Neuroendocrinology · 2022
Treatment Response and Clinical Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors to Lutetium-177-DOTATATE.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Raj Nitya, Coffman Kelley, Le Tiffany, Do Richard Kinh Gian, Rafailov Johnathan, Choi Ye, Chou Joanne F, Capanu Marinela, Dunphy Mark, Fox Josef J, Grewal Ravinder K, Reddy Ryan P, Riedl Christopher, Schoder Heiko, Bodei Lisa, Reidy-Lagunes Diane
Аннотация
INTRODUCTION: Lutetium-177 (177Lu)-DOTATATE received FDA approval in 2018 to treat somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs). Little data are available on response and outcomes for well-differentiated (WD) high-grade (HG) NETs treated with 177Lu-DOTATATE.
MATERIALS AND METHODS: Patients with WD HG NETs treated with 177Lu-DOTATATE at MSK from 2018 to 2020 were identified. Demographics, response (RECIST 1.1), and progression-free survival (PFS) were determined. Next-generation sequencing (NGS) was performed in the archival tumor.
RESULTS: Nineteen patients, all with progressive, heavily treated disease, were identified. Sites of tumor origin were: pancreas (74%), small bowel (11%), rectum (11%), and lung (5%); median Ki-67 was 32% (range 22-56). Thirteen patients (68%) completed all four 177Lu-DOTATATE cycles. Best response (N = 18 evaluable) was: 5/18 (28%) partial response, 8/18 (44%) stable disease, and 5/18 (28%) disease progression. Median PFS was 13.1 months (95% CI: 8.7-20.9). Most common treatment-related toxicities were thrombocytopenia (9 patients, 47%; G3/4, 1 patient, 5%), anemia (7 patients, 37%; G3/4, 2 patients, 11%), leukopenia (6 patients, 32%; G3/4, 0 patients), and liver function test elevation (4 patients, 21%; G3/4, 0 patients). NGS results were available from 13/19 tumors (68%). The most observed alterations were in MEN1 (6/13, 46%) and DAXX (4/13, 31%). No RB1 alterations identified.
CONCLUSION: We observed a meaningful disease control rate of 72% during treatment of WD HG NETs with 177Lu-DOTATATE. In this heavily pre-treated population, more than half of patients received all four treatment cycles with toxicities largely bone marrow-related. As would be expected in WD NETs, the vast majority had alterations in chromatin remodeling genes and no RB1 alterations.
MATERIALS AND METHODS: Patients with WD HG NETs treated with 177Lu-DOTATATE at MSK from 2018 to 2020 were identified. Demographics, response (RECIST 1.1), and progression-free survival (PFS) were determined. Next-generation sequencing (NGS) was performed in the archival tumor.
RESULTS: Nineteen patients, all with progressive, heavily treated disease, were identified. Sites of tumor origin were: pancreas (74%), small bowel (11%), rectum (11%), and lung (5%); median Ki-67 was 32% (range 22-56). Thirteen patients (68%) completed all four 177Lu-DOTATATE cycles. Best response (N = 18 evaluable) was: 5/18 (28%) partial response, 8/18 (44%) stable disease, and 5/18 (28%) disease progression. Median PFS was 13.1 months (95% CI: 8.7-20.9). Most common treatment-related toxicities were thrombocytopenia (9 patients, 47%; G3/4, 1 patient, 5%), anemia (7 patients, 37%; G3/4, 2 patients, 11%), leukopenia (6 patients, 32%; G3/4, 0 patients), and liver function test elevation (4 patients, 21%; G3/4, 0 patients). NGS results were available from 13/19 tumors (68%). The most observed alterations were in MEN1 (6/13, 46%) and DAXX (4/13, 31%). No RB1 alterations identified.
CONCLUSION: We observed a meaningful disease control rate of 72% during treatment of WD HG NETs with 177Lu-DOTATATE. In this heavily pre-treated population, more than half of patients received all four treatment cycles with toxicities largely bone marrow-related. As would be expected in WD NETs, the vast majority had alterations in chromatin remodeling genes and no RB1 alterations.