Endocrine Abstracts

Background: Expected progression free survival (PFS) for patients with grade 3 well-differentiated neuroendocrine tumors treated with peptide receptor radionuclide therapy (PRRT) is approximately 9 months, and objective response rate (ORR) is 35%. Response rate to single agent immune checkpoint inhibitors for patients with G1-3 NET is ≤15%. Delivery of targeted radiation using PRRT may potentiate the anti-tumor immune response. The purpose of this study is to evaluate safety and efficacy of the combination of PRRT and PD1 inhibitor pembrolizumab in high-risk NET.

Methods: In a single arm prospective pilot study, adult patients with WHO grade 2 or 3 (Ki-67 index > 10%) metastatic NET of any primary site received concurrent pembrolizumab 200 mg every 3 weeks up to 35 doses and up to 4 doses of ¹⁷⁷Lu-DOTATATE PRRT (200mCi) at 8-week intervals. Treatment was terminated in the event of disease progression, performance status deterioration, and/or intolerable toxicity. Primary endpoint was best observed objective response rate (ORR) by RECIST v.1.1. Secondary endpoints were PFS and safety.

Results: A total of 26 patients were enrolled: 15 men, median age 60 years, median Ki-67 index 30% (range 11-70%), 6 patients with grade 2, 20 patients with grade 3 NET. Primary site: 15/26 pancreas, 6/26 small bowel, 3/26 lung, 2/26 other. As of August 15, 2024, 22/26 patients (84.6%) have been on study for at least 24 weeks, and 5/26 (19.2%) are still receiving pembrolizumab. Median follow-up was 13.7 mo. Grade 3 and 4 adverse events include anemia (n = 2, 7.7%), neutropenia (n = 2, 7.7%), and thrombocytopenia (n = 1, 3.8%) related to PRRT, and diabetes mellitus (n = 2, 7.7%) and hyponatremia (n = 3, 11.5%) attributable to pembrolizumab. In terms of best radiographic response, 9/26 patients (34.6%) demonstrated partial response, 16/26 (61.5%) had stable disease, and 2/26 (7.7%) had disease progression, with 23/26 (88.5%) patients having achieved some shrinkage of their disease (median 24.2%, range 4.3-84.1%). Median PFS was 11.2 months (95% CI 8.6, 14.4 months). Overall, 21 patients discontinued participation due to disease progression (n = 17), performance status deterioration (n = 2), or completion of planned two years of pembrolizumab treatment (n = 2). Updated safety, PFS, and ORR analyses will be reported.

Conclusions: In this pilot study of patients with well differentiated NET with Ki67>10%, combination treatment with ¹⁷⁷Lu-DOTATATE PRRT and pembrolizumab was well tolerated and associated with ORR 34.6% and mPFS 11.2 months. Additional research is needed to identify the patients most likely to benefit from combination therapy and to determine the incremental benefit of each component.

ABSTRACT ID28609