Somatostatin analogs in neuroendocrine tumors with Ki-67 index of ≥10

Somatostatin analogs (SSAs) are an established first-line therapy in intestinal and pancreatic neuroendocrine tumors (NETs). Based on Phase III studies, their use is recommended in NET with a Ki-67 index of up to 10%. The effect of first-line SSA therapy on differentiated NET with a Ki-67 index ≥10% is poorly understood. This study aimed to investigate the outcomes of SSA therapy in differentiated NETs with a Ki-67 index of ≥10%. A retrospective analysis of a prospectively created dataset of consecutive patients with NETs was performed. Patients with first-line SSA monotherapy in advanced NET with a Ki-67 index ≥10% were included. The study endpoints were progression-free survival (PFS), overall survival (OS), and clinical benefit rate, defined as partial remission (PR) or stable disease (SD). Of 362 consecutive patients with a Ki-67 index ≥10%, 67 received first-line SSA therapy. The Ki-67 index was 10-20% (G2) in 57 (85%) patients and >20% (G3) in 10 (15%). SD as the best response was reached in 40 (59.7%) patients and PR in 3 (4.5%), irrespective of the NET origin, time from the diagnosis, or somatostatin receptor-based tracer uptake. The median PFS was 18 (95% confidence interval [CI], 5.7-30.3) months, and the median OS was 60 (95% CI, 38.2-81.8) months after the initiation of SSA therapy. Median PFS was significantly longer in patients with a Ki-67 index of 10-20% (19 months; 95% CI, 6.2-31.8) compared to those with G3 NETs (6 months; 95% CI, 2.9-9.1; p = .015, log-rank test), and in patients with a liver tumor burden of ≤10% (24 months; 95% CI, 12.7-35.3) versus >10% (4 months; 95% CI, 2.3-5.7; p = .007). First-line SSA therapy can provide meaningful disease control in patients with G2 NETs and low tumor burden, despite a Ki-67 index ≥10%. It may be a reasonable alternative to more intensive therapies in selected patients.