A clinical score developed for patients with well-differentiated neuroendocrine tumors (NETs) who are being considered for peptide receptor radionuclide therapy (PRRT) with 177Lu-Dotatate appeared to predict progression-free survival (PFS) in patients with well-differentiated NETs treated with PRRT, but not other therapies.

The findings were presented by Satya B. Das, MD, the first author of the study, at the 2021 Gastrointestinal Cancers Symposium.

“As we all know, 177Lu-Dotatate has been a transformative treatment for patients with well differentiated NETS with progressive disease; however, multiple question remain about when to optimally sequence the therapy in relation to other available therapies and the patients who are ideal candidates for the therapy,” Das said.

In order to not only answer these questions but also categorize patients being considered for PRRT, Das and colleagues developed a clinical score at Vanderbilt Ingram Cancer Center (VICC) and tested its predictive capacity in 146 patients.


Continue Reading

Between March 1, 2016 and March 17, 2020, patients with progressive well-differentiated NETs under consideration for 177Lu-Dotatate were scored prospectively and retrospectively. The clinical score included 5 categories: available treatments for tumor type outside of 177Lu-Dotatate, prior systemic treatments, patient symptoms, tumor burden in critical organs, and presence of peritoneal carcinomatosis (PC). Each category was scored from 0 to 2 except for PC, which was scored from 0 to 1.

The primary outcome was PFS. Secondary end points included overall survival (OS), overall response rate, and development of grade 3 or 4 adverse events (AEs). Among the 146 patients included in the study, the primary tumor type represented was small bowel (81 patients) followed by pancreas (37 patients).

A multivariable Cox regression analysis that adjusted for tumor grade, primary tumor locations, PRRT doses received, and the interaction between PRRT doses received and clinical score was performed and showed a strong association between the number of PRRT doses received and clinical score, Das said. Patients with the longest PFS received 3 to 4 doses of PRRT and had clinical scores of less than 4. The analysis showed that among patients treated with 3 to 4 doses of 177Lu-Dotate (n=101), for each 2-point increase in the clinical score, the HR for PFS was 3.26 (95% CI, 2.05-5.19).

Patients with the poorest PFS received 1 to 2 doses of PRRT. Interestingly, in the cohort of patients who were considered for PRRT but did not receive it (n=31), there was no association between clinical score and PFS. Among patients not treated with PRRT, for each 2-point increase in clinical score, the HR for PFS was 1.37 (95% CI, 0.78-2.41).

The researchers did not see an association for OS based on the treatment modality received. For each 2-point increase in clinical score, the HR for OS was 2.25 (95% CI, 1.43-3.54). Das said that this was likely due to the limited number of deaths in the analysis (27 deaths) due to a short amount of follow-up after PRRT. 

In addition, Das said that it appeared that patients with lower clinical scores who received 177Lu-Dotatate saw a greater benefit from PRRT than patients with higher scores, which may influence how the treatment is sequenced. Specifically, this “suggests that sequencing 177Lu-Dotatate in earlier treatment lines may be more effective than sequencing 177Lu-Dotatate in later-line settings,” he added.

The most common grade 3 or 4 hematologic AE observed in patients receiving PRRT was lymphopenia (60 total events).

Das noted that the score has not yet been validated but is the first of its kind to be reported.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.

Reference

Das S, Du L, Schad A, et al. A clinical score (CS) for patients with well-differentiated neuroendocrine tumors (WD NETs) under consideration for peptide receptor radionuclide therapy (PRRT) with Lu 177-dotate. Poster presented at: Gastrointestinal Cancers Symposium; January 15-17, 2021. Abstract 363.

This article originally appeared on Cancer Therapy Advisor