title: Impact of Precision Medicine in Diverse Cancers: A Meta-Analysis of Phase II Clinical Trials.
abstract: OBJECTIVE
  The impact of a personalized cancer treatment strategy (ie, matching patients with drugs based on specific biomarkers) is still a matter of debate.
  
  
  METHODS
  We reviewed phase II single-agent studies (570 studies; 32,149 patients) published between January 1, 2010, and December 31, 2012 (PubMed search). Response rate (RR), progression-free survival (PFS), and overall survival (OS) were compared for arms that used a personalized strategy versus those that did not.
  
  
  RESULTS
  Multivariable analysis (both weighted multiple linear regression and random effects meta-regression) demonstrated that the personalized approach, compared with a nonpersonalized approach, consistently and independently correlated with higher median RR (31% v 10.5%, respectively; P < .001) and prolonged median PFS (5.9 v 2.7 months, respectively; P < .001) and OS (13.7 v 8.9 months, respectively; P < .001). Nonpersonalized targeted arms had poorer outcomes compared with either personalized targeted therapy or cytotoxics, with median RR of 4%, 30%, and 11.9%, respectively; median PFS of 2.6, 6.9, and 3.3 months, respectively (all P < .001); and median OS of 8.7, 15.9, and 9.4 months, respectively (all P < .05). Personalized arms using a genomic biomarker had higher median RR and prolonged median PFS and OS (all P ≤ .05) compared with personalized arms using a protein biomarker. A personalized strategy was associated with a lower treatment-related death rate than a nonpersonalized strategy (median, 1.5% v 2.3%, respectively; P < .001).
  
  
  CONCLUSIONS
  Comprehensive analysis of phase II, single-agent arms revealed that, across malignancies, a personalized strategy was an independent predictor of better outcomes and fewer toxic deaths. In addition, nonpersonalized targeted therapies were associated with significantly poorer outcomes than cytotoxic agents, which in turn were worse than personalized targeted therapy.
authors: Maria Schwaederle, Melissa Zhao, and Razelle Kurzrock, Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA; J. Jack Lee and John Mendelsohn, The University of Texas MD Anderson Cancer Center, Houston, TX; Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA; Alexander M. Eggermont and Vladimir Lazar, Institut Gustave Roussy, University Paris-Sud; and Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, and Razelle Kurzrock, Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France. mschwaederle@ucsd.edu.
authors: Maria
authors: M
authors: Schwaederle
authors: Maria Schwaederle, Melissa Zhao, and Razelle Kurzrock, Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA; J. Jack Lee and John Mendelsohn, The University of Texas MD Anderson Cancer Center, Houston, TX; Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA; Alexander M. Eggermont and Vladimir Lazar, Institut Gustave Roussy, University Paris-Sud; and Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, and Razelle Kurzrock, Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France.
authors: Melissa
authors: M
authors: Zhao
authors: Maria Schwaederle, Melissa Zhao, and Razelle Kurzrock, Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA; J. Jack Lee and John Mendelsohn, The University of Texas MD Anderson Cancer Center, Houston, TX; Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA; Alexander M. Eggermont and Vladimir Lazar, Institut Gustave Roussy, University Paris-Sud; and Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, and Razelle Kurzrock, Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France.
authors: J Jack
authors: JJ
authors: Lee
authors: Maria Schwaederle, Melissa Zhao, and Razelle Kurzrock, Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA; J. Jack Lee and John Mendelsohn, The University of Texas MD Anderson Cancer Center, Houston, TX; Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA; Alexander M. Eggermont and Vladimir Lazar, Institut Gustave Roussy, University Paris-Sud; and Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, and Razelle Kurzrock, Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France.
authors: Alexander M
authors: AM
authors: Eggermont
authors: Maria Schwaederle, Melissa Zhao, and Razelle Kurzrock, Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA; J. Jack Lee and John Mendelsohn, The University of Texas MD Anderson Cancer Center, Houston, TX; Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA; Alexander M. Eggermont and Vladimir Lazar, Institut Gustave Roussy, University Paris-Sud; and Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, and Razelle Kurzrock, Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France.
authors: Richard L
authors: RL
authors: Schilsky
authors: Maria Schwaederle, Melissa Zhao, and Razelle Kurzrock, Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA; J. Jack Lee and John Mendelsohn, The University of Texas MD Anderson Cancer Center, Houston, TX; Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA; Alexander M. Eggermont and Vladimir Lazar, Institut Gustave Roussy, University Paris-Sud; and Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, and Razelle Kurzrock, Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France.
authors: John
authors: J
authors: Mendelsohn
authors: Maria Schwaederle, Melissa Zhao, and Razelle Kurzrock, Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA; J. Jack Lee and John Mendelsohn, The University of Texas MD Anderson Cancer Center, Houston, TX; Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA; Alexander M. Eggermont and Vladimir Lazar, Institut Gustave Roussy, University Paris-Sud; and Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, and Razelle Kurzrock, Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France.
authors: Vladimir
authors: V
authors: Lazar
authors: Maria Schwaederle, Melissa Zhao, and Razelle Kurzrock, Center for Personalized Cancer Therapy, University of California, San Diego, Moores Cancer Center, La Jolla, CA; J. Jack Lee and John Mendelsohn, The University of Texas MD Anderson Cancer Center, Houston, TX; Richard L. Schilsky, American Society of Clinical Oncology, Alexandria, VA; Alexander M. Eggermont and Vladimir Lazar, Institut Gustave Roussy, University Paris-Sud; and Alexander M. Eggermont, Richard L. Schilsky, John Mendelsohn, Vladimir Lazar, and Razelle Kurzrock, Worldwide Innovative Network in Personalized Cancer Medicine, Villejuif, France.
authors: Razelle
authors: R
authors: Kurzrock
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D057285:Precision Medicine / Q000639:trends*
chemical_list: D000970:Antineoplastic Agents