Neuroendocrine Tumor Clinical Score Estimates Benefit of Treatment

Researchers have developed a clinical score (CS) that represents the first validated clinical metric that can predict the anticipated benefit from peptide receptor radionuclide therapy (PRRT) in patients with well-differentiated neuroendocrine tumors (WD NETs), according to a study in JAMA Network Open.

The multicenter cohort study included an original cohort of 122 patients with WD NETs who were being considered for PRRT with lutetium-177 (¹⁷⁷Lu-dotatate from March 1, 2016, to March 17, 2020. The validation cohort included 126 patients with WD NETs from January 25, 2017, to March 6, 2020. The last follow-up date for survival assessment was December 16, 2020. Both cohorts were recruited from major cancer care centers.

All patients in the original cohort were assigned a CS prospectively while patients in the validation cohort were retrospectively assigned a CS by an investigator who was blinded to patient outcomes. Patients were analyzed based on a prognostic scoring system that included symptoms necessitating treatment, tumor bulk in critical organs, non-PRRT treatments available based on primary tumor origin, peritoneal carcinomatosis presence, and prior systemic therapy.

The primary outcome was progression-free survival (PFS), defined as the time from the initial ¹⁷⁷Lu-dotatate or other alternate treatment dose to the date of disease progression or death.

The validation cohort included 126 patients (64 male, median IQR aged 63.6 [52.9-70.7] years). Their median (IQR) CS was 3 (3-5) points, and their median (IQR) follow-up was 20.2 (12.4-27.2) months. On multivariable Cox regression from the validation cohort, for each 2-point increase in CS, the hazard ratio (HR) for PFS was 2.61 (95% CI, 1.64-4.16). For each 2-point increase in CS, the HR for overall survival (OS) was 3.89 (95% CI, 1.80-8.43).

The combined original and validation cohort included 248 patients (126 male, median (IQR) age 63.3 [53.3-70.3] years). Their median (IQR) CS was 4 (4-5) points, and their median (IQR) follow-up was 16.6 (9.3-23.5) months. A total of 152 patients had a CS ≤4 points, and 96 patients had a CS >4 points.

Multivariable Cox regression after adjustment for primary tumor site, tumor grade, and received PRRT doses showed that, for each 2-point increase in CS, the HR for PFS was 2.52 (95% CI, 1.89-3.36). No interaction was found between PRRT doses administered and CS. After adjustment for PRRT doses received, for each 2-point increase in CS, the HR for OS was 3.48 (95% CI, 2.33-5.18).

Among several study limitations, the investigators noted that although the original cohort patients underwent prospective CS assignment, the validation cohort patients underwent retrospective CS assignment. Also, the follow-up period from PRRT or alternative treatment initiation was relatively short and resulted in a limited number of deaths, which decreased the covariates they were able to include in the Cox regression model exploring the relationship between CS and OS. Furthermore, no conclusions can be made regarding the capacity of the CS to specifically predict PRRT response.

“Our study findings suggest that using ¹⁷⁷Lu-dotatate when patients are less pretreated and possess a lower degree of metastatic involvement may optimize treatment outcomes,” stated the researchers. “This notion, however, requires prospective confirmation from ongoing clinical trials.”

Disclosure: Some study authors declared affiliations with pharmaceutical and other private companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Das S, Chauhan A, Du L, et al. External validation of a clinical score for patients with neuroendocrine tumors under consideration for peptide receptor radionuclide therapy. JAMA Netw Open. 2022;5(1):e2144170. doi: 10.1001/jamanetworkopen.2021.44170