Simulating Progression-Free and Overall Survival for First-Line Doublet Chemotherapy With or Without Bevacizumab in Meta
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ORIGINAL RESEARCH ARTICLE
Simulating Progression‑Free and Overall Survival for First‑Line Doublet Chemotherapy With or Without Bevacizumab in Metastatic Colorectal Cancer Patients Based on Real‑World Registry Data Koen Degeling1,2 · Hui‑Li Wong3,4 · Hendrik Koffijberg1 · Azim Jalali3 · Jeremy Shapiro5 · Suzanne Kosmider6 · Rachel Wong3,7,8 · Belinda Lee3,4,9 · Matthew Burge10 · Jeanne Tie3,4,6 · Desmond Yip11 · Louise Nott12 · Adnan Khattak13 · Stephanie Lim14 · Susan Caird15 · Peter Gibbs3,6 · Maarten IJzerman1,2,4
© Springer Nature Switzerland AG 2020
Abstract Background Simulation models utilizing real-world data have potential to optimize treatment sequencing strategies for specific patient subpopulations, including when conducting clinical trials is not feasible. We aimed to develop a simulation model to estimate progression-free survival (PFS) and overall survival for first-line doublet chemotherapy with or without bevacizumab for specific subgroups of metastatic colorectal cancer (mCRC) patients based on registry data. Methods Data from 867 patients were used to develop two survival models and one logistic regression model that populated a discrete event simulation (DES). Discrimination and calibration were used for internal validation of these models separately and predicted and observed medians and Kaplan–Meier plots were compared for the integrated DES. Bootstrapping was performed to correct for optimism in the internal validation and to generate correlated sets of model parameters for use in a probabilistic analysis to reflect parameter uncertainty. Results The survival models showed good calibration based on the regression slopes and modified Hosmer–Lemeshow statistics at 1 and 2 years, but not for short-term predictions at 0.5 years. Modified C-statistics indicated acceptable discrimination. The simulation estimated that median first-line PFS (95% confidence interval) of 219 (25%) patients could be improved from 175 days (156–199) to 269 days (246–294) if treatment would be targeted based on the highest expected PFS. Conclusions Extensive internal validation showed that DES accurately estimated the outcomes of treatment combination strategies for specific subpopulations, with outcomes suggesting treatment could be optimized. Although results based on real-world data are informative, they cannot replace randomized trials.
1 Introduction Clinical outcomes for metastatic colorectal cancer (mCRC) patients have improved substantially over the last 2 decades, partly due to increased efficacy of systemic treatment [1]. Initially, the availability of irinotecan and oxaliplatin made a major contribution to these improved outcomes [2–6]. Subsequently, the addition of bevacizumab, a vascular Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40273-020-00951-1) contains supplementary material, which is available to authorized users. Peter Gibbs and Maarten IJzerman contributed equally. * Koen Degeling [email protected] Extended autho
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