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EditorsEXECUTIVE EDITORSGregory Masters, MD, FACP, FASCO, Helen F. Graham Cancer CenterJyoti D. Patel, MD, Northwestern UniversitySPECIALTY EDITORSHoward H. Bailey, MD, University of Wisconsin Hospital and ClinicsMarcia S. Brose, MD, PhD, University of Pennsylvania Abramson Cancer CenterHarold Burstein, MD, PhD, FASCO, Dana Farber Cancer InstituteLisa Diller, MD, Dana Farber Cancer InstituteDon S. Dizon, MD, Massachusetts General HospitalHoward A. Fine, MD, New York University Langone Medical CenterGregory P. Kalemkerian, MD, University of Michigan Health SystemMark Moasser, MD, University of California San Francisco School of MedicineMichael N. Neuss, MD, Vanderbilt-Ingram Cancer CenterSteven J. O’Day, MD, Beverly Hills Health CenterOlatoyosi Odenike, MD, University of ChicagoCharles J. Ryan, MD, University of California San FranciscoGary K. Schwartz, MD, Columbia University Medical CenterAlan P. Venook, MD, University of California San FranciscoSandra L. Wong, MD, University of MichiganASCO PRESIDENTPeter Paul Yu, MD, FACP, FASCO, Palo Alto Medical FoundationASCO PRESIDENT-ELECTJulie M. Vose, MD, MBA, FASCO, University of Nebraska Medical CenterASCO CHIEF EXECUTIVE OFFICERAllen S. Lichter, MD, FASCOASCO CHIEF MEDICAL OFFICERRichard Schilsky, MD, FACP, FASCO


A Messagefrom the PresidentTen years ago, the American Society of Clinical Oncology (ASCO) first announced theyear’s biggest cancer research advances in the inaugural issue of Clinical Cancer Advances.Looking back at a decade of reports, it is exciting to see how transformative those yearshave been. Clinical Cancer Advances has documented the dawn of precision cancermedicine, the advent of effective new cancer prevention strategies, major improvements inthe management of treatment adverse effects, and many other critical advances.Although all research achievements in this annual report are important, it often seems that one rises above the rest,whether because of its tremendous impact on patient care, its pioneering science, or its cross-cutting significance. So, asClinical Cancer Advances enters its second decade, we are highlighting the year’s standout achievement with a new feature:ASCO’s Advance of the Year.For 2015, ASCO’s Advance of the Year is the transformation of treatment for chronic lymphocytic leukemia (CLL).CLL is the most common adult leukemia, and it disproportionately affects the elderly. Yet, until the past year, many olderpatients were without treatment options, because existing therapies caused severe, even life-threatening, adverse effects forthose who were frail or had other major health problems. But 2014 brought stunning new possibilities with the introduction offour new drugs that are both highly effective and far easier on patients. These therapies have filled a major unmet need forthose with newly diagnosed or resistant disease, making treatment—and remission—possible for more patients than ever.This advance also speaks to the importance of value in cancer care. Value is a major focus for ASCO, because clinical benefit,toxicity, and cost must all be factored into shared decision making to determine the best treatment options for patients. ASCOis working to develop a physician-guided tool that will help patients evaluate new treatment options such as those highlightedin this report.Another big change with this year’s report is that clinical research advances are ordered thematically, rather than by diseasearea. And within each thematic section, the report not only highlights recent advances, but identifies emerging trends as well.Clinical Cancer Advances also continues its emphasis on the unique and vital role of federally funded cancer research. In thisyear’s report, almost a third of the studies featured were supported by federal research dollars. One featured study revealedone of the biggest survival gains ever observed in men with advanced prostate cancer. Another found a simple, affordable newway to preserve fertility for women with early-stage breast cancer, while others helped deliver new therapies for hard-to-treatdiseases like brain cancer. For more than 40 years, the National Cancer Institute has funded many more clinical studies likethese, answering critical cancer care questions that might otherwise have been ignored.Despite these achievements, federal investment in research has stagnated over the past 10 years, resulting in a 23% loss inpurchasing power for the National Institutes of Health. In practical terms, this means promising research is going unfunded,new studies are being scaled back, fewer patients have the opportunity to participate in clinical trials, and future meaningfuladvances against cancer may be few and far between—unless our nation renews its commitment to fighting cancer.Advances in health information technology (IT)—including projects like ASCO’s CancerLinQTM—can help overcome someof these challenges. Such technologies will enable us to capture data and learn from every patient, ultimately helping makeclinical trials faster and smarter. But we cannot count on health IT alone.As with any major anniversary, we are reminded that history judges us by our achievements. In oncology, Clinical CancerAdvances documents a decade of remarkable research advances, with progress building on progress over time. Now is the timeto increase our nation’s investment to ensure we can build on these advances well into the future.Peter Paul Yu, MD, FACP, FASCOPresidentAmerican Society of Clinical Oncology2CLINICAL CANCER ADVANCES 2015

ExecutiveSummaryClinical cancer research has yielded tremendous gains,leading to longer survival and better quality of life for themore than half a million Americans diagnosed with thedisease each year. Great strides in cancer prevention havefurther decreased the burden of the disease. Cancer deathrates in the United States have declined 20% from theirpeak in 1991 (215.1 per 100,000 population) to 2010 (171.8 per100,000 population).1 Today, there are a record 14.5 millioncancer survivors alive in the United States.Now in its 10th year, the American Society of ClinicalOncology’s (ASCO’s) report, “Clinical Cancer Advances 2015:An Annual Report on Progress Against Cancer,” for thefirst time identifies ASCO’s Advance of the Year. Other newfeatures in this special anniversary issue include: A Decadein Review, which recounts the biggest changes in cancer caresince this report’s introduction; The 10-Year Horizon, whichpreviews trends likely to shape the next decade of cancercare; and a special series of research, which highlightsexciting new leads for treatment of rare cancers.In keeping with this report’s tradition, we explore theclinical advances of the prior year that stand to make thebiggest impact on improving cancer prevention, treatment,and care. The following is a summary of some of the mostexciting trends and developments.ADVANCE OF THE YEAR: GAINS IN THETREATMENT OF CHRONIC LYMPHOCYTICLEUKEMIAIn just over a year’s time, treatment for chronic lymphocyticleukemia (CLL), the most common form of adult leukemia,was transformed through the approval of four new therapyoptions. All the new treatments are easier to tolerate thanprior therapies, making treatment possible for more patientsthan ever—especially elderly patients who account for themajority of patients with CLL and had urgently needed new,less toxic options.For previously untreated patients who were unable totolerate the adverse effects of standard CLL treatments,the two different immunotherapy drugs, obinutuzumaband ofatumumab, given in combination with the standardchemotherapy chlorambucil, delay disease progression byroughly a year.And there is also good news for patients with previouslytreated CLL that has become resistant to standard treatmentor relapsed. New targeted drugs, ibrutinib and idelalisib,which block different molecular pathways that controlleukemia growth, are the first effective therapies for thesepatients. According to striking early clinical trial results,these drugs have the potential to transform CLL therapy,potentially eliminating the need for chemotherapy, theadverse effects of which are too difficult to bear for manyelderly patients with CLL.PRECISION MEDICINE RESEARCH BRINGS NEWTHERAPIES TARGETING IMMUNE SYSTEM ANDCANCER CELLSOnce a distant goal, precision medicine—an approachwhere treatments are matched to the genetic makeup ofthe patient and his or her tumor—is a common strategy formany patients with cancer today. Precision medicine allowsCLINICAL CANCER ADVANCES 20153

for better treatment outcomes and fewer adverse effectscompared with other approaches, such as chemotherapy.This new reality is the fruit of decades of dedicated researchon the biology of cancer.From January through October 2014, the US Food andDrug Administration (FDA) approved seven new drugs thattarget either cancer-driving proteins on the surface of orinside cancer cells or molecules on immune system cells(Table 1). Four new uses for previously approved drugs werealso approved. The new approvals bring hope for patientswith hard-to-treat types of melanoma and lung, stomach,blood, and cervical cancers.GENOMIC DISCOVERIES PROVIDE NEWLEADS FOR CANCER PREVENTION AND THERAPYModern high-throughput technologies provide extensivemolecular information on tumors, which is analyzed togain a deeper understanding of genetic factors that triggerand sustain cancer growth. This ever-growing knowledgeadvances patient care in many different ways—fromguiding day-to-day treatment decisions for individualpatients to steering the direction of new drug development.Two recent studies brought intriguing new insights, whichmay have implications for cancer prevention and therapy inthe future. In the first study, researchers were able to linkknown cancer triggers, such as tobacco and sun tanning, tospecific sets of genetic changes or mutational signatures intumor tissue. In another study, similar mutational signatureswere sometimes found in entirely different types of cancer.This finding suggests that treatment for a cancer is moredependent on mutations in a tumor than on the organ inwhich the cancer arises. For example, this may mean thatpatients with bladder cancer who have a specific mutationalTABLE 1. FDA APPROVALS OF ANTICANCER THERAPIES, JANUARY – OCTOBER 2014NEWLY APPROVED AGENTSGeneric NameTrade NameIndicationsDrug TargetDate of ApprovalOfatumumabArzerraIn combination with chlorambucil, for CD20previously untreated CLLApril 17, 2014RamucirumabCyramzaAdvanced gastric or GEJadenocarcinoma that cannotbe surgically removed or hasmetastasized after chemotherapyVEGF-R2April 21, 2014SiltuximabSylvantMCDIL-6April 23, 2014CeritinibZykadiaALK-positive, metastatic NSCLCALKApril 29, 2014BelinostatBeleodaqRelapsed or refractory PTCLHDACJuly 3, 2014IdelalisibZydeligRelapsed CLL, in combination withrituximabPI3KδJuly 23, 2014PembrolizumabKeytrudaUnresectable or metastaticmelanoma and disease progressionafter ipilimumab and, if BRAF V600mutation positive, progression aftera BRAF inhibitorPD-1September 4,2014NEW USES FOR EXISTING AGENTSGeneric NameTrade NameIndicationsDrug TargetDate of ApprovalTrametinib and dabrafenib incombinationMekinist andTafinlarUnresectable or metastaticmelanoma with a BRAF V600Eor V600K mutationMEK andBRAFJanuary 10, 2014IbrutinibImbruvicaCLLBTKFebruary 12, 2014MercaptopurinePurixanOral suspension for ALL as part ofa combination regimenn/aApril 28, 2014Bevacizumab for intravenousinfusionAvastinMetastatic cervical cancer, incombination with paclitaxel andcisplatin or paclitaxel and topotecanVEGFAugust 14, 2014Abbreviations: ALK, anaplastic lymphoma kinase; ALL, acute lymphoblastic leuk