Lutathera Met Primary Endpoints in Progression Free Survival for Gastroenteropancreatic Neuroendocrine Tumors

Lutetium Lu¹⁷⁷ dotatate (Lutathera; Novartis) met its primary endpoint in the phase 3 NETTER-2 trial (NCT03972488), including significant improvements in progression free survival (PFS) for those with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). In the study, investigators included individuals with newly diagnosed somatostatin receptor (SSTR)-positive, grades 2 and 3 advanced GEP-NETs who were treated with lutetium Lu¹⁷⁷ dotatate and long-acting octreotide or high-dose long-acting octreotide alone.¹

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“These positive results for [lutetium Lu¹⁷⁷ dotatate] are quite remarkable, and they represent the potential for radioligand therapy to make a meaningful impact for newly diagnosed patients living with advanced GEP-NETs,” Jeff Legos, PhD, MBA, executive vice president of Global Head of Oncology Development at Novartis, said in the statement. “Exploring the use of radioligand therapies in earlier lines of treatment for patients with cancer is part of our larger, collaborative effort to precisely deliver novel treatment modalities directly to the cancer cells to improve patient outcomes.”¹

The phase 3 trial was an open-label, multi-center, randomized study, evaluating the drug combination as a first line treatment and its effect on PFS. Participants were diagnosed with SSTR-positive advanced GEP-NETs within 6 months before their enrollment. The results of the study will be presented at an upcoming medical meeting and shared with regulatory authorities, according to a statement from Novartis.¹

Lutetium Lu¹⁷⁷ dotatate is approved for treatment in the United States for SSTR-positive GEP-NETs, which can include foregut, midgut, and hindgut tumors. In the European Union, it is approved for unresectable or metastatic, progressive, well-differentiated SSTTR-positive GEP-NETs in adults.¹

The initial approval of lutetium Lu¹⁷⁷ dotatate in the United States was based on the NETTER-1 trial (NCT01578239). The results demonstrated significant and clinically meaningful PFS prolongation for those who were treated with the study drug combination compared to high-dose long-acting octreotide alone for those with SSTR-positive and inoperable midgut NETs, which were progressing despite the standard of care.¹

According to the results published in the New England Journal of Medicine, the estimated PFS at 20 months was 65.2% in the lutetium Lu¹⁷⁷ dotatate group compared to only 10.8% in the control group. Furthermore, the response rate was 18% and 3%, respectively.²

In the interim analysis for overall survival, there were 14 deaths in the lutetium Lu¹⁷⁷ dotatate group compared to 26 in the control group.²

There were no new safety signals identified in the NETTER-2 trial, establishing a similar safety profile as previously reported.¹ In the NETTER-1 trial, investigators found that neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9% of patients, respectively. There were no reports of these adverse effects in the control group. Additionally, there was no evidence of renal toxic effects in the observed study time.²

Furthermore, the study authors also reported that myelosuppression occurred in less than 10% of individuals in the lutetium Lu¹⁷⁷ dotatate group.²

Lutetium Lu¹⁷⁷ dotatate is the first radioligand therapy that has demonstrated clinically meaningful benefits in the first line setting, according to the statement from the company.¹ Novartis will continue to investigate radioligand therapies in GEP-NETs and other cancers, such as prostate, breast, lung, pancreatic, and colon.¹

References

1. Novartis radioligand therapy Lutathera demonstrated statistically significant and clinically meaningful progression-free survival in first line advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). News release. Novartis. September 25, 2023. Accessed September 26, 2023. https://www.novartis.com/news/media-releases/novartis-radioligand-therapy-lutathera-demonstrated-statistically-significant-and-clinically-meaningful-progression-free-survival-first-line-advanced-gastroenteropancreatic-neuroendocrine-tumors-gep-nets
2. Strosberg J, El-Haddad G, Wolin E, Hendifar A, et al. Phase 3 trial of 177lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125-135. doi:10.1056/NEJMoa1607427