Dr Strosberg on 212Pb-DOTAMTATE in Unresectable/Metastatic SSTR+ GEP-NETs

Jonathan Strosberg, MD, professor, Moffitt Cancer Center, discusses findings from the phase 2 ALPHAMEDIX02 trial (NCT05153772) evaluating the safety, tolerability, and efficacy of 212 Pb-DOTAMTATE in patients with somatostatin receptor (SSTR)–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

This study included 2 cohorts: patients naive to peptide receptor radionuclide therapy (PRRT; cohort 1; n = 36) and patients refractory to PRRT (cohort 2; n = 30). All patients needed to have histologically confirmed, unresectable or metastatic, SSTR-positive GEP-NETs with at least 1 site of measurable disease per RECIST 1.1 criteria.

Findings from cohort 1 presented at the 2024 ASCO Annual Meeting showed that evaluable patients not exposed to prior PRRT who received 212Pb-DOTAMTATE in the phase 1 ALPHAMEDIX01 trial (NCT03466216) or ALPHAMEDIX02 (n = 44) achieved an overall response rate (ORR) of 56.8% (95% CI, 42.2%-70.3%), which Strosberg notes is higher than ORRs typically observed in prior clinical trials investigating lutetium Lu 177 dotatate (Lutathera) in this patient population. In the phase 2 portion (n = 36), the ORR was 55.6% (95% CI, 39.6%-70.5%).

Regarding safety, the targeted alpha therapy was generally tolerable, Strosberg explains. Notably, the incidences of hematologic and renal toxicities—common concerns with PRRT—were low for patients treated with 212Pb-DOTAMTATE, he continues. Any-grade alopecia was common, occurring in 93% of patients treated in phase 1 or 2 (n = 44), and Strosberg notes that this adverse effect (AE) was usually moderate and reversible. During the presentation at the ASCO Annual Meeting, he explained that SSTR is expressed on hair follicles.

One AE that has stood out with 212Pb-DOTAMTATE is dysphagia, Strosberg continues. In evaluable patients treated during ALPHAMEDIX02 (n = 36), the rate of any-grade dysphagia was 42%, and grade 3 or 4 dysphagia was reported in 1 patient (3%). Despite normal colonoscopy findings, esophageal manometry indicated results consistent with achalasia, according to Strosberg, who adds that this AE was generally managed with palliative treatments such as Botox injections.