Thesis

Application of pharmacoepidemiological approaches to generate real-world evidence on the use and impact of metastatic colorectal cancer medicines

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Awarding institution
  • University of Strathclyde
Date of award
  • 2023
Thesis identifier
  • T16697
Person Identifier (Local)
  • 201976558
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Qualification Name
Department, School or Faculty
Abstract
  • Introduction: Metastatic colorectal cancer (mCRC) is characterised by multiple treatment strategies. Randomised clinical trials are not always aligned with clinical practice, and greater use of real-world (RW) studies has been suggested to inform health care decisions by providing results that reflect RW practice. Methods: This thesis utilised multiple methods. First, a systematic review and meta-analyses (SRMA) of RW studies including mCRC patients treated with first-line (1L) systemic anti-cancer therapy (SACT) was conducted to explore the comparative safety and effectiveness, including overall survival (OS), progression free survival (PFS) and objective response of 1L mCRC SACTs. Second, a retrospective observational cohort study using linkage of routinely collected data of mCRC patients treated with 1L SACT in NHS GGC from 01/01/2015 to 31/12/2016 was performed to investigate the factors influencing selection of 1L mCRC SACTs, treatment pathways, and treatment outcomes including median OS (mOS) and time-to-next-treatment (TTNT) of mCRC patients. Results: Between 2015 and 2016, A total of 220 new mCRC SACT users were identified in NHS GGC, with 52.3% (N=115) of the patients treated with a doublet of FOLFOX or FOLFIRI, 22.3% (N=49) with 5FU, 19.5% (N=43) with cetuximab+FOLFIRI, and 5% (N=11) of patients treated initially with aflibercept+FOLFIRI. Treatment choices for 1L mCRC were made based on patients’ age and gender, tumour RAS status, and previous treatment response. The median overall survival (mOS) for these patients was statistically influenced by the initial mCRC SACT and the performance status. The combination of cetuximab+FOLFIRI demonstrated a statistically significant prolonged mOS compared to 5FU (HR 0.4 (95% CI 0.24-0.85) and the longest time to next treatment (TTNT (12.93 months (95%CI 5.85-15.25)). The SRMA also indicated an OS, PFS, and overall response rate benefit for bevacizumab+chemotherapy over chemotherapy alone with a statistically increased risk of non-haematological toxicities and a non-statistically significant increased risk for haematological toxicity. Conclusions: Real-world evidence can help understand the impact of mCRC SACT on evidence-based practice.
Advisor / supervisor
  • Bennie, Marion
  • Kurdi, Amanj
Resource Type
DOI
Date Created
  • 2023

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