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Incorporating biomarkers into survival models to predict patient

Incorporating biomarkers into survival models to predict patient

Dr. Luigi Brunetti, PharmD, MPH

Rutgers University

23 November 2018

Lung cancer accounts for 28% of all cancer deaths, more deaths than any other cancer in the United States. One year survival in advanced non-small cell lung cancer (NSCLC) is less than 20%. While there have been advances in the treatment of lung cancer, many therapies provide only limited benefits in terms of survival. The influence of body composition has been evaluated in several studies, specifically, the influence of obesity on lung cancer survival. Outcomes have been mixed, with some studies demonstrating a paradoxical beneficial effect in early lung cancer where survival is improved in obese patients. However, many of these studies lacked data on relevant confounding variables, especially detailed information on previous cancer treatment. This confounder is especially important as it relates to drug dosing in the extremes of body weight. While there is a consensus statement supporting dosing strategy of conventional chemotherapy agents, protein therapeutics were excluded due to lack of available data. Extremes in body weight are likely in lung cancer as the estimated prevalence of overweight and obese individuals >20 years in the US is 154.7 million, and over 2 billion people are considered overweight or obese worldwide. On the side of the spectrum, cachexia is present in almost 60% of advanced lung cancer patients. Our clinical and preclinical preliminary data and other studies indicate that the current dosing paradigm in the extremes of body composition are inaccurate, which may contribute to suboptimal responses. The current proposal will focus on the monoclonal antibody (mAb) bevacizumab, an anti-vascular endothelial growth factor therapy. This agent was selected based on the frequency of use and evidence suggesting altered drug exposure in extreme body weights.

[{ "PostingID": 1307, "Title": "ROCHE-APM4074g", "Description": "A randomized, double-blind, phase ii trial of paclitaxel plus carboplatin plus bevacizumab with or without apomab in patients with previously untreated, advanced-stage non-small cell lung cancer" },{ "PostingID": 1314, "Title": "ROCHE-BO17704 (AVAIL)", "Description": "A randomized, double-blind multicenter 2-stage phase III study of bevacizumab in combination with cisplatin and gemcitabine versus placebo, cisplatin and gemcitabine in patients with advanced or recurrent non-squamous non-small cell lung cancer, who have not received prior chemotherapy" },{ "PostingID": 2548, "Title": "ROCHE-BO21015", "Description": "A Randomized, Open-label Study to Explore the Correlation of Biomarkers With Response Rate in Chemo-naive Patients With Advanced or Recurrent Non-squamous Non-small Cell Lung Cancer Who Receive Treatment With Avastin in Addition to Carboplatin-based Chemotherapy" },{ "PostingID": 2551, "Title": "ROCHE-ML21823", "Description": "An Open Label Study to Assess the Effect of Avastin (Bevacizumab) Combined With First Line Paclitaxel-carboplatin or Second Line Tarceva (Erlotinib) on Progression-free Survival in Non-squamous Non-small Cell Lung Cancer Patients With Asymptomatic Untreated Brain Metastasis" },{ "PostingID": 3848, "Title": "ROCHE-BO20571", "Description": "A randomized, open-label study comparing the anti-tumor effect of treatment with Tarceva plus Avastin versus chemotherapy plus Avastin in patients with advanced non-small cell lung cancer" }]

Statistical Analysis Plan