title: ALCHEMIST Trials: A Golden Opportunity to Transform Outcomes in Early-Stage Non-Small Cell Lung Cancer.
abstract: The treatment of patients with metastatic non-small cell lung cancer (NSCLC) is slowly evolving from empirical cytotoxic chemotherapy to personalized treatment based on specific molecular alterations. Despite this 10-year evolution, targeted therapies have not been studied adequately in patients with resected NSCLC who have clearly defined actionable mutations. The advent of next-generation sequencing has now made it possible to characterize genomic alterations in unprecedented detail. The efforts begun by The Cancer Genome Atlas project to understand the complexities of the genomic landscape of lung cancer will be supplemented further by studying a large number of tumor specimens. The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) is an NCI-sponsored national clinical trials network (NCTN) initiative to address the needs to refine therapy for early-stage NSCLC. This program will screen several thousand patients with operable lung adenocarcinoma to determine whether their tumors contain specific molecular alterations [epidermal growth factor receptor mutation (EGFR) and anaplastic lymphoma kinase rearrangement (ALK)], making them eligible for treatment trials that target these alterations. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively, after completion of their standard adjuvant therapy. ALCHEMIST will also contain a large discovery component that will provide an opportunity to incorporate genomic studies to fully understand the clonal architecture, clonal evolution, and mechanisms of resistance to therapy. In this review, we describe the concept, rationale, and outline of ALCHEMIST and the plan for genomic studies in patients with lung adenocarcinoma. Clin Cancer Res; 21(24); 5439-44. ©2015 AACR.
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri. rgovinda@dom.wustl.edu.
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Sumithra J
authors.initials: SJ
authors.lastname: Mandrekar
authors.affiliation: Division of Hematology and Oncology, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: David E
authors.initials: DE
authors.lastname: Gerber
authors.affiliation: Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Oxnard
authors.affiliation: Department of Biostatistics and Computational Biology, Harvard School of Public Health, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Dahlberg
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jamie
authors.initials: J
authors.lastname: Chaft
authors.affiliation: Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Shakun
authors.initials: S
authors.lastname: Malik
authors.affiliation: Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Margaret
authors.initials: M
authors.lastname: Mooney
authors.affiliation: Clinical Investigations Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Abrams
authors.affiliation: Lowe Center for Thoracic Oncology and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.affiliation: Division of Hematology and Oncology, UC Davis Comprehensive Cancer Center, Sacramento, California.
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Ramalingam
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, The University of Chicago, Chicago, Illinois. The University of Chicago Comprehensive Cancer Research Center, Chicago, Illinois.
authors.forename: Everett E
authors.initials: EE
authors.lastname: Vokes
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D015321:Gene Rearrangement; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D058990:Molecular Targeted Therapy; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D012107:Research Design
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases