The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer

Papadimitrakopoulou, Vassiliki A.; Lee, John; Wistuba, Ignacio I.; Tsao, Anne S.; Fossella, Frank V.; Kalhor, Neda; Gupta, Sanjay; Byers, Lauren A.; Izzo, Julie; Gettinger, Scott; Goldberg, Sarah B.; Tang, Ximing; Miller, Vincent A.; Skoulidis, Ferdinandos; Gibbons, Don L.; Шен, Ли; Wei, Caimiao; Diao, Lixia; Peng, Sujuan; Wang, Jing; Tam, Alda L.; Coombes, Kevin R.; Koo, Ja Seok; Mauro, David; Rubin, Eric H.; Heymach, John V.; Hong, Waun Ki; Herbst, Roy S.

doi:10.1200/jco.2015.66.0084

Cited by 153 publications

(121 citation statements)

References 39 publications

(19 reference statements)

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“…In the BATTLE 2 study, about 200 lung cancer patients were enrolled on four treatment arms consisting of various combinations between the EGFR inhibitor erlotinib, the AKT inhibitor MK-2206, the MEK inhibitor AZD624, and the multi-kinase inhibitor sorafenib, with treatments based on EGFR and KRAS mutation status. Unfortunately, none of the four arms appeared more promising, and no significant biomarker-response relationships were revealed [5] . Similarly, the SHIVA study assessed off-label use of 11 available molecularly targeted agents (erlotinib, lapatinib plus trastuzumab, sorafenib, imatinib, dasatinib, vemurafenib, everolimus, abiraterone, letrozole, tamoxifen) for treating approximately 100 patients with multiple cancer types.…”

Section: Reviewmentioning

confidence: 99%

Many are better than one - Next Generation Multi-Variate Biomarkers for Precision Oncology

Kirouac²,

Schoeberl

2017

Can Cell Microenviron

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Existing companion diagnostics have helped to match drug treatments to patients. However, they are largely restricted to single-molecule, single-time-point measurements, which cannot capture the full dynamic complexity of cancer biology. The development of multivariate and even dynamic biomarkers for diagnostic assays could allow more patients to benefit from improved drug regimens. Here we describe our work which provides a case study of multivariate biomarkers where we integrated experimental data generated using multivariate profiling technologies with a variety of computational modeling and simulation methods to identify such biomarkers and make clinical predictions on their therapeutic utility. We believe this approach of integrating multivariate profiling technologies and computational models, and iterating between experimental discovery and model predictions, will be required to develop the next generation of multivariate diagnostics and realize the promise of precision medicine.

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Section: Reviewmentioning

confidence: 99%

Many are better than one - Next Generation Multi-Variate Biomarkers for Precision Oncology

Kirouac²,

Schoeberl

2017

Can Cell Microenviron

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“…Examples include the BATTLE trials (BATTLE-1 [1], BATTLE-2 [2]) and the National Clinical Trials Network (NCTN) supported Lung Master Protocol [3].…”

Section: Interviewmentioning

confidence: 99%

AURA3 Trial: Does Tagrisso (Osimertinib) have the Potential to Become the New Standard of Care for Second-Line Treatment of Patients with EGFR T790M Mutation-Positive Locally Advanced or Metastatic NSCLC

Papadimitrakopoulou

2016

Lung Cancer Manag.

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Vassiliki A Papadimitrakopoulou speaks to Roshaine Wijayatunga, Managing Commissioning Editor: Dr Papadimitrakopoulou is the Jay and Lori Eisenberg Distinguished Professor of Medicine and Chief of the section of Thoracic Medical Oncology in the Department of Thoracic/Head and Neck Medical Oncology at the University of Texas/MD Anderson Cancer Center. Her areas of expertise include design and development of novel therapeutic clinical trials for lung and head and neck neoplasms, personalized genomics-driven lung cancer therapy and translational research and cancer chemoprevention. Her extensive experience in design, development and implementation of translational research in the context of multidisciplinary research teams has led to research funding from National Cancer Institute (NCI), American Society of Clinical Oncology (ASCO) and Department of Defense (DOD) both independently and as a member of a research team in the Head and Neck SPORE program. Currently, she serves as the principal investigator and leads numerous clinical and translational research projects with a focus on the development of biomarker-based targeted therapy to overcome therapeutic resistance in advanced disease and immunotherapy. Most notably, she has led the multidisciplinary clinical and translational research infrastructure dedicated to the treatment of metastatic refractory NSCLC as part of the BATTLE-2 program, designed and developed the first-in-the-world comprehensive genomics-driven umbrella approach in Squamous Lung Cancer, the Lung Master protocol, jointly sponsored by NCI-Cancer Therapy Evaluation Program (CTEP) and Foundation for the National Institutes of Health (FNIH)/industry, aiming at bringing personalized medicine to patients with this disease. She is the Co-PI of an R01 award focusing on the role of KRAS mutations and targeting in lung cancer. She is the lead author or coauthor of over 150 published articles, book chapters and reviews, and numerous abstracts involving cancer therapeutics, prevention and translational research and she has received several awards including the ASCO Young Investigator and Career Development Award. On this R01 application, she will serve as Co-PI, working closely with Roy Herbst (Yale Cancer Center) and Don Gibbons (UT/MD Anderson Cancer Center), building on the recently completed BATTLE-2 program, and capitalizing on both laboratory findings supporting MEK targeted therapy and clinical effectiveness of immunotherapy and their combinations in addressing KRAS mutated lung cancer.

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“…4,5 The rapid development of targeted therapies is also resulting in more advanced and focused clinical trial designs whereby testing protocols aim to match patients whose tumors harbor specific somatic mutations with those specific therapies targeting the gene or pathway affected. 6,7 …”

mentioning

confidence: 99%

Somatic Mutation Analysis of Human Cancers: Challenges in Clinical Practice

Tsongalis

Coleman

2017

The Journal of Clinical Pharma

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Somatic mutation analysis of human cancers has become the standard of practice. Whether screening for single gene variants or sequencing hundreds of cancer-related genes, this genomic information is the basis for precision medicine initiatives in oncology. Genomic profiling results in information that allows oncologists to make a more educated selection of appropriate therapeutic strategies that more often combine traditional cytotoxic chemotherapy and radiation with novel targeted therapies. Here we discuss the nuances of implementing somatic mutation testing in a clinical setting. Keywordsclinical genomics, oncology, precision medicine, pharmacogenomics, somatic mutation Novel therapies, including the use of directed monoclonal antibodies, tyrosine kinase inhibitors, and immunotherapies, have come to fruition as our understanding of the etiology of human cancer expands. From the identification of the first oncogenes and tumor-suppressor genes to current full gene sequencing for the identification of somatic mutations, knowledge of tumor-cell genetic variant profiles has become critical to the management of the cancer patient.1-3 One projection of the Human Genome Project was to gain a more fundamental understanding of human disease at the genomic level such that novel therapeutics could be designed to provide a more personalized approach to disease management. The identification of numerous driver mutations in various human cancers, which are causally implicated in establishing growth advantages to a cell, have also become the target of novel therapies that confer more efficacious outcomes. 4,5 The rapid development of targeted therapies is also resulting in more advanced and focused clinical trial designs whereby testing protocols aim to match patients whose tumors harbor specific somatic mutations with those specific therapies targeting the gene or pathway affected. 6,7 Precision Medicine in OncologyWith respect to the cancer patient, the concept of targeted or individualized therapy can include 2 aspects of what is often termed pharmacogenomics. The first is the more traditional concept that encompasses how an individual may metabolize, absorb, transport, and excrete therapeutic drugs differently based on polymorphisms in the genes that code for these functions. This type of individual variation in metabolism was first described in 510 BC when Pythagoras recognized hemolytic anemia developing in some individuals who consumed fava beans.8 This phenotype was later attributed to a glucose-6-phosphate dehydrogenase deficiency. 9 We have termed pharmacogenomic concepts linked to drug metabolism PGX m , which corresponds to genetic variants that determine drug disposition, also referred to as drug pharmacokinetics.10,11 The conversion of a parent compound to an inactive metabolite or to one that is more easily excreted and the conversion of a prodrug to its active metabolite are examples of PGX m .PGX t is the second aspect of pharmacogenomics that involves the selection of a therapeutic drug based on the...

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The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer

Abstract: Despite improved progression-free survival on therapy that did not contain erlotinib for KRAS mut+ patients and improved prognosis for mesenchymal tumors, better biomarker-driven treatment strategies are still needed.

Cited by 153 publications

References 39 publications

Many are better than one - Next Generation Multi-Variate Biomarkers for Precision Oncology

Many are better than one - Next Generation Multi-Variate Biomarkers for Precision Oncology

AURA3 Trial: Does Tagrisso (Osimertinib) have the Potential to Become the New Standard of Care for Second-Line Treatment of Patients with EGFR T790M Mutation-Positive Locally Advanced or Metastatic NSCLC

Somatic Mutation Analysis of Human Cancers: Challenges in Clinical Practice

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