177Lu-Dotatate boosts PFS in Asian patients with advanced GEP-NETs

Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (¹⁷⁷Lu)-Dotatate significantly improved progression-free survival (PFS) among Asian patients with somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs), according to the LUMINET-1 study presented at ESMO Asia 2025.

The NETTER-1 and -2 phase III studies confirmed the efficacy and safety of PRRT plus octreotide for GEP-NETs, establishing PRRT as a standard treatment option in Western populations, said Dr Yun Liang of Fudan University Shanghai Cancer Center in Shanghai, China.

However, she emphasized that no comparable drug is currently approved in China, indicating a clear and pressing unmet clinical need.

Hence, Liang and her team conducted a subgroup analysis of LUMINET-1 involving 203 Asian patients with unresectable locally advanced or metastatic GEP-NETs (grade 1/2) who were randomly assigned in a 1:1 ratio to receive either ¹⁷⁷Lu-Dotatate (4 x 7.4 GBq) Q8W (n=105) or high-dose long-acting octreotide 60 mg Q4W (n=98).

In the Asian population, patients treated with ¹⁷⁷Lu-Dotatate achieved a 94-percent improvement in PFS than those receiving high-dose octreotide (stratified hazard ratio [HR], 0.06; p<0.0001 for both BICR and investigator assessments). [ESMO Asia 2025, abstract LBA3]

This PFS benefit with ¹⁷⁷Lu-Dotatate was consistently observed across all prespecified demographic and prognostic subgroups, noted Liang.

Although the overall survival (OS) data was still immature at the time of analysis, a trend towards OS improvement with ¹⁷⁷Lu-Dotatate was observed (stratified HR, 0.17; p=0.0106).

As per BICR assessment, patients on ¹⁷⁷Lu-Dotatate also demonstrated a significantly higher objective response rate (40 percent vs 2 percent; difference of 38.1 percent; p<0.0001) and disease control rate (93.3 percent vs 62.2 percent; difference of 31.4 percent; p<0.0001) compared with those on high-dose octreotide.

In terms of safety, grade ≥3 treatment-related adverse events (TRAEs) were more frequent in the ¹⁷⁷Lu-Dotatate arm than the high-dose octreotide arm (42.9 percent vs 14.3 percent), with slightly higher rates of TRAEs leading to treatment discontinuation and interruption (2.9 percent vs 1 percent for both).

Decreased white blood cell count (53.3 percent), lymphocyte count (44.8 percent), and platelet count (43.8 percent) were the most common TRAEs observed with ¹⁷⁷Lu-Dotatate.

Nevertheless, the safety findings of this study were consistent with the known safety profile for ¹⁷⁷Lu-Dotatate, with no new safety concerns identified, Liang noted.

Overall, Liang concluded that the LUMINET-1 trial met its primary endpoint of reducing the risk of progression or death by 94 percent in Asian patients, with unprecedented response rates observed with ¹⁷⁷Lu-Dotatate.

“These data have clinical practice changing implications and support the use of ¹⁷⁷Lu-DOTATATE monotherapy within the disease course of grade 1 and 2 GEP-NETs in China,” she highlighted.