Transcript of "WSJ article:Personalized Cancer Therapies - wsj com"
Dow Jones Reprints: This copy is for your personal, non -commercial use only. To order presentation-ready copies for distribution to your colleagues, clients or customers, use the Order Reprints tool at the bottom of any article or visit www.djreprints.com See a sample reprint in PDF format. Order a reprint of this article nowHEALTH INDUSTRY JUNE 5, 2011Major Shift in War on CancerDrug Studies Focus on Genes of Individual Patients; Testing Obstacles LoomBy RON WINSLOW(See Correction & Amplification below .)CHICAGO—New research is signaling a major shift in how cancer drugs are developed and patients aretreated—offering the promise of personalized therapies that reach patients faster and are more effectivethan other medicines. At the heart of the change: an emerging ability for researchers to use genetic information to match drugs to the biological drivers of tumors in individuals. Studies released at the annual meeting of the American Society of Clinical Oncology here are helping to support previous findings that personalized medicine— introduced more than a decade ago—is closer to being realized as a weapon to fight cancer. "A pattern is developing at an accelerated pace where The Washington Post / Getty Images we are able to match genetic information about a tumor Studies show gains from targeting cancer patients more individually. Work at a breast-cancer clinical to a new agent and get results," says John Mendelsohn, trial at George Mason University. president of Houstons MD Anderson Cancer Center. Despite the progress, researchers stress, most Related Video personalized treatments dont necessarily offer a cure. More Evidence to Come in Cancer Debate Currently about 800 cancer drugs are in development, 6/1/2011 many of them designed to target specific mutations. It Traditional Prostate Test Doesnt Cut It may take changes in regulatory policy and the 12/22/2008 development of new diagnostic tests in order for 50% of Men Could Be Carriers of HPV successful therapies to come onto the market. Another 3/7/2011 1 issue is cost. The targeted drugs already available run into the tens of thousands a year.One study led by doctors at Memorial Sloan Kettering, for instance, found that among skin-cancerpatients with a mutation in a gene called BRAF, 48% responded to a targeted treatment, compared withjust 5% who responded to the current standard treatment.The report was published online Sunday by the New England Journal of Medicine. Another study, from
researchers at Massachusetts General Hospital, suggests that lung-cancer patients with a specificmutation lived significantly longer when treated with a targeted therapy from Pfizer Inc. than a matchedgroup of similar patients who didnt get the drug.Both drugs are now on a fast-track review at the U.S. Food and Drug Administration, reaching in theagency in about half the time it takes more conventional medicines to get there."Weve never had more insight into genetic pathways and the genetics of tumors than we do now," saysGary Gilliland, head of cancer research and development at Merck & Co. These insights are driving "anend-to-end change in the way we develop new drugs for cancer patients and the way we do business."By targeting mutations, researchers say fewer patients will be needed to prove the efficacy of new drugs,hastening their path to the market. In addition, fewer people will be enrolled in trials of drugs thatprovide them little hope of benefit.But the use in drug development of specific genetic traits in tumors, called biomarkers, poses a maze ofchallenges. Many tumors are complex organisms fueled by multiple pathways. When one is disruptedeven by a potent single agent, others compensate to help tumors develop resistance to treatment. Targettherapies will likely be more effective when given along with similar agents or as some are used now,with existing conventional drugs. Researchers and drug companies are already working to test combinations of targeted agents. In some cases, they are collaborating with rivals. Combining agents risks increasing side effects and the cost of therapy, researchers and regulators say, and will likely require changes to current procedures for approving drugs. In addition, companies developing any drug that targets a specific mutation must also develop a valid companion diagnostic test to identify patients who would be candidates for the treatment. Diagnostic tests are reviewed by part of the Food and Drug Administration that is separate from drug approval, complicating the need to develop the test and drug in tandem, says Mace Rothenberg, senior vice president of clinical development for Pfizers oncology business unit. Janet Woodcock, director of the FDAs Center for DrugEvaluation and Research, says the agency also sees the potential for targeted drugs and is working tochange regulatory policies to help accommodate these scientific advances. At a recent cancer symposiumin New York Dr. Woodcock said, "We are on the tipping point of a whole new game in how we developdrugs [for cancer]."The targeted skin-cancer drug featured at the ASCO meeting is called vemurafenib and is beingdeveloped by Roche Holding AG and Daiichi Sankyos Plexxikon unit. It inhibits a mutated form of agene called BRAF found in more than half of patients with advanced melanoma and has been shown tohave hardly any treatment effect on patients with a normal version of the gene.Data from a 675-patient trial showed that those taking the drug were 63% less likely to die over a six-month period compared to those taking chemotherapy called dacarbazine. The median time beforedisease progressed for patients on the drug was 5.3 months compared with 1.6 months onchemotherapy. As a side-effect, the drug caused a benign form of skin cancer in nearly one-fifth of
patients that researchers said was easily treated.The Pfizer drug reported on at the meeting is called crizotinib and it blocks a mutated gene called ALKthat is found in up to 7% of patients with a form of lung cancer called non-small-cell lung cancer. In thefirst report on survival rates benefit from the drug, Alice Shaw, a researcher at Massachusetts General,said 74% of 119 patients treated with the drug were alive after one year and 54% after two years. Thestudy wasnt randomized, but Dr. Shaw said survival for a comparable set of patients who werenttreated with crizotinib was 44% after one year and 12% after two years.Another report featured results from an initiative at MD Anderson Cancer Center involving severalexperimental drugs in initial, or phase I, testing. Typically, phase I studies of cancer drugs test a singleagent in patients to determine a maximum tolerable dose with the hope that a treatment effect might beseen in a couple of patients.The MD Anderson program pooled 1,144 patients in a phase I study after profiling their tumors formutations that might be targets of the tested drugs. Apostolia Tsimberidou, the researcher who led thestudy, reported that 40% had mutations in 10 molecular pathways that were targeted by theexperimental compounds.Tumors in 27% of those given agents that targeted their mutations responded to treatment compared to5% for those with unmatched therapies.Other researchers said such a high response rate in a phase I study was highly unusual and could helpprompt other academic and corporate researchers to change their protocols to help speed the early-phase trials.Such testing of patients is also moving into clinical practice thanks to plummeting costs of performingDNA sequencing that researchers use to identify patients mutations.Massachusetts General Hospital and MD Anderson Cancer Center are among institutions beginning tooffer routine genetic profiling of tumors for every patient, moving into clinical practice a strategyreserved only for research just a year or two ago and unheard of a decade ago.Write to Ron Winslow at firstname.lastname@example.orgCorrection & AmplificationDaiichi Sankyos Plexxikon unit is developing a targeted skin cancer drug with Roche Holding AG.Plexxikon was misspelled in a previous version of this story. Copyright 2011 Dow Jones & Company, Inc. All Rights Reserved This copy is for your personal, non-commercial use only. Distribution and use of this material are governed by our Subscriber Agreement and by copyright law. For non-personal use or to order multiple copies, please contact Dow Jones Reprints at 1-800- 843-0008 or visit www.djreprints.com