The FDA granted final approval to Lutetium Lu 177 dotatate biosimilar for patients with SSTR-positive GEP-NETs.
The FDA has granted final approval to lutetium Lu 177 dotatate (Bravnetsa; PNT2003), a lutetium Lu 177 dotatate (Lutathera) biosimilar for the treatment of adult patients with somatostatin receptor (SSTR)–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut NETs.1
The agent was approved through the FDA's abbreviated new drug application pathway, and the agency determined it to be bioequivalent and therapeutically equivalent to the reference product.
“As the only radiopharmaceutical the FDA has determined to be bioequivalent and therapeutically equivalent to lutetium Lu 177 dotatate approved in the United States, [the biosimilar’s] approval marks an important milestone, bringing additional treatment options to people living with GEP-NETs,” Mary Anne Heino, executive chairperson of Lantheus, said in a news release. “We are focused on a thoughtful launch and ensuring the right commercial and operational capabilities are in place to support reliable supply and broad patient access.”
Efficacy data for lutetium Lu 177 dotatate in GEP-NETs come from the phase 1/2 ERASMUS study, where the agent was first provided at a single site under a general peptide receptor radionuclide therapy expanded-access program.3
Overall, 1214 patients received lutetium Lu 177 dotatate in ERASMUS. Of these, 578 had baseline tumor assessments, and 360 of those patients had GEP-NETs and long-term follow-up. Within that group, 145 patients underwent prospective tumor evaluations per RECIST criteria.
Patients received the lutetium Lu 177 dotatate injection specifically, at 7.4 GBq (200 mCi) every 6 to 13 weeks for a maximum of 4 doses, with concurrent amino acid solution.
The primary end point was investigator-assessed overall response rate (ORR).
In the efficacy-evaluable population, the median age was 60 years (range, 30-85), and 51% of patients were men. In total, 71% had a baseline Karnofsky performance status of at least 90, and 51% had disease progression within 12 months of treatment. Prior chemotherapy had been given to 7% of patients, and 52% received a concomitant somatostatin analog. The median dose received was 29.6 GBq (800 mCi).
The investigator-assessed ORR was 17% (95% CI, 13%-21%), in addition to 3 complete responses. This analysis required responders to have undergone prospective response assessments per RECIST criteria. Among responders (n = 60), the median duration of response (DOR) was 35 months (95% CI, 17-38).
The biosimilar’s label draws on data from the phase 3 NETTER-1 (NCT01578239) trial and ERASMUS.1
NETTER-1 compared lutetium Lu 177 dotatate plus long-acting octreotide with high-dose, long-acting octreotide alone. Myelosuppression was more frequent in the lutetium Lu 177 dotatate arm. Rates of all-grade and grade 3 or 4 adverse effects (AEs) such as anemia, thrombocytopenia, and neutropenia in the lutetium Lu 177 in arm were 81% and 0%, 53% and 1%, and 26% and 3%, respectively.
Of the 59 patients who developed thrombocytopenia, 68% had platelet recovery, with a median time to recovery of 2 months. At a median follow-up of 76 months, secondary myelodysplastic syndrome (MDS) was reported in 2.3% of patients receiving lutetium Lu 177 dotatate vs none in the high-dose, long-acting octreotide arm.
In ERASMUS, 2% of patients developed secondary MDS, with 0.5% of patients developing acute leukemia. The median time to onset was 29 months (range, 9-45) for secondary MDS and 55 months (range, 32-125) for acute leukemia. Moreover, renal failure occurred in 8 patients between 3 and 36 months after treatment.
Common grade 3 or 4 AEs reported with lutetium Lu 177 dotatate were lymphopenia, vomiting, and nausea, with these being reported at a higher incidence with the biosimilar.
