In an interim analysis of a National Institutes of Health phase II study reported in the Journal of Clinical Oncology, Lin et al found that lutetium Lu-177 dotatate (Lu-177 dotatate) was active in progressive metastatic pheochromocytomas and paragangliomas (PPGLs).
As stated by the investigators, “[Lu-177 dotatate] is a somatostatin receptor (SSTR)–targeting radiopharmaceutical that shows promise for treating metastatic…PPGLs, a rare SSTR-expressing tumor.”
Study Details
In the study, 36 evaluable patients with metastatic PPGL with progression within 12 months were enrolled between October 2017 and July 2022; patients were prospectively recruited into two genetic cohorts: succinate dehydrogenase (SDHx)–mutated disease (n = 18) and apparent sporadic disease (n = 18). Lu-177 dotatate was given once every 8 weeks for four cycles at a fixed dose of 7.4 GBq. Patients with systolic blood pressure > 200 mmHg despite medical management were treated in the intensive care unit (ICU). The primary endpoint was progression-free survival at 6 months from initiation of treatment.
Key Findings
Among all patients, 6-month progression-free survival was 86.1% (95% confidence interval [CI] = 75.5%–98.2%); the rate was significantly lower (P = .009) in the SDHx group (72.0%, 95% CI = 54.2%–96.2%) vs the sporadic group (100%, 95% CI = 100%–100%).
Best response was achieved at an average of 11.0 months after completing Lu-177 dotatate treatment, with 10 patients (27.8%; including 6 in the SDHx group and 4 in the sporadic group) achieving partial response as best response.
Among all patients, median progression-free survival was 19.9 months, including 12.9 months in the SDHx group vs 24.3 months in the sporadic group (P = .162). Median overall survival was 51.7 months among all patients, including 31.2 months in the SDHx group vs not reached in the sporadic group (P = .110).
Among 39 patients in the safety population, grade ≥ 3 treatment-related adverse events occurred in 69%, most commonly lymphopenia (61%). Grade ≥ 3 catecholamine release syndrome was observed in 17% of patients. No treatment-related deaths were reported.
The investigators concluded: “[Lu-177 dotatate] demonstrated effectiveness and acceptable safety profile for progressive, metastatic PPGL. [Catecholamine release syndrome] may occur but can be mitigated through pretreatment with antihypertensives, and, when appropriate, intensified monitoring in the ICU with intravenous antihypertensives.”
Frank I. Lin, MD, of Molecular Imaging Branch, National Institutes of Health, National Cancer Institute, Center for Cancer Research, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Institutes of Health. For full disclosures of all study authors, visit ascopubs.org.
