Uncertainties in Regulatory Benefit-Risk Decision Making for Innovative Anticancer Therapies: Preliminary Results From a 2011-2024 Review of Extensions of Indications
Author(s)
Fábio Cardoso Borges, MPharm1, Luigi Lim, MSc1, Maria Manuel Teixeira, MSc1, Francesco Pignatti, MD2, Madeline Pe, PhD1, Caroline Voltz, MSc2, Denis Lacombe, MD1, Carla Torre, PhD3, Isabelle Huys, PhD4.
1European Organisation for Research and Treatment of Cancer, Brussels, Belgium, 2European Medicines Agency, Amsterdam, Netherlands, 3Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal, 4Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
1European Organisation for Research and Treatment of Cancer, Brussels, Belgium, 2European Medicines Agency, Amsterdam, Netherlands, 3Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal, 4Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
OBJECTIVES: The main objective is to characterise the uncertainties encountered by the European Medicines Agency (EMA) when initially assessing the benefit-risk of innovative anticancer medicines seeking an extension of indication (EoI). Additionally, we aim to identify product and pivotal clinical trial characteristics impacting uncertainty.
METHODS: In this retrospective review, we included anticancer medicines with EoI approvals following a positive EMA opinion between 2011-2024, identified via Committee for Medicinal Products for Human Use meeting highlights. Exclusions included paediatric indications, benign tumours, supportive therapies, and generic or hybrid products. Uncertainties were defined as text fragments in European Public Assessment Reports (EPARs)’s uncertainty sections describing concerns about favourable or unfavourable effects of the medicine and were counted and categorised using a recently proposed classification framework (doi: 10.1016/j.esmoop.2024.103991). Product and clinical trial characteristics were also extracted from EPARs, and their association with uncertainties will be analysed using count models.
RESULTS: These preliminary results are based on 101 EoI approved between 2021-2024. Of these, 92.1% received standard marketing authorisation, 12.9% had orphan designation, and 59.4% received EMA scientific advice. For 82.2%, the pivotal study was a randomised phase III trial, and the median sample size was 557 (IQR 300-886). The most common primary endpoints were progression-free survival (45.5%), overall survival (35.6%), and objective response rate (16.8%). A total of 405 uncertainties were identified, with a median of 4 per EoI (IQR 2-6). The most frequent efficacy-related uncertainties concerned effect size (n=116), efficacy in subpopulations (n=70), and relative efficacy (n=14). For safety, the most common uncertainties concerned safety in subpopulations (n=41), specific adverse events (n=33), and the general safety profile of the medicine (n=24).
CONCLUSIONS: This study provides insights into the uncertainty profile of benefit-risk assessments for recently approved oncology medicines seeking EoI. Full results, including associations with product/trial characteristics, will be presented at ISPOR Europe 2025.
METHODS: In this retrospective review, we included anticancer medicines with EoI approvals following a positive EMA opinion between 2011-2024, identified via Committee for Medicinal Products for Human Use meeting highlights. Exclusions included paediatric indications, benign tumours, supportive therapies, and generic or hybrid products. Uncertainties were defined as text fragments in European Public Assessment Reports (EPARs)’s uncertainty sections describing concerns about favourable or unfavourable effects of the medicine and were counted and categorised using a recently proposed classification framework (doi: 10.1016/j.esmoop.2024.103991). Product and clinical trial characteristics were also extracted from EPARs, and their association with uncertainties will be analysed using count models.
RESULTS: These preliminary results are based on 101 EoI approved between 2021-2024. Of these, 92.1% received standard marketing authorisation, 12.9% had orphan designation, and 59.4% received EMA scientific advice. For 82.2%, the pivotal study was a randomised phase III trial, and the median sample size was 557 (IQR 300-886). The most common primary endpoints were progression-free survival (45.5%), overall survival (35.6%), and objective response rate (16.8%). A total of 405 uncertainties were identified, with a median of 4 per EoI (IQR 2-6). The most frequent efficacy-related uncertainties concerned effect size (n=116), efficacy in subpopulations (n=70), and relative efficacy (n=14). For safety, the most common uncertainties concerned safety in subpopulations (n=41), specific adverse events (n=33), and the general safety profile of the medicine (n=24).
CONCLUSIONS: This study provides insights into the uncertainty profile of benefit-risk assessments for recently approved oncology medicines seeking EoI. Full results, including associations with product/trial characteristics, will be presented at ISPOR Europe 2025.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
HPR226
Topic
Health Policy & Regulatory
Topic Subcategory
Approval & Labeling
Disease
Oncology