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Estimating adjuvant treatment effects in Stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real‐world data

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Title: Estimating adjuvant treatment effects in Stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real‐world data
Authors: Gabrielle Jongeneel, Thomas Klausch, Felice N. van Erning, Geraldine R. Vink, Miriam Koopman, Cornelis J.A. Punt, Marjolein J.E. Greuter, Veerle M.H. Coupé
Contributors: MS Medische Oncologie, Cancer
Source: Int J Cancer
Jongeneel, G, Klausch, T, van Erning, F N, Vink, G R, Koopman, M, Punt, C J A, Greuter, M J E & Coupé, V M H 2020, 'Estimating adjuvant treatment effects in Stage II colon cancer: Comparing the synthesis of randomized clinical trial data to real-world data', International Journal of Cancer, vol. 146, no. 11, pp. 2968-2978. https://doi.org/10.1002/ijc.32629
Publisher Information: Wiley, 2019.
Publication Year: 2019
Subject Terms: Male, Cancer Research, treatment effect, Organoplatinum Compounds, Leucovorin, Fluorouracil/therapeutic use, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Colonic Neoplasms/drug therapy, Organoplatinum Compounds/therapeutic use, Antineoplastic Combined Chemotherapy Protocols, Journal Article, Humans, Comparative Study, Neoplasm Staging, Netherlands, Randomized Controlled Trials as Topic, Leucovorin/therapeutic use, real-world data, Research Support, Non-U.S. Gov't, randomized clinical trial, 3. Good health, adjuvant chemotherapy, colon cancer, Oncology, Chemotherapy, Adjuvant, Colonic Neoplasms, Female, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Fluorouracil, Cancer Epidemiology, Chemotherapy, Adjuvant/methods
Description: There is an ongoing discussion regarding the impact of adjuvant chemotherapy in Stage II colon cancer. We therefore estimated adjuvant treatment effect in Stage II colon cancer using pooled disease‐free survival (DFS) data from randomized clinical trials (RCT approach) and compared this to real‐world data (RWD approach) estimates. First, we estimated the treatment effect in RCTs by (i) searching relevant trials reporting DFS data, (ii) generating patient‐level data from reported DFS data and (iii) estimating treatment effect in the patient‐level data. Second, the treatment effect was estimated in an observational cohort of 1,947 patients provided by the Netherlands Cancer Registry using three propensity score methods; matching, weighting and stratification. In the RCT approach, patient‐level data of 4,489 patients (events: 853) were generated from seven trials which compared two of the following treatment arms: control, 5FU/LV or FOLFOX. A Cox model was used to estimate a hazard ratio (HR) of 0.77 (0.43;1.10) for 5FU/LV vs. control and 0.93 (0.72;1.15) for FOLFOX vs. 5FU/LV. In the RWD approach, HRs for any adjuvant treatment vs. control were 0.95 (0.50;1.80), 0.88 (0.24;3.21) and 1.05 (0.04;2.06) using matching, weighting and stratification, respectively. There was no significant difference with the estimates from the RCT approach (interaction test, p > 0.10). The RCT data suggest a clinically relevant benefit of adjuvant chemotherapy in terms of DFS, but the estimate did not reach statistical significance. Stratified analyses are required to evaluate whether treatment effect differs in specific subgroups.
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1097-0215
0020-7136
DOI: 10.1002/ijc.32629
Access URL: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.32629
https://pubmed.ncbi.nlm.nih.gov/31424568
https://europepmc.org/abstract/MED/31424568
https://www.narcis.nl/publication/RecordID/oai%3Apure.atira.dk%3Apublications%2F1a7dcc03-5942-42d8-8f7c-9dcfb6f2071f
https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.32629
https://www.ncbi.nlm.nih.gov/pubmed/31424568
https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.32629
https://research.vumc.nl/en/publications/estimating-adjuvant-treatment-effects-in-stage-ii-colon-cancer-co
https://research.vumc.nl/en/publications/1a7dcc03-5942-42d8-8f7c-9dcfb6f2071f
https://dspace.library.uu.nl/handle/1874/441785
https://pure.amsterdamumc.nl/en/publications/165b2c6c-92a5-495b-9c48-1858a2358c11
https://doi.org/10.1002/ijc.32629
Rights: CC BY
Accession Number: edsair.doi.dedup.....7080c58559318684c169cb57edb77688
Database: OpenAIRE
Description
Abstract:There is an ongoing discussion regarding the impact of adjuvant chemotherapy in Stage II colon cancer. We therefore estimated adjuvant treatment effect in Stage II colon cancer using pooled disease‐free survival (DFS) data from randomized clinical trials (RCT approach) and compared this to real‐world data (RWD approach) estimates. First, we estimated the treatment effect in RCTs by (i) searching relevant trials reporting DFS data, (ii) generating patient‐level data from reported DFS data and (iii) estimating treatment effect in the patient‐level data. Second, the treatment effect was estimated in an observational cohort of 1,947 patients provided by the Netherlands Cancer Registry using three propensity score methods; matching, weighting and stratification. In the RCT approach, patient‐level data of 4,489 patients (events: 853) were generated from seven trials which compared two of the following treatment arms: control, 5FU/LV or FOLFOX. A Cox model was used to estimate a hazard ratio (HR) of 0.77 (0.43;1.10) for 5FU/LV vs. control and 0.93 (0.72;1.15) for FOLFOX vs. 5FU/LV. In the RWD approach, HRs for any adjuvant treatment vs. control were 0.95 (0.50;1.80), 0.88 (0.24;3.21) and 1.05 (0.04;2.06) using matching, weighting and stratification, respectively. There was no significant difference with the estimates from the RCT approach (interaction test, p > 0.10). The RCT data suggest a clinically relevant benefit of adjuvant chemotherapy in terms of DFS, but the estimate did not reach statistical significance. Stratified analyses are required to evaluate whether treatment effect differs in specific subgroups.
ISSN:10970215
00207136
DOI:10.1002/ijc.32629