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Efficacy

Post Hoc Progression-Free Survival

PFS Within Subgroups of the NETTER-1 Trial8

In a post hoc subgroup analysis of patients in the NETTER-1 trial, the impact of liver tumor burden, alkaline phosphatase (ALP)8 elevation, and target lesion size on PFS was assessed in the 177Lu-Dotatate plus high-dose octreotide arm vs control.

Results are based on a post hoc analysis of the key primary endpoint and are observational in nature; as such, they were not powered to show statistical significance.

PFS by extent of liver tumor burden

In patients with high vs low tumor burden, correlation was assessed between liver function tests and baseline tumor burden*:

Median PFS was NR vs 5.4 months8

  • High Tumor Burden (>50%): Median PFS was NR (n=19) vs 5.4 months in the control arm (n=30)

Median PFS was NR vs 9.1 months8

  • Low Tumor Burden (<25%): Median PFS was NR (n=71) vs 9.1 months in the control arm (n=70)

*Findings in patients with tumor burden >50% do not translate to results in patients with extreme tumor burden (eg, >90%). A limitation of this study was that central readers did not specify patients with extreme tumor burden (>90%), and therefore no specific safety analysis in that subgroup was possible.8

PFS by normal or elevated ALP

In patients with elevated vs normal baseline ALP, correlation was assessed between PFS and serum ALP elevation†‡:

Median PFS was NR vs 8.5 months8

  • Normal ALP Baseline Group: Median PFS was NR (n=71) vs 8.5 months in the control arm (n=75)

Median PFS was NR vs 5.8 months8

  • Elevated Baseline ALP Group: Median PFS was NR (n=41) vs 5.8 months in the control arm (n=37)

Normal or > ULN. ALP was based on institutional ULN, and the log-rank test was used for within–treatment arm PFS comparisons.8 
No significant difference in PFS was observed among patients with normal versus elevated ALP in the high-dose octreotide control arm (log-rank P=.0911).8

PFS by presence or absence of a large lesion

Patients were stratified into 2 subgroups based on the presence or absence of at least 1 target lesion >30 mm in diameter at any body site on CT or MRI at baseline§∥:

Median PFS was NR vs 8.5 months8

  • Presence of ≥1 Large Tumors (>30 mm diameter): Median PFS was NR (n=79) vs 8.5 months in the control arm (n=74)

Median PFS was NR vs 8.3 months8

  • Absence of Large Tumors (<30 mm diameter): Median PFS was NR (n=37) vs 8.3 months in the control arm (n=39)

§Patients were stratified into 2 subgroups based on the presence or absence of at least 1 target lesion >30 mm in diameter at any body site on CT or MRI at baseline. The approximate size threshold has been described in previous literature as distinguishing "large" tumors from smaller ones in animal studies of PRRT.8 
Among target lesions in patients within the 177Lu-Dotatate arm, 128 large tumors (>30 mm diameter) were identified, of which 89 (70%) were liver tumors; in the high-dose octreotide arm, 134 large tumors were identified; 93 (69%) were liver tumors.8

5-HIAA, 5-hydroxyindoleacetic acid; CgA, chromogranin A; CrCL, creatinine clearance; CT, computed tomography; FDA, US Food and Drug Administration; GEP-NET, gastroenteropancreatic neuroendocrine tumor; HR, hazard ratio; IM, intramuscular; ITT, intent to treat; IV, intravenous; MRI, magnetic resonance imaging; NE, not evaluable; NETs, neuroendocrine tumors; NR, not reached; PRRT, peptide receptor radionuclide therapy; RECIST, Response Evaluation Criteria in Solid Tumors; RLT, radioligand therapy; SSTR, somatostatin receptor; ULN, upper limit of normal.

Important Safety Information

WARNINGS AND PRECAUTIONS

  • Radiation Exposure: Treatment with LUTATHERA contributes to a patient’s overall long-term cumulative radiation exposure and is associated with an increased risk for cancer...

Indication

LUTATHERA® (lutetium Lu 177 dotatate) is indicated for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut...

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References: 1. Lutathera. Prescribing information. Novartis Pharmaceuticals Corp. 2. Strosberg J, El-Haddad G, Wolin E, et al; for the NETTER-1 trial investigators. Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. 3. Strosberg JR, Caplin ME, Kunz PL, et al; NETTER-1 investigators. 177Lu-dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021;22(12):1752-1763. 4. US Food and Drug Administration. FDA approves new treatment for certain digestive tract cancers [press release]. January 26, 2018. Accessed February 24, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-certain-digestive-tract-cancers 5. Hope TA, Bodei L, Chan JA, et al. NANETS/SNMMI consensus statement on patient selection and appropriate use of 177Lu-DOTATATE peptide receptor radionuclide therapy. J Nucl Med. 2020;61(2):222-227. 6. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. 7. Strosberg J, Srirajaskanthan R, El-Haddad G, et al; NETTER-1 study group. Symptom diaries of patients with midgut neuroendocrine tumors treated with 177Lu-DOTATATE. J Nucl Med. 2021;62:1712-1718. 8. Strosberg J, Kunz PL, Hendifar A, et al; NETTER-1 study group. Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-dotatate: an analysis of the NETTER-1 study. Eur J Nucl Med Mol Imaging. 2020;47(10):2372-2382.