In a French phase II noncomparative trial (OCLURANDOM) reported in The Lancet Oncology, Baudin et al found that lutetium Lu-177 dotatate (Lu-177 dotatate) produced numerically better progression-free survival results than those achieved with sunitinib when used as an internal control in patients with previously treated somatostatin receptor–positive metastatic pancreatic neuroendocrine tumors.
Study Details
In the multicenter open-label trial, 84 patients were randomly assigned between February 2015 and July 2020 to receive Lu-177 dotatate at 7.4 GBq every 8 weeks up to four cycles with concomitant amino acid infusion (n = 41) or oral sunitinib at 37.5 mg once daily (n = 43). Crossover after disease progression was permitted. The primary endpoint was progression-free survival at 12 months on central review in the intent-to-treat population.
Key Findings
Progression-free survival at 12 months was found in 33 (80.5%, 90% confidence interval [CI] = 67.5–89.9%) of 41 patients in the Lu-177 dotatate group and in 18 (41.9%, 90% CI = 29.1%–55.5%) of 43 patients in the sunitinib group. Median progression-free survival was 20.7 months (95% CI = 17.1–25.5 months) in the Lu-177 dotatate group and 11.0 months (95% CI = 8.7–13.7 months) in the sunitinib group.
Grade 3 or 4 adverse events occurred in 44% of the Lu-177 dotatate group and 72% of the sunitinib group; the most common were hypertension (10%), lymphopenia (7%), and nausea (7%) in the Lu-177 dotatate group, and neutropenia (31%), hypertension (19%), and leukopenia (16%) in the sunitinib group. Drug-related serious adverse events occurred in 15% vs 23% of patients. A 10.3-point (95% CI = 2.4–18.2 point) difference in Global Health Status score favored the Lu-177 dotatate group. Late adverse events (grade 2 or worse) were reported in 24 (60%) of 40 patients in the Lu-177 dotatate group and in 3 (43%) of 7 patients in the sunitinib group. One treatment-related death (due to acute leukemia) occurred in the Lu-177 dotatate group.
The investigators concluded: “Using sunitinib as an internal control, our results show clinically significant antitumor efficacy of [Lu-177 dotatate] in pretreated, progressive, somatostatin receptor–positive, metastatic pancreatic neuroendocrine tumors, and a better quality of life during the treatment phase. Late adverse events were reported in the Lu-177 dotatate group that might affect the tolerance of subsequent lines of treatment.”
Eric Baudin, MD, of the Department of Imaging, Endocrine Oncology Unit, Gustave Roussy, University Paris Saclay, Villejuif, France, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by the French Ministry of Health, through the National Institute for Cancer. For full disclosures of the study authors, visit thelancet.com.
