Superior PFS results with LUTATHERA after SSA progression¹

LUTATHERA + SSA prolonged PFS in patients with grade 1/2 advanced GEP-NETs^1-3

Statistically Significant Improvement in PFS (Primary End Point)¹

^aAt primary analysis detailed in Prescribing Information for LUTATHERA.¹

Primary PFS analysis

• PFS (as assessed by independent central review according to RECIST v1.1 by radiologists unaware of the treatment), defined as the time from randomization to documented disease progression or death from any cause^2,4
• The primary PFS analysis data cutoff was July 24, 2015. Median duration of follow-up was 14 months²

GEP-NETs, gastroenteropancreatic neuroendocrine tumors; HR, hazard ratio; LAR, long-acting release; NE, not evaluable; PFS, progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors; SSA, somatostatin analogue.

PFS analysis of subgroups within the NETTER-1 trial

Prespecified subgroup analysis of PFS in the NETTER-1 trial²

PFS for LUTATHERA + SSA vs SSA alone was found to be similar to that of the overall population in NETTER-1 (HR, 0.21) in a prespecified analysis across the subgroups of extrahepatic metastases (yes [HR, 0.20]/no [HR, 0.15]), ALP (>ULN [HR, 0.21]/≤ULN [HR, 0.19]), SSTR expression (grade <4 [HR, 0.23]/grade 4 [HR, 0.18]), 5-HIAA (>2× ULN [HR, 0.15]/≤2× ULN [HR, 0.19]), CgA (>2× ULN [HR, 0.19]/≤2× ULN [HR, 0.11]), tumor grade (ENETS grade 1 [HR, 0.24]/ENETS grade 2 [HR, 0.15]), sex (male [HR, 0.24]/female [HR, 0.17]), and age (>65 years [HR, 0.24]/≤65 years [HR, 0.20]).

In a post hoc subgroup analysis of patients in the NETTER-1 trial, the impact of liver tumor burden, ALP elevation, and target lesion size on PFS was assessed for LUTATHERA + SSA vs SSA alone⁵

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

Post Hoc Subgroup Analysis of PFS in NETTER-1⁵

Analysis not powered to demonstrate a benefit between subgroups. Results should be interpreted with caution.

^aIn patients with high vs low liver tumor burden, correlation was assessed between liver function tests and baseline tumor burden. 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.^5  
bIn patients with elevated vs normal baseline ALP, correlation was assessed between PFS and serum ALP elevation. ALP was based on institutional ULN, and the log-rank test was used for within–treatment arm PFS comparisons.^5  
cNo significant difference in PFS was observed among patients with normal versus elevated ALP in the high-dose octreotide control arm (log-rank P=.0911).^5  
dPatients 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.^5  
eAmong patients treated with LUTATHERA + 30 mg octreotide LAR, 128 large tumors (>30 mm diameter) were identified, of which 89 (70%) were liver tumors. In patients treated with 60 mg octreotide, 134 large tumors were identified; 93 (69%) were liver tumors.⁵ 

5-HIAA, 5-hydroxyindoleacetic acid; ALP, alkaline phosphatase; CgA, chromogranin A; CT, computed tomography; ENETS, European Neuroendocrine Tumor Society; MRI, magnetic resonance imaging; NR, not reached; PRRT, peptide receptor radionuclide therapy; SSTR, somatostatin receptor; ULN, upper limit of normal.

Final OS analysis for LUTATHERA in NETTER-1*

OS in the ITT Population (Final Analysis)^6,a,b

^aThe prespecified final analysis of OS was completed 5 years after the last patient was randomized because this occurred before the alternative cutoff of 158 deaths (data cutoff: January 18, 2021).^6 
 bIncluded 2 patients randomized after the primary PFS analysis data cutoff (July 24, 2015). Median duration of follow-up was 76.3 months in the LUTATHERA arm and 76.5 months in the control arm.⁶

In the final OS analysis, there was no statistically significant difference in OS between the 2 treatment arms. Even though the OS results were not statistically significant, the results were clinically relevant.⁶ 

• Certain data from the final analysis are not included in the full Prescribing Information for LUTATHERA 
• At the time of the final OS analysis, which occurred 66 months after the primary PFS analysis, 117 patients were randomized to the LUTATHERA arm and 114 patients were randomized to the octreotide arm¹
• The required assumptions for the Cox model for OS were not fulfilled, therefore making the HR uninterpretable⁶

*The analysis did not meet the requirements for statistical significance.  

ITT, intent to treat; OS, overall survival.

LUTATHERA was studied in patients after disease progression on SSA therapy^1-3

NETTER-1 was a phase 3, randomized, open-label, multicenter study in well-differentiated, grade 1/2 advanced GEP-NETs after SSA progression^1,2

*Included 2 patients randomized after the primary PFS analysis data cutoff (July 24, 2015).⁶

GBq, gigabecquerel; mCi, millicurie; SSTR+, somatostain receptor-positive.

Characteristics of patients treated with LUTATHERA in NETTER-1^1-3

NETTER-1 demographics and disease characteristics were well balanced between arms

Baseline Demographics and Disease Characteristics

^aHighest SSTR tumor uptake score was based on the Krenning scale.^1-3  

NETs, neuroendocrine tumors; NOS, not otherwise specified; PS, performance score; SD, standard deviation.

In the NETTER-1 trial, ~69% of patients had grade 1 NETs and ~31% had grade 2 NETs3

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