumors (NETs). Overall, 53.5% of patients had extensive disease outside the liver. This analysis aimed to assess the effect of ¹⁷⁷Lu-DOTATATE when adjusted for baseline (BL) covariates, including disease spread, and identify potential prognostic factors.

Methods

A multivariate Cox regression model (PFS) and logistic regression model (ORR) were applied to select BL covariates of: age (<65 vs ≥65 years); sex (male vs female); primary NET site (pancreas [pNET] vs small intestine [SI] vs other); NET grade (G2 vs G3 low [Ki67 ≤30%] vs G3 high [Ki67 >30%]); Ki67 as continuous variable; metastatic spread (liver metastases only [± lymph nodes] vs other metastases); chromogranin A (CgA) (≤2 × upper limit of normal [ULN] vs >2 × ULN); somatostatin receptor (SSTR) uptake score (3 [>liver, spleen]).

Results

Treatment effects in PFS and ORR were minimally affected when adjusted for covariates. PFS hazard ratios (95% CI) with vs without adjusting BL covariates were 0.212 (0.134, 0.337) vs 0.276 (0.182, 0.418); ORR odds ratios (95% CI) were 10.43 (3.98, 27.29) vs 7.81 (3.32, 18.40). The table shows BL covariates that notably affected PFS and ORR (p value

Conclusions

¹⁷⁷Lu-DOTATATE efficacy benefits were consistent after adjustment for BL covariates. Potential prognostic factors have been identified.

Clinical trial identification

NCT03972488.

Editorial acknowledgement

Medical writing support was provided by Jo Chapman, PhD, at Aspire Scientific Ltd (Bollington, UK), and funded by Advanced Accelerator Applications, a Novartis Company.

Legal entity responsible for the study

Advanced Accelerator Applications, a Novartis Company.

Funding

Advanced Accelerator Applications, a Novartis Company.

Disclosure

M.E. Pavel: Financial Interests, Personal and Institutional, Research Grant: Advanced Accelerator Applications (a Novartis company), Novartis, Ipsen, ITM, Camurus and Boehringer; Financial Interests, Personal, Advisory Role: Advanced Accelerator Applications (a Novartis company), Novartis, Ipsen, Riemser and Hutchmed, honoraria from Ipsen, Advanced Accelerator Applications (a Novartis company), Novartis, Boehringer, MSD, Lilly, Recordati, Sanofi and Serb; Financial Interests, Personal, Advisory Board: Crinetics and Advanced Accelerator Applications (a Novartis company). D. Ferone: Financial Interests, Personal and Institutional, Research Grant: Camurus and Pfizer; Financial Interests, Personal, Other, Honoraria: Novartis and Recordati Rare Diseases; Financial Interests, Personal, Advisory Board: Camurus, Ipsen, Novartis, Recordati Rare Diseases and Pfizer. D. Halperin: Financial Interests, Personal and Institutional, Research Grant: Novartis, ITM, RayzeBio, Thermo Fisher Scientific, Camurus and Genentech/Roche; Financial Interests, Personal, Advisory Role: Novartis, Tersera, ITM, Crinetics, Amryt, Camurus, Chimeric Therapeutics, Harpoon Therapeutics, HarbourBioMed, Lantheus, Exelixis and Ipsen. S. Myrehaug: Financial Interests, Personal, Advisory Board: Novartis Oncology and Ipsen. K. Herrmann: Financial Interests, Personal, Steering Committee Member: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis and 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, ; Financial Interests, Personal, Other, Honoraria: PeerVoice; Financial Interests, Personal, Other, Meeting support: Janssen; Financial Interests, Personal, Advisory Board: Fusion and GE healthcare ; Financial Interests, Personal, Stocks or ownership: Sofie Biosciences, Pharma15, NVision, Convergent, Aktis Oncology and AdvanCell. P.L. Kunz: Financial Interests, Personal and Institutional, Research Grant: RayzeBio and Novartis; Financial Interests, Personal, Other, Honoraria: Natera, ITM, BMS, Foundation Medicine, Amgen, Genentech, Crinetics, HutchMed and Ipsen; Non-Financial Interests, Personal, Steering Committee Member: RayzeBio and Exelixis; Financial Interests, Personal, Advisory Board: Amgen, Genentech, Crinetics, HutchMed and 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 Castillon: Financial Interests, Personal and Institutional, Research Grant: Novartis, Pfizer, AstraZeneca, Advanced Accelerator Applications (a Novartis company), Eisai, Amgen and 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 and 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 and 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 and Handok and advisory board participation for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yu. C. Yoo: Financial Interests, Personal and Institutional, Research Grant: Bayer, Ipsen, AstraZeneca, Boehringer Ingelheim, Servier and Eisai; Financial Interests, Personal, Other, Honoraria: Bayer, Ipsen, MSD, Merck, Celgene, AstraZeneca, GSK, Eisai, Roche, Genentech and Novartis. T.R. Halfdanarson: Financial Interests, Personal, Advisory Role: TerSera; Financial Interests, Personal and Institutional, Research Funding: Camurus, ITM, Advanced Accelerator Applications (a Novartis company), Crinetics, Perspective Therapeutics and Thermo Fisher Scientific; Financial Interests, Personal, Advisory Board: Camurus, ITM, Advanced Accelerator Applications (a Novartis company), Crinetics, Perspective Therapeutics. 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 and Advanced Accelerator Applications (a Novartis company) and ITM; Financial Interests, Personal, Other, Honoraria: Ipsen, Novartis and Advanced Accelerator Applications (a Novartis company). S. Singh: Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal, Advisory Role: Ipsen, Novartis and Camurus; Financial Interests, Personal, Other, Meeting attendance support: Ipsen and Novartis. All other authors have declared no conflicts of interest.