Systematic Literature Review (SLR) and Meta-Analysis (MA) of Clinical Outcomes for Second-Line and Higher (≥2L) Targeted Therapies for Advanced Colorectal Cancer (aCRC)
Author(s)
Amonkar M1, Frederickson AM2, Aksomaityte A3, Lang BM4, Zhang I5, Leconte P6, Adelberg DE7, Abderhalden LA8
1Merck & Co., Inc., Kenilworth, NJ, USA, 2Precision Xtract, Los Angeles, CA, USA, 3MSD (UK) Limited, London, UK, 4MSD, Flughafen, ZH, Switzerland, 5PRECISIONheor, San Francisco, CA, USA, 6MSD, Paris, France, 7Merck & Co, Inc., Kenilworth, NJ, USA, 8MSD, Zurich, Switzerland
Presentation Documents
OBJECTIVES: An SLR/MA was conducted to assess clinical outcomes for the current standard of care (SOC) therapies in a biomarker-unselected, aCRC population.
METHODS: The SLR was conducted using Embase, MEDLINE, and Cochrane (Jan. 2000 – Jul. 2021) and recent ASCO/ESMO conferences. Eligible studies included RCTs/controlled clinical trials/non-RCTs of any FDA/EMA licensed treatments among patients who had progressed on prior treatment (≥18 years age, ECOG 0 or 1). MA of objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were conducted among RCTs of relevant licensed and/or guideline recommended therapies for ≥2L aCRC (≥2L: FOLFOX/FOLFIRI +/-bevacizumab/ aflibercept/ ramucirumab/ cetuximab/ panitumumab, CAPEOX + bevacizumab; ≥3L: regorafenib, trifluridine/tipiracil). The ORR MA was performed using the Freeman-Tukey double arcsine transformation while MA of pooled survival curves for OS/PFS was conducted following Combescure et al. (2014) methodology.
RESULTS: Of 611 studies identified, 22 RCTs including 4,564 participants were analyzed in the MA of ORR. ORR ranged from 0.9% to 47.7%. Random effects pooled ORR estimate was 17.6% (95% CI: 12.6-23.2%). Median PFS (22 studies; 29 survival curves) was 6.1 months (5.5-7.0) with rates at 6, 12, and 24 months of 50.4%(44.3-57.4%), 20.3%(16.8-24.6%), and 2.4%(1.5-4.1%), respectively. Median PFS ranged from 2.0 to 21.4 months. Median OS (21 studies; 27 survival curves) was 13.3 months (11.8-14.7) with rates at 6, 12, and 24 months of 78.4%(74.2-82.8%), 55.3%(49.7-61.4%), and 23.3%(19.5-27.8%), respectively. Median OS ranged from 7.1 to 41.7 months. In analyses stratified by line of therapy, clinical outcomes were worse in patients who received later line treatment.
CONCLUSIONS: Standard treatments have demonstrated limited efficacy in previously-treated patients with biomarker-unselected aCRC, especially in later lines. Given that CRC is the 3rd most common cancer and 2nd leading cause of cancer mortality worldwide, a significant unmet medical need remains, that could be addressed by newer treatments under investigation.
Conference/Value in Health Info
Value in Health, Volume 25, Issue 12S (December 2022)
Code
CO110
Topic
Clinical Outcomes, Study Approaches
Topic Subcategory
Comparative Effectiveness or Efficacy, Literature Review & Synthesis, Meta-Analysis & Indirect Comparisons
Disease
SDC: Oncology