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Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer








Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer


Benjamin K Schneider


Iowa State University






21 November 2019


Bevacizumab-pemetrexed/cisplatin combination therapy (BEV-PEM/CIS) is a first line therapeutic for non-small cell lung cancer (NSCLC). BEV-PEM/CIS has a narrow therapeutic window - the range of dosages which both reduce the size and spread of the cancer and do not lead to overdose or a damaging accumulation of side-effects. Those side-effects include damage to rapidly dividing healthy cells such as bone marrow and blood cell progenitors. For this reason, BEV-PEM/CIS dosages cannot be scaled to treat aggressive NSCLC. Recent literature suggests that administering bevacizumab and pemetrexed/cisplatin sequentially, rather than concurrently, would greatly improve the efficacy of the combination therapy without leading to additional side-effects. Unfortunately, the optimal gap between bevacizumab and pemetrexed/cisplatin administration in humans has not been determined.To address this need, we have previously developed a robust preclinical mathematical model of BEV-PEM/CIS, and we've used that mathematical model to make a first prediction of optimal BEV-PEM/CIS administration in humans. Mathematical modeling is an indispensable tool for scheduling optimization as it allows the researchers to simulate a large set of in-silico experiments and make practical predictions based on those experiments without the need for considerable time and resource investment in in-vivo studies. Those predictions can then be used to guide future studies, greatly accelerating drug development and optimization.To further refine our model, we kindly request access to previous clinical studies in BEV-PEM/CIS. With this data, we will be able to enhance our model to make better predictions in humans and provide a framework for any researcher working in a similar combination of drugs to make better, data-informed decisions. In addition, this model can be used as a starting point for developing individualized therapy recommendations for patients with NSCLC being treated with BEV-PEM/CIS.



[{ "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", "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": 2552, "Title": "ROCHE-AVF3752G", "Description": "A Phase II Trial of Bevacizumab in Combination With First- or Second-Line Therapy in Subjects With Treated Brain Metastases Due to Non-Squamous Non-Small Cell Lung Cancer" },{ "PostingID": 2556, "Title": "ROCHE-AVF0757G", "Description": "Effects of Two Doses of rhuMAB-VEGF Antibody in Combination w/Chemotherapy in Subjects With Locally Advanced or Metastatic Lung Cancer" },{ "PostingID": 2650, "Title": "LILLY-H3E-MC-JMHD", "Description": "PointBreak: a Randomized Phase III Study of Pemetrexed plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab versus Paclitaxel plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients with Stage IIIB or IV Nonsquamous Non-small Cell Lung Cancer" },{ "PostingID": 5061, "Title": "LILLY-H3E-EW-S125", "Description": "A Single-Arm, Phase 2 Trial of Pemetrexed, Cisplatin,and Bevacizumab as Induction, Followed by Pemetrexed and Bevacizumab as Maintenance, in First-Line Treatment of Nonsquamous Advanced NSCLC" },{ "PostingID": 14474, "Title": "ROCHE-ML21217", "Description": "Available - Avastin in Addition to Platinum-based Chemotherapy is Indicated for First-lime Treatment of Patients With Locally Advanced, Metastatic or Recurrent Non-small Lung Cancer Other Than Predominantly Squamous Cell Histology" },{ "PostingID": 14486, "Title": "ROCHE-YO25404", "Description": "A Study of Bevacizumab Versus Placebo in Combination With Carboplatin/Paclitaxel in Participants With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer Who Have Not Received Previous Chemotherapy" },{ "PostingID": 14487, "Title": "ROCHE-AVF3991n", "Description": "An Observational Study of Avastin (Bevacizumab) in Combination With Chemotherapy for Treatment of Metastatic or Locally Advanced and Unresectable Colorectal Cancer and Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Excluding Predominant Squamous Cell Histology)" }]

Statistical Analysis Plan