Impact of Using Corticosteroid Prophylaxis to Prevent Tumor Flare Reactions During 177Lu-DOTATATE Treatment in Patients with Neuroendocrine Tumors

TL;DR

This study examines whether corticosteroids can prevent tumor flare reactions in patients with neuroendocrine tumors undergoing Lu-DOTATATE treatment.

Contribution

The study evaluates the real-world efficacy of corticosteroid prophylaxis for tumor flare reactions in Lu-DOTATATE therapy.

Findings

28% of patients still experienced tumor flare reactions despite corticosteroid prophylaxis.

28% of patients experienced adverse effects from corticosteroids.

Corticosteroid prophylaxis did not significantly reduce tumor flare incidence compared to prior reports.

Abstract

177Lu-DOTATATE has changed the treatment landscape for patients with gastroenteropancreatic neuroendocrine tumors. As with all therapies, side effects are inevitable. For patients with a high burden of disease, treatment with 177Lu-DOTATATE can cause a tumor flare reaction, causing significant pain or other complications. There have been some reports on the use of corticosteroids to prevent this adverse effect. We aimed to see if we could achieve success at our institution when using corticosteroids to prevent a tumor flare reaction. We identified forty-six patients who receive corticosteroids in this setting. Twenty-eight percent of patients still had a tumor flare reaction with corticosteroid prophylaxis, and this statistic is similar to previously reported numbers. Twenty-eight percent of patients also experienced adverse effects from the corticosteroids used in this setting. Further studies are needed to examine the risks versus the benefits of corticosteroid use, so as to prevent tumor flare reactions in patients treated with 177Lu-DOTATATE with a high disease burden.

Background/Objectives: Since 177Lu-DOTATATE was approved for patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors (NETs), tumor flare reactions including increased pain and small bowel obstruction (SBO) have been reported. Retrospective reviews report some success in using corticosteroids for treatment and prophylaxis of tumor flare reactions from 177Lu-DOTATATE. Given that corticosteroids are used in practice to help prevent tumor flare reactions based on limited evidence, we aimed to assess if this practice was efficacious in our patient population. Methods: In this retrospective and single-institution study, we identified adult patients with NETs who were treated with 177Lu-DOTATATE between 1 October 2019 and 31 December 2024; these patients received corticosteroids as prophylaxis for flare reactions due to high burden of disease, significant peritoneal or mesenteric disease, or disease involvement of critical structures as determined by the treating provider. Variables including demographics, diagnosis, treatment history, steroid dosing, and outcomes were collected within a RedCAP database. Results: Forty-six patients were identified as having received corticosteroid prophylaxis to prevent a tumor flare reaction due to 177Lu-DOTATATE. Patients had a median age of 66, and 50% were female. The primary disease site was the small intestine (72%) followed by the pancreas (9%). The majority of patients had World Health Organization (WHO) grade 1 (41%) or WHO grade 2 (35%) diseases. Most patients (83%) received corticosteroids prior to the initiation of 177Lu-DOTATATE, while 17% of patients received corticosteroids due to having a previous tumor flare after 177Lu-DOTATATE administration. Despite corticosteroid prophylaxis, 28% of patients still experienced a tumor flare event, with three patients experiencing multiple tumor flare events. Small bowel obstructions occurred in 7% of patients and increased abdominal pain in 22% of patients. Adverse events (AEs) due to corticosteroids occurred in 28% of patients. Conclusions: Short-course corticosteroid prophylaxis to prevent tumor flare reactions in high-risk patients with neuroendocrine tumors treated with 177Lu-DOTATATE did not appear to decrease the incidence of tumor flare reactions compared to previously reported numbers. Randomized, placebo-controlled trials looking at the use of corticosteroids to prevent tumor flare reactions in patients treated with 177Lu-DOTATATE are needed to fully elucidate the safety and efficacy of corticosteroids used in this setting and to determine the impact on treatment outcomes.

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