Experience with 177Lu-Dotatate in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors at a Single Urban Cancer Center

Abstract

177Lu-Dotatate is an FDA approved peptide receptor radiotherapeutic (PRRT) agent for metastatic well differentiated midgut neuroendocrine tumors (NETs). Questions remain regarding tolerability in diverse subpopulations with higher grade disease, more than one prior line of treatment, and in non-ileal primaries. In this retrospective analysis, we review the outcomes of patients with histologically proven metastatic GEP-NETs who received 177Lu-Dotatate at a single racially diverse urban cancer center. Treated patients had disease that progressed on systemic therapy. Uptake at disease sites was demonstrated in all patients using 68-Gallium-Dotate PET/CT. ECOG performance score (PS) was 0 to 2. 177Lu-Dotatate was administered in 200 mCi doses every 8 weeks for a total of 4 cycles and a maximum of 800 mCi. Patients were followed with serial CT scan and/or abdominal MRI with best objective response assessed per RECIST criteria. Fifty-one patients were treated between December 2017 and September 2021. 42 patients completed a minimum 3-month follow-up imaging. Median age was 66 years, 59% were female, 66% identified as white, 26% as Black, 8% as other or chose not to specify. Most frequent primary site was small intestine (69%). All had metastatic disease involving the liver except for one. Median time from diagnosis to 177Lu-Dotatate was 51 months. Time from first line therapy to first 177Lu-Dotatate was 3.65 years CTCAE grade 3/4 hematologic toxicity was seen in 6 of 51 patients (12%) of patients. Grade 3/4 thrombocytopenia occurred in 3 pts, grade 3/4 leukopenia occurred in 2 pts and grade 3 anemia occurred in 1 patient. One patient developed myelodysplastic syndrome 1 year after first 177Lu-Dotatate. Patients who identified as non-white did not experience significantly higher rate of toxicity. Of the 42 patients who reached 3-month follow-up 29% had a partial response, 45% had a mixed or stable response, and 36% had progressive disease. Only gender demonstrated significant difference; with male gender associated with worse response categories (p = 0.001). Median overall survival (OS) was 2.13 years. Metastatic disease in the liver only (p = 0.013), tumor grade > 1 (p = 0.027), and no history of surgery (p = 0.011) were associated with significantly worse OS. The median progression free survival (PFS) was 1.56 years. Patients of male gender (p = 0.037), with liver only metastases (p = 0.013), and with higher grade tumors (p = 0.024) had worse PFS. There was no difference in PFS by race, primary tumor site (pancreatic vs small bowel), performance status, or prior treatment history. In this retrospective study, investigating a racially and socioeconomically diverse patients, we report similar toxicity to prior studies investigating 177Lu-Dotatate. Despite similar toxicity, median PFS and OS were inferior to reported outcomes in NETTER-1 which we suspect may be partly due to timing of treatment and differences in patient populations.