Outcomes with 177 lutetium-dotatate (177Lu-dotatate) in olfactory neuroblastoma (ONB): A case series.

Abstract

6108 Background: Olfactory neuroblastoma (ONB) is a rare malignant tumor of the nasal cavity with a high recurrence rate after local therapy. Effective treatments for recurrent/metastatic (R/M) ONB are lacking. ONB frequently expresses somatostatin receptor (SSTR). Radionuclide bound to somatostatin analogues is an established treatment for SSTR-expressing gastrointestinal and pancreatic neuroendocrine tumors. This study reports the efficacy and survival outcomes of ONB patients treated with 177Lu-dotatate at a comprehensive cancer center. Methods: We conducted a retrospective analysis of ONB patients treated with 177Lu-dotatate at MD Anderson Cancer Center through NOV 1 2024, with a follow-up cutoff date of DEC 1 2024. Time-to-event outcomes were estimated with the Kaplan-Meier method, and comparisons of survival were done with the log-rank test. Objective response rate (ORR) to 177Lu-dotatate was assessed by RECIST v1.1 and PERCIST criteria adapted to Ga-60 Dotatate PET-CT. The magnitude of effect was estimated with Cox proportional hazards model, with statistical significance set at p< 0.05. Results: Thirteen R/M ONB patients were identified, 8 were female, and the median age at first dose of 177Lu-dotatate was 54 years. Overall, 6 (46%) ONB tumors were Hyams grade 2, 5 (38%) were grade 2-3, 1 (8%) grade 3, and 1 (8%) grade 4. All patients had distant metastasis prior to 177Lu-dotatate treatment, with the most common sites being bone (76%), and dura (38%), while 6 (46%) also had locoregional disease. Six (46%) patients received 177Lu-dotatate as first line therapy, 4 (31%) as second line, and the remaining 3 (23%) in later lines. Prior therapies included somatostatin analogues (n=4), chemotherapy plus PD-L1 inhibitor (n=1), Lenvatinib (n=1), and clinical trials with experimental drugs (n=3). Among 10 patients with post-treatment restaging scans, PERCIST showed partial response in 7 (70%) and stable disease in 3 (30%). Of these pts, 7 were evaluable per RECIST, demonstrating partial responses in 4 (57%) and stable disease in 3 (43%). At a median follow-up of 19.8 months from starting 177Lu-dotatate, the median progression-free survival (PFS) was 17.43 mo. (95%CI 8.29-NE). For patients treated with 177Lu-dotate in second-line or beyond, the median PFS significantly shorter at 4.18 mo. (95%CI 1.35-NE); hazard ratio (HR) 0.22 (95%CI 0.08-0.60; p = 0.001). Median time-to-progression for 177Lu-dotatate was not achieved. There was no statistical difference in PFS between first or later lines 177Lu-dotatate use (HR 1.74; 95%CI 0.38-7.86; p = 0.47). Conclusions: 177Lu-dotate demonstrates activity in R/M ONB, with a favorable PFS compared to previously administered lines of systemic therapy. This case series, the largest reported to date to our knowledge, supports the growing evidence supporting for the use of 177Lu-dotate in this orphan disease.