EVALUATING THE FEASIBILITY OF INDIRECT TREATMENT COMPARISONS IN PATIENTS WITH EPNEC TREATED IN SECOND-LINE AND BEYOND (2L+): A GUIDELINE-INFORMED SYSTEMATIC LITERATURE REVIEW AND FEASIBILITY ASSESSMENT
Author(s)
Mairead McNamara, MBBCh, PhD1, Stephen Ijioma, MSc, PharmD2, Julijana Dukanovic, MSc2, Nicholas Liu, PharmD3, Franziska Engelking, PhD4, Daniela Zöller, PhD4, Mona Huhn, MSc5, Karolin Eberle, PhD5, Stefanie Wüstner, PhD5.
1Division of Cancer Sciences, University of Manchester & Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom, 2Boehringer Ingelheim, International GmbH, Ingelheim am Rhein, Germany, 3Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA, 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany, 5AMS Advanced Medical Services GmbH, Mannheim, Germany.
1Division of Cancer Sciences, University of Manchester & Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom, 2Boehringer Ingelheim, International GmbH, Ingelheim am Rhein, Germany, 3Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA, 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany, 5AMS Advanced Medical Services GmbH, Mannheim, Germany.
OBJECTIVES: Extrapulmonary neuroendocrine carcinoma (epNEC) is rare, aggressive and often diagnosed at an advanced stage, with no defined standard-of-care in 2L+. Indirect treatment comparisons (ITCs) may contextualize treatment effects in the absence of head to head trials. This study systematically reviewed evidence in 2L+ epNEC and assessed the feasibility of conducting methodologically sound ITCs.
METHODS: We searched for published treatment guidelines from 2020 onward, focusing on the USA, EU, UK, China, and Japan, to identify 2L+ epNEC therapies. Subsequently, a systematic registry search (ClinicalTrials.gov, EU CTR, CTIS) and literature review (Ovid MEDLINE, Cochrane CENTRAL) were conducted following JCA- and PRISMA-guidelines to identify studies evaluating these therapies. We characterized the evidence network and assessed ITC feasibility using predefined criteria.
RESULTS: The systematic search resulted in 19 included studies; 12 (63%) retrospective based on routine clinical data, 4 (21%) randomized non-comparative trials (median sample size 36 (range: 11-126)). Treatments were chemotherapy-based in 14 studies (74%), and 5 (26%) included checkpoint inhibitors. In 6 studies (32%), patient eligibility was restricted by tumor site (e.g., digestive NEC), 4 studies (21%) also included patients with pulmonary NEC. Baseline performance status, tumor response, and adverse events were not reported in 6 (32%), 3 (16%), and 3 (16%) studies for 2L+ epNEC, respectively. Of the studies reporting tumor response, 7 (44%) used outdated or unclear response assessment criteria. Regarding ITC feasibility, large methodological concerns arise due to network disconnect, population and outcome heterogeneity, small sample sizes, and lack of individual patient data (IPD).
CONCLUSIONS: The evidence for 2L+ epNEC treatment is sparse, consisting of small retrospective studies and few randomized trials, and is further limited by heterogeneity such as tumor site restrictions, inclusion of pulmonary NEC, and missing key baseline variables. Given the heterogeneity, fragmented evidence network and lack of IPD, robust interpretable ITCs are not currently feasible.
METHODS: We searched for published treatment guidelines from 2020 onward, focusing on the USA, EU, UK, China, and Japan, to identify 2L+ epNEC therapies. Subsequently, a systematic registry search (ClinicalTrials.gov, EU CTR, CTIS) and literature review (Ovid MEDLINE, Cochrane CENTRAL) were conducted following JCA- and PRISMA-guidelines to identify studies evaluating these therapies. We characterized the evidence network and assessed ITC feasibility using predefined criteria.
RESULTS: The systematic search resulted in 19 included studies; 12 (63%) retrospective based on routine clinical data, 4 (21%) randomized non-comparative trials (median sample size 36 (range: 11-126)). Treatments were chemotherapy-based in 14 studies (74%), and 5 (26%) included checkpoint inhibitors. In 6 studies (32%), patient eligibility was restricted by tumor site (e.g., digestive NEC), 4 studies (21%) also included patients with pulmonary NEC. Baseline performance status, tumor response, and adverse events were not reported in 6 (32%), 3 (16%), and 3 (16%) studies for 2L+ epNEC, respectively. Of the studies reporting tumor response, 7 (44%) used outdated or unclear response assessment criteria. Regarding ITC feasibility, large methodological concerns arise due to network disconnect, population and outcome heterogeneity, small sample sizes, and lack of individual patient data (IPD).
CONCLUSIONS: The evidence for 2L+ epNEC treatment is sparse, consisting of small retrospective studies and few randomized trials, and is further limited by heterogeneity such as tumor site restrictions, inclusion of pulmonary NEC, and missing key baseline variables. Given the heterogeneity, fragmented evidence network and lack of IPD, robust interpretable ITCs are not currently feasible.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
SA79
Topic
Health Technology Assessment, Study Approaches
Topic Subcategory
Literature Review & Synthesis, Meta-Analysis & Indirect Comparisons
Disease
Oncology, Rare & Orphan Diseases