In an Italian retrospective cohort study reported in JAMA Network Open, Pusceddu et al found that upfront peptide receptor radionuclide therapy (PRRT) was associated with better progression-free survival vs upfront chemotherapy or targeted therapy in patients with advanced well-differentiated enteropancreatic neuroendocrine tumors.
Study Details
The study involved data on 508 patients with unresectable locally advanced or metastatic grade 1 to 3 disease from multiple Italian centers who had disease progression after treatment with somatostatin analogues (SSAs). Of these, 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy between January 2000 and July 2020. A propensity score–matching analysis included 111 patients in each group. The primary outcome measure was progression-free survival.
Key Findings
Median progression-free survival was 2.5 years (95% confidence interval [CI] = 2.3–3.0 years) in the PRRT group vs 0.7 years (95% CI = 0.5–1.0 years) in the chemotherapy/targeted therapy group among all patients (hazard ratio [HR] = 0.35, 95% CI = 0.28–0.44, P < .001]), and 2.2 years (95% CI = 1.8–2.8 years) vs 0.6 years (95% CI = 0.4–1.0 years) in the matched cohort (HR = 0.37, 95% CI = 0.27–0.51, P < .001).
Median overall survival was 12.0 years (95% CI = 10.7–14.1 years) vs 11.6 years (95% CI = 9.1–13.4 years) among all patients (HR = 0.81, 95% CI = 0.62–1.06, P = .11), and 12.2 years (95% CI = 9.1–14.2 years) vs 11.5 years (95% CI = 9.2–17.9 years) in the matched cohort (HR = 0.83, 95% CI = 0.56–1.24, P = .36).
On multivariate analysis, upfront PRRT was independently associated with improved progression-free survival (HR = 0.37, 95% CI = 0.26–0.51, P < .001). Hazard ratios adjusted for interaction of PRRT with other covariates were (all P < .001):
- 0.39 (95% CI = 0.27–0.57) for functioning and 0.29 (95% CI = 0.16–0.56) for nonfunctioning tumors
- 0.21 (95% CI = 0.12–0.34) for grade 1 and 0.52 (95% CI = 0.29–0.73) for grade 2 tumors
- 0.41 (95% CI = 0.24–0.61) for pancreatic and 0.19 (95% CI = 0.11–0.43) for intestinal site of tumor origin.
Adjusted hazard ratios were not significant for grade 3 tumors (0.31, 95% CI = 0.12–1.37, P = .13) or tumors with Ki67 proliferation index > 10% (0.73, 95% CI = 0.29–1.43, P = .31).
The investigators concluded, “In this cohort study, treatment with upfront PRRT in patients with enteropancreatic neuroendocrine tumors who had experienced disease progression with SSA treatment was associated with significantly improved survival outcomes compared with upfront chemotherapy or targeted therapy. Further research is needed to investigate the correct strategy, timing, and optimal specific sequence of these therapeutic options.”
Claudio Ricci, MD, of the Division of Pancreatic Surgery, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, University of Bologna, is the corresponding author for the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
