RESEARCH ARTICLE
Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal Cell Carcinoma Witold Wiecek, Helene Karcher* LASER Analytica, Halton House, 20–23 Holborn, London, EC1N 2JD, United Kingdom * [email protected]
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Abstract
OPEN ACCESS Citation: Wiecek W, Karcher H (2016) Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal Cell Carcinoma. PLoS ONE 11(6): e0155389. doi:10.1371/journal.pone.0155389 Editor: Donald P Bottaro, National Institute of Health, UNITED STATES Received: March 23, 2016 Accepted: April 28, 2016 Published: June 6, 2016 Copyright: © 2016 Wiecek, Karcher. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data relating to source codes for all four models run in this study are available as supporting information. Funding: This study was funded by LASER Analytica. LASER Analytica has no commercial interests in any of the products studied. Members of the LASER Analytica network have no interest in a drug or other factors studied. Authors consult or currently participate in studies sponsored by virtually all pharmaceutical companies. The funder provided support in the form of salaries for authors HK and WW, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific
Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated with a firstline agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS) between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS) data digitized from the KaplanMeier curves reported in the studies. Three models allowing hazard ratios (HR) to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]). However, all models with time-varying HR showed better fits than the fixed-HR model. The loglogistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval
Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal Cell Carcinoma Witold Wiecek, Helene Karcher* LASER Analytica, Halton House, 20–23 Holborn, London, EC1N 2JD, United Kingdom * [email protected]
a11111
Abstract
OPEN ACCESS Citation: Wiecek W, Karcher H (2016) Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal Cell Carcinoma. PLoS ONE 11(6): e0155389. doi:10.1371/journal.pone.0155389 Editor: Donald P Bottaro, National Institute of Health, UNITED STATES Received: March 23, 2016 Accepted: April 28, 2016 Published: June 6, 2016 Copyright: © 2016 Wiecek, Karcher. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data relating to source codes for all four models run in this study are available as supporting information. Funding: This study was funded by LASER Analytica. LASER Analytica has no commercial interests in any of the products studied. Members of the LASER Analytica network have no interest in a drug or other factors studied. Authors consult or currently participate in studies sponsored by virtually all pharmaceutical companies. The funder provided support in the form of salaries for authors HK and WW, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific
Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom 1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated with a firstline agent relapse within 1 year and need second-line therapy. The present study aims to compare overall survival (OS) between nivolumab and cabozantinib from two recent pivotal studies comparing, respectively, each one of the two emerging treatments against everolimus in patients who relapse following first-line treatment. Comparison is traditionally carried out using the Bucher method, which assumes proportional hazard. Since OS curves intersected in one of the pivotal studies, models not assuming proportional hazards were also considered to refine the comparison. Four Bayesian parametric survival network meta-analysis models were implemented on overall survival (OS) data digitized from the KaplanMeier curves reported in the studies. Three models allowing hazard ratios (HR) to vary over time were assessed against a fixed-HR model. The Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09 (95% confidence interval: [0.77, 1.54]). However, all models with time-varying HR showed better fits than the fixed-HR model. The loglogistic model fitted the data best, exhibiting a HR for OS initially favoring cabozantinib, the trend inverting to favor nivolumab after month 5 (95% credible interval
