Abstract
Despite the benefit of peptide receptor radionuclide therapy (PRRT) for patients with well-differentiated neuroendocrine tumors (WD NETs), no clinical metric to anticipate benefit from the therapy for individual patients has been previously defined. To assess whether the prognostic ability of the clinical score (CS) could be validated in an external cohort of patients with WD NETs. This multicenter cohort study's analysis included patients with WD NETs who were under consideration for peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-dotatate between March 1, 2016, and March 17, 2020. The original cohort included patients from Vanderbilt-Ingram Cancer Center. The validation cohort included patients from Ochsner Medical Center, Markey Cancer Center, and Rush Medical Center. Patients with paragangliomas, pheochromocytomas and neuroblastomas were excluded. Statistical analysis was performed from June to November 2021. PRRT with 177Lu-dotatate or alternate therapies such as everolimus, sunitinib, or capecitabine plus temozolomide. The primary outcome was progression-free survival (PFS) and was estimated by the Kaplan-Meier method; a Cox proportional-hazards model adjusting for primary tumor site, tumor grade, and number of PRRT doses administered was used to analyze association between CS and outcomes. A total of 126 patients (median age [IQR] age: 63.6 [52.9-70.7] years; 64 male individuals) were included in the validation cohort, and the combined cohort (validation and original cohorts combined) had a total of 248 patients (median [IQR] patient age: 63.3 [53.3-70.3] years; 126 male individuals). In the validation cohort, on multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.61; 95% CI, 1.64-4.16). After finding an association of the CS with PFS in the validation cohort, the original and validation cohorts were combined into the cohort for this analysis. On multivariable analysis, for each 2-point increase in CS, PFS decreased significantly (hazard ratio, 2.52; 95% CI, 1.89-3.36). Increases in CS were associated with worsening PFS in the validation cohort, validating findings from the original cohort. These findings suggest that the CS, to our knowledge, represents the first clinical metric to estimate anticipated benefit from PRRT for patients with WD NETs and may be a clinical tool for patients being considered for PRRT.
Highlights
Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-dotatate has garnered regulatory licensure in Europe and the United States for the treatment of somatostatin receptor– positive gastroenteropancreatic neuroendocrine tumors (NETs) and has demonstrated antitumor activity in somatostatin receptor positive NETs from other primary sites.[1,2,3] Despite the benefit from 177Lu-dotatate, questions remain about when to sequence the therapy for patients in relation to other available therapies, and which patients are optimal candidates for the therapy
Increases in clinical score (CS) were associated with worsening progression-free survival (PFS) in the validation cohort, validating findings from the original cohort
These findings suggest that the CS, to our knowledge, represents the first clinical metric to estimate anticipated benefit from peptide receptor radionuclide therapy (PRRT) for patients with well-differentiated neuroendocrine tumors (WD NETs) and may be a clinical tool for patients being considered for PRRT
Summary
Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (177Lu)-dotatate has garnered regulatory licensure in Europe and the United States for the treatment of somatostatin receptor– positive gastroenteropancreatic neuroendocrine tumors (NETs) and has demonstrated antitumor activity in somatostatin receptor positive NETs from other primary sites.[1,2,3] Despite the benefit from 177Lu-dotatate, questions remain about when to sequence the therapy for patients in relation to other available therapies, and which patients are optimal candidates for the therapy. The prospective studies comparing PRRT with targeted agents are years away from results being available and still may not define the optimal time point to administer the therapy for a given patient.[4] PRRT may be associated with unacceptable toxicity for patients with disease involving certain sites or baseline comorbidities.[5,6,7,8] To date, no prognostic scoring system has been developed to anticipate patient benefit from PRRT. We found the CS to be associated with progression-free survival (PFS) in patients treated with 177Lu-dotatate.[9] In this manuscript, we present our efforts to validate the CS and establish it as the first clinical metric that can estimate the anticipated benefit from 177Ludotatate for patients
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