Dr Kunz on Time to Response With Lutetium Lu 177 Dotatate in GEP-NETs

Pamela L. Kunz, MD, associate professor, internal medicine (medical oncology), Yale School of Medicine; director, Center for Gastrointestinal (GI) Cancers, chief, GI Medical Oncology, Smilow Cancer Hospital, Yale Cancer Center, discusses findings from a subanalysis of the phase 3 NETTER-2 study (NCT03972488) investigating frontline lutetium Lu 177 dotatate (Lutathera) in patients with advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

In NETTER-2, 226 patients with newly diagnosed and somatostatin receptor–positive advanced GEP-NETs were randomly assigned 2:1 to receive either lutetium Lu 177 dotatate plus octreotide long-acting repeatable (LAR) or octreotide LAR alone. This subanalysis evaluated time to response with the radioligand therapy, as well as additional safety data. Among 65 responders in the lutetium Lu 177 dotatate arm, the median time to response was 5.7 months (range, 4.1-8.3). Most responses occurred during the 4 cycles of treatment with lutetium Lu 177 dotatate.

Because it typically takes a longer time to induce objective responses with radioligand therapy compared with treatments such as cytotoxic chemotherapy, Kunz says that this relatively short median time to response was encouraging. Therefore, patients who need quick objective responses may particularly benefit from treatment with lutetium Lu 177 dotatate, as they may respond within an average of 3 treatment cycles, Kunz concludes.

Additionally, the patterns of adverse effects (AEs) observed in the lutetium Lu 177 dotatate arm were consistent with the established safety profile of the radioligand therapy. Observed laboratory abnormalities included grade 3/4 decreases in lymphocytes (lutetium Lu 177 dotatate arm, 38.1%; control arm, 2.7%), leukocytes (4.1%; 0%), neutrophils (3.4%; 0%), platelets (2.0%; 0%), and hemoglobin (1.4%; 2.7%). Among patients with immediate hematotoxicities, the median time to first occurrence of hematologic toxicities was 4.4 months. Infection rates were similar between the 2 arms. One patient, who received lutetium Lu 177 dotatate, developed myelodysplastic syndrome approximately 14 months after their first cycle of therapy. Five fatal AEs occurred during treatment, 3 in the lutetium Lu 177 dotatate arm and 2 in the control arm, all of which were attributed to GEP-NET progression and determined to be unrelated to treatment.