1161P - Progression-free survival ratio and the implications for treatment sequencing in neuroendocrine neoplasms

Background

Progression-free survival ratios (PFSr) have been used in phase II and precision oncology trials for treatment outcome evaluation and represent an intra-patient comparison of a therapeutic benefit. For neuroendocrine neoplasms (NEN), several treatment options are available, but the optimal treatment sequence is unknown. Here, we employed PFSr as a metric to assess relative tumor-stabilizing effects of various established therapies, which could potentially inform sequencing strategies.

Methods

In this retrospective study, metastatic NEN patients treated at the Medical University of Vienna 2010-2024 with two or more therapies were analyzed. The primary objective was to calculate PFSr (the ratio of PFS of two consecutive treatment lines) for therapy sequences and predefined subgroups. A PFSr of >1.3 was accepted as a disproportionately high relative treatment benefit.

Results

Out of 500 NEN patients, 177 had two or more palliative systemic treatments, 105 NET G1/2, 16 NET G3, 29 NEC, and 27 lung/thymic carcinoids. In total, 485 treatment lines were recorded, 114 peptide receptor radionuclide therapy (PRRT), 98 somatostatin analog (SSA), 59 everolimus (EVE), 44 capecitabine/temozolomide (CAPTEM), 44 platinum/etoposide (PE), 38 Re-PRRT, 22 FOLFOX/FOLFIRI (FF), and 66 other (OTH) therapies. In NET, first-line SSA was frequently followed by PRRT (n=60), EVE (13), and OTH (9). Sequences PE-FF (9), PE-CAPTEM (6), and PE-OTH (11) were common. Following SSA, PRRT elicited a high median PFSr of 1.86 (EVE 0.99 and OTH 0.59). Likewise, after PE, CAPTEM resulted in a median PFSr of 2.9, FF in 0.46, and OTH in 0.37. Overall, therapies after PRRT could not achieve a disproportionately long PFS. In lung/thymic carcinoids, PFSr were higher for EVE following SSA/PRRT than in other NET (1.2 versus 0.7 across all lines). There was no difference in overall survival (OS) from second line start based on the therapies following SSA (p=0.12) but a difference between therapies following PE (p=0.032).

Conclusions

This analysis of a large NEN cohort assessed the relative effectiveness of NEN treatments. PFSr could be an objective method to leverage retrospective data. Therapies identified as disproportionately effective could be used in earlier lines.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Raderer: Financial Interests, Personal, Invited Speaker: AbbVie, Gilead, Galapagos Pharma, Celgene, BMS, Ipsen, Novartis, Roche, Eisai, Eli Lilly. B. Kiesewetter-Wiederkehr: Financial Interests, Personal, Invited Speaker: Ipsen, Novartis, MSD, Advanced Accelerator Applications (AAA), Boehringer Ingelheim, Eli Lilly, BMS; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Ipsen, MSD, Daiichi Sankyo, BMS; Non-Financial Interests, Project Lead, Young Hematologist and Oncologists Group Austria (YHOGA): Austrian Society for Hematology and Medical Oncology (OeGHO). All other authors have declared no conflicts of interest.