Comparisons of treatment performance and therapy sequences in neuroendocrine neoplasms using progression-free...

Optimal sequencing of therapies is an important unresolved issue in metastatic neuroendocrine neoplasms (NEN). Progression-free survival (PFS) ratios constitute a potential method for intra-patient treatment comparisons and were used in this analysis to assess the relative treatment benefit of established therapies.

This retrospective study included NEN patients of the Medical University of Vienna (treated in 2010-2024) who had metastatic disease and had received ≥ 2 palliative systemic therapies. The primary objective was the calculation of PFS ratios for therapy sequences, with the PFS ratio defined as the proportion of PFS2 (subsequent treatment) and PFS1 (prior treatment).

Of the 177 patients included, 104 had neuroendocrine tumors (NET) G1/G2, 16 NET G3, 28 lung/thymic carcinoids, and 29 a neuroendocrine carcinoma (NEC). In terms of treatment sequence, SSA was the most common first-line treatment in NET G1/G2 and thoracic carcinoids (n = 84), frequently followed by PRRT (n = 60), everolimus (n = 13), and treatments grouped as 'other' (n = 9). After platinum/etoposide in NEC (n = 26), FOLFOX/FOLFIRI (n = 13), CAPTEM (n = 3), and 'other' therapies (n = 9) were second-line therapies. The median PFS ratio for PRRT after first-line SSA was 1.86, for everolimus 0.99, and for 'other' treatments 0.59 (p = 0.004). Following platinum/etoposide, FOLFOX/FOLFIRI had a median PFS ratio of 0.46. In subgroup analyses according to primary localization, everolimus led to disproportionately long PFS intervals following SSA/PRRT in lung/thymic carcinoids, whereas therapies after PRRT exhibited relatively low PFS ratios in enteropancreatic NET.

PFS ratios accommodate the heterogeneity of NEN and can provide insights regarding treatment performance and treatment sequencing.