V O L U M E 3 1 䡠 N U M B E R 1 䡠 J A N U A R Y 1 2 0 1 3
`
`JOURNAL OF CLINICAL ONCOLOGY
`
`A S C O S P E C I A L A R T I C L E
`
`Author affiliations appear at the end of
`this article.
`
`Published online ahead of print at
`www.jco.org on December 3, 2012.
`
`*Executive editor.
`
`†Specialty editor.
`
`Authors’ disclosures of potential con-
`flicts of interest and author contribu-
`tions are found at the end of this
`article.
`
`Corresponding author: Lada Krilov, PhD,
`American Society of Clinical Oncology,
`2318 Mill Rd, Suite 800, Alexandria, VA
`22314; e-mail: lada.krilov@asco.org.
`
`© 2012 by American Society of Clinical
`Oncology and the American Society of
`Hematology
`
`0732-183X/13/3101-131/$20.00
`
`DOI: 10.1200/JCO.2012.47.1938
`
`Clinical Cancer Advances 2012: Annual Report on
`Progress Against Cancer From the American Society of
`Clinical Oncology
`Bruce J. Roth,* Lada Krilov, Sylvia Adams,† Carol A. Aghajanian,† Peter Bach,† Fadi Braiteh,†
`Marcia S. Brose,† Lee M. Ellis,† Harry Erba,† Daniel J. George,† Mark R. Gilbert,† Joseph O. Jacobson,†
`Eric C. Larsen,† Stuart M. Lichtman,† Ann H. Partridge,† Jyoti D. Patel,† David I. Quinn,† Leslie L. Robison,†
`Jamie H. von Roenn,† Wolfram Samlowski,† Gary K. Schwartz,† and Nicholas J. Vogelzang*
`
`A MESSAGE FROM ASCO’S PRESIDENT
`
`I am delighted to present you with “Clinical Cancer Advances 2012: Annual Report on Progress Against
`Cancer From the American Society of Clinical Oncology.” The American Society of Clinical Oncology
`(ASCO) uses this opportunity each year to share the steady progress occurring in our understanding and
`treatment of cancer. For 2012, we offer again an inspiring perspective on clinical cancer advances over
`the past year, but with a cautionary note: if current threats to federal funding materialize, future progress
`in cancer research will be seriously undermined.
`Continued progress against cancer. As you read the following pages of this report, I hope you will share my
`unabashed enthusiasm—and pride—in how far we have come. To appreciate what this progress has meant to
`the millions of people who receive a cancer diagnosis each year, consider the following: (1) two of three people
`in the United States live at least 5 years after a cancer diagnosis (up from roughly one of two in the 1970s); (2) the
`nation’s cancer death rate has dropped 18% since the early 1990s, reversing decades of increases; and (3)
`individuals with cancer are increasingly able to live active, fulfilling lives because of better management
`of symptoms and treatments with fewer adverse effects.
`Importance of clinical cancer trials. These dramatic trends—and the advances highlighted in this
`report—would have been unthinkable without the engine that drives life-saving cancer treatment:
`clinical cancer research. Advances in technology and in our knowledge of how patient-specific molecular
`characteristics of the tumor and its environment fuel the growth of cancer have brought new hope to
`patients. Clinical trials are the key to translating cutting-edge laboratory discoveries into treatments that
`extend and improve the lives of those with cancer.
`But progress is only part of the story. Cancer remains a challenge, with many cancers undetected until
`their latest stages and others resisting most attempts at treatment. Tragically, cancer still kills more than
`500,000 people in the United States every year, and its global burden is growing rapidly.
`Bridges to better care. To conquer cancer, we need to build bridges to the future—bridges that will get
`scientific advances to the patient’s bedside quicker, bridges that will enable us to share information and
`learn what works in real time, and bridges that will improve care for all patients around the world.
`At ASCO, we recognize the unique role that oncologists must play. ASCO’s “Accelerating Progress
`Against Cancer: Blueprint for Transforming Clinical and Translational Cancer Research,”1 published last
`year, presents our vision and recommendations to make cancer research and patient care vastly more
`targeted, more efficient, and more effective. We have also launched a groundbreaking initiative,
`CancerLinQ, that aims to improve cancer care and speed research by drawing insights from the vast
`pool of data on patients in real-world settings.
`Renewing a national commitment to cancer research. We are on the threshold of major advances in cancer
`prevention, detection, and treatment—but only if, as a nation, we remain committed to this critical endeavor.
`The federally funded cancer research system is currently under threat by larger federal budget concerns.
`Clearly, Congress faces a complex budget environment, but now is not the time to retreat from our
`nation’s commitment to conquering a disease that affects nearly all of us. Bold action must be taken to
`ensure that we can take full advantage of today’s scientific and technologic opportunities.
`Please join me in celebrating our nation’s progress against cancer and in recommitting ourselves to
`supporting cancer research. Millions of lives depend on it.
`Sandra M. Swain, MD
`President
`American Society of Clinical Oncology
`
`J Clin Oncol 31:131-161. © 2012 by American Society of Clinical Oncology
`
`© 2012 by American Society of Clinical Oncology
`
`
`Downloaded from jco.ascopubs.org on July 21, 2014. For personal use only. No other uses without permission.Downloaded from jco.ascopubs.org on July 21, 2014. For personal use only. No other uses without permission.Downloaded from jco.ascopubs.org on July 21, 2014. For personal use only. No other uses without permission.
`
`
`Copyright © 2013 American Society of Clinical Oncology. All rights reserved.Copyright © 2013 American Society of Clinical Oncology. All rights reserved.Copyright © 2013 American Society of Clinical Oncology. All rights reserved.
`
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`Roth et al
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`EXECUTIVE SUMMARY
`
`Background
`Each year, the American Society of Clinical Oncology (ASCO)
`conducts an independent review of advances in clinical cancer re-
`search that have the greatest potential impact on patients’ lives. This
`year’s Report, “Clinical Cancer Advances 2012: Annual Report on
`Progress Against Cancer From the American Society of Clinical On-
`cology,” features 87 studies, 17 of which the Report’s editors have
`designated as major advances.
`Although cancer-related deaths have declined tremendously
`since the early 1990s, cancer remains a leading cause of death world-
`wide. An estimated 577,000 Americans will lose their lives to cancer in
`2012. The large number of advances featured in the Report affirms
`that clinical cancer research yields remarkable improvements in sur-
`vival and quality of life for patients with cancer. Many studies high-
`lighted this year capitalized on the growing knowledge about the
`complexity of cancer to develop sophisticated treatment approaches,
`such as combining targeted drugs for difficult-to-treat cancers and
`expanding the use of targeted drugs to multiple forms of cancer that
`share the same genetic alteration. Major advances over the past year
`were achieved in the areas of overcoming treatment resistance, per-
`sonalized medicine, and screening.
`It takes years of research effort to achieve advances that extend
`patients’ lives. This progress would not be possible without patient
`volunteers, dedicated investigators, and substantial public and private
`research investment. In the United States, the federally funded clinical
`
`Conquer Cancer Foundation
`
`(cid:127) The Conquer Cancer Foundation of the American
`Society of Clinical Oncology funded three studies
`featured is this year’s Report: molecular testing that
`identified new therapeutic targets in squamous cell
`lung cancer, a prospective trial that identified key
`factors affecting chemotherapy adverse effects in
`elderly patients, and a study showing promising
`activity of a new targeted drug in patients with a chem-
`otherapy-resistant form of sarcoma.
`
`(cid:127) The mission of the Conquer Cancer Foundation is to
`conquer cancer worldwide by funding breakthrough
`research and sharing cutting-edge knowledge. Over
`nearly 30 years, the Foundation’s Grants and Awards
`Program has provided more than $77 million in
`funding to support clinical and translational scientists
`at all levels of their careers, working around the globe.
`The grants reflect the commitment of the Foundation
`to address the full spectrum of oncology—focusing
`on every moment in which cancer touches people’s
`lives—from prevention to end-of-life care, for nearly
`every cancer type, and funding research in virtually all
`cancers, including rare ones.
`
`trials system is essential to progress against cancer. The Clinical Trials
`Cooperative Group program, sponsored by the National Cancer In-
`stitute (NCI), involves approximately 3,100 institutions and places
`more than 25,000 patients into large clinical trials of promising treat-
`ments each year. Many of the significant developments presented in
`this document were a direct result of clinical research conducted by
`these cooperative groups. Despite difficult economic times, preserving
`our nation’s investment in cancer research is absolutely necessary to
`keep the momentum that brings better treatments to the growing
`number of people with cancer.
`This year’s Report includes two new sections, Tumor Biology and
`Quality Cancer Care, which feature studies reflecting the rapid pace of
`progress in those specialized areas. The Report also highlights the
`year’s most important cancer policy developments and cancer care
`guidelines that are likely to influence cancer care over the com-
`ing years.
`
`Overcoming Treatment Resistance
`Some cancers, such as sarcoma, ovarian cancer, and neuroblas-
`toma, are notoriously difficult to treat, and many patients succumb to
`the disease shortly after diagnosis. A variety of factors contribute to
`treatment resistance. Some tumors are located in parts of the body that
`may not be readily accessible to some drugs. Tumors acquire genomic
`changes, some of which enable them to evade or counter the effects of
`the treatment. Research results reported this year demonstrate how
`our understanding of the complex biology of cancer is leading the way
`to overcoming treatment resistance.
`A potentially useful strategy for conquering resistant tumors is to
`attack more than one target in a molecular pathway that is critical for
`tumor survival and growth. This can be achieved through use of
`multitargeted drugs, such as the new agents regorafenib, which has
`benefited patients with treatment-resistant GI stromal
`tumors
`(GISTs) and metastatic colorectal cancer; crizotinib, which has shown
`promising activity against neuroblastoma and anaplastic large-cell
`lymphoma (ALCL) in children; and cabozantinib, which seems to
`slow progression of medullary thyroid carcinoma. An alternative
`approach is to treat patients with two or more drugs that target the
`same pathway. There were three reports of improved outcomes for
`patients with breast cancer using such a strategy (combining two
`anti– human epidermal growth factor receptor 2 [HER2] agents
`and combining an aromatase inhibitor with a mammalian target of
`rapamycin [mTOR] inhibitor) this year. Early trial results showed
`that combining drugs that target mTOR and insulin-like growth
`factor receptor (IGF-R) delays progression of metastatic sarcoma
`resistant to standard treatments.
`In addition, novel targeted agents in the class of drugs known as
`tyrosine kinase inhibitors (TKIs) showed promising activity against
`treatment-resistant forms of leukemia (ponatinib and ibrutinib), soft
`tissue sarcoma (pazopanib), and breast cancer (lapatinib).
`
`No Two Tumors Are the Same: The Promise of
`Precision Medicine
`Oncology is rapidly transitioning to an era of precision medicine,
`where patients receive treatments tailored to the genetic makeup and
`biology of their tumors. Just as no two patients are the same, it is
`becoming increasingly clear that no two tumors are exactly the same.
`In some situations, the genetic variations are not critical to the behav-
`ior of a tumor, but in others, these variations may guide specific
`
`132
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`JOURNAL OF CLINICAL ONCOLOGY
`© 2012 by American Society of Clinical Oncology
`Downloaded from jco.ascopubs.org on July 21, 2014. For personal use only. No other uses without permission.
`Copyright © 2013 American Society of Clinical Oncology. All rights reserved.
`
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`Clinical Cancer Advances 2012
`
`treatment approaches. This year, an important study revealed that
`there are also dramatic variations in the genomic landscape within a
`single tumor and among primary and distant tumors (metastases) in
`the same patient. Researchers now know that even subtle genetic
`differences can make one tumor responsive and another resistant to
`the same drug.
`Two large-scale genomic profiling studies captured genomic
`snapshots of more than 1,000 different cancer cell lines, representing
`much of the tissue-type and genetic diversities of human cancers, and
`assessed how each of them responded to dozens of different anticancer
`drugs. This information will enhance rational drug development and
`speed the discovery of new personalized treatments. New results stem-
`ming from The Cancer Genome Project identify potential new drug
`targets in colorectal cancer, reveal that epigenetic regulation is critical
`for cancer cell survival, and propose innovative technologies for pre-
`dicting chemotherapy response in patients with ovarian cancer. Sev-
`
`eral other studies featured in the Report address the need to identify
`treatment-resistant patients early, so they can be directed to alterna-
`tive, potentially effective treatments while being spared the adverse
`effects of regimens that are not likely to benefit them.
`
`New Insights Into Risks and Benefits of
`Cancer Screening
`It is estimated that approximately one third of all cancer cases
`could be prevented. The main opportunities for cancer preven-
`tion include lifestyle and dietary changes and early detection
`through screening.
`Although routine screening has dramatically reduced the inci-
`dence and death rates for some cancers, such as cervical cancer, the
`value of screening for many other cancers remains uncertain. In fact,
`in some instances, risks of screening, such as false-positive findings
`
`Generic Name
`
`Trade Name
`
`Manufacturer
`
`Indications
`
`Date of Approval
`
`Table 1. FDA Approvals of Anticancer Agents, October 2011 to October 2012
`
`Newly approved
`agents
`Axitinib
`
`Inlyta
`
`Pfizer, New York, NY
`
`Vismodegib
`
`Erivedge
`
`Genentech, South San
`Francisco, CA
`
`Pertuzumab
`
`Perjeta
`
`Genentech
`
`Carfilzomib
`
`Kyprolis
`
`Onyx Pharmaecuticals, South
`San Francisco, CA
`
`Ziv-aflibercept
`
`Zaltrap
`
`sanofi-aventis, Bridgewater, NJ;
`Regeneron Pharmaceuticals,
`Tarrytown, NY
`
`Enzalutamide
`
`Xtandi
`
`Medivation, San Francisco, CA
`
`Regorafenib
`
`Stivarga
`
`Bayer HealthCare
`Pharmaceuticals, Wayne, NJ
`
`Expanded indications
`for existing
`agents
`Imatinib mesylate
`
`Pazopanib
`
`Cetuximab
`
`Gleevec
`
`Novartis, Basel, Switzerland
`
`Votrient
`
`Erbitux
`
`GlaxoSmithKline, Brentford,
`United Kingdom
`ImClone Systems, Bridgewater,
`NJ
`
`Everolimus
`
`Afinitor
`
`Novartis
`
`Vincristine sulfate
`liposome
`injection
`
`Marqibo
`
`Talon Therapeutics, South San
`Francisco, CA
`
`For treatment of patients with advanced kidney cancer
`(renal cell carcinoma) who have not responded to
`other treatments for this type of cancer
`For use in patients with locally advanced basal cell
`cancer who are not candidates for surgery or
`irradiation and for patients whose cancer has
`metastasized
`For use in combination with trastuzumab and
`docetaxel as first-line treatment for patients with
`HER2-positive metastatic breast cancer
`For treatment of patients with multiple myeloma
`whose disease has progressed despite at least two
`prior therapies, including bortezomib and an
`immunomodulatory agent
`For use in combination with FOLFIRI for treatment of
`patients with metastatic colorectal cancer that is
`resistant to or has progressed after an oxaliplatin-
`containing regimen
`For treatment of patients with metastatic castration-
`resistant prostate cancer who have previously
`received docetaxel
`For treatment of patients with metastatic colorectal
`cancer that has progressed despite standard
`treatments
`
`January 27, 2012
`
`January 30, 2012
`
`June 8, 2012
`
`July 20, 2012
`
`August 3, 2012
`
`August 31, 2012
`
`September 27, 2012
`
`For adjuvant treatment of adult patients after complete
`gross resection of Kit (CD117) –positive GISTs
`For treatment of patients with advanced soft tissue
`sarcoma who have received prior chemotherapy
`For use in combination with FOLFIRI chemotherapy
`for first-line treatment of patients with KRAS
`mutation–negative, EGFR-expressing metastatic
`colorectal cancer
`For use in combination with exemestane to treat
`certain postmenopausal women with advanced
`hormone-receptor positive, HER2-negative breast
`cancer
`For treatment of adult patients with Ph-negative acute
`lymphocytic leukemia in ⱖ second relapse or
`whose disease has progressed after ⱖ two
`antileukemia therapies
`
`January 31, 2012
`
`April 26, 2012
`
`July 6, 2012
`
`July 20, 2012
`
`August 9, 2012
`
`Abbreviations: EGFR, epidermal growth factor receptor; FDA, US Food and Drug Administration; FOLFIRI, fluorouracil, leucovorin, and irinotecan; GIST, GI stromal
`tumor; HER2, human epidermal growth factor receptor 2; Ph, Philadelphia chromosome.
`
`www.jco.org
`
`© 2012 by American Society of Clinical Oncology
`Downloaded from jco.ascopubs.org on July 21, 2014. For personal use only. No other uses without permission.
`Copyright © 2013 American Society of Clinical Oncology. All rights reserved.
`
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`leading to unnecessary treatments, have been shown to be greater than
`potential benefits.
`For example, this year, a study found that flexible sigmoidoscopy,
`a technique used to examine the rectum and lower part of the bowel,
`reduces colorectal cancer incidence and death rates. These findings
`support wider use of flexible sigmoidoscopy in colorectal cancer
`screening, but more research is needed to determine how its perfor-
`mance compares with that of colonoscopy. On the other hand, an-
`other large study showed that yearly chest x-ray examinations do not
`reduce lung cancer death rates in the general population.
`
`New Drug Approvals
`Between October 2011 and October 2012, on the basis of encour-
`aging results from large clinical trials, the US Food and Drug Admin-
`istration (FDA) approved seven new anticancer drugs and expanded
`indications for five existing agents (Table 1) to provide new treatment
`options for patients with certain forms of myeloma (carfilzomib),
`leukemia (liposomal vincristine), breast cancer (pertuzumab and
`everolimus), skin cancer (vismodegib), prostate cancer (enzalut-
`amide), GISTs (imatinib mesylate), colorectal cancer (cetuximab, ziv-
`aflibercept, and regorafenib), kidney cancer (axitinib), and soft tissue
`sarcoma (pazopanib).
`Almost all of the newly approved drugs are targeted agents,
`meaning that they are designed to block the activity of specific proteins
`involved in tumor growth. One agent, vismodegib, marks the first
`FDA approval of a drug that targets the hedgehog signaling pathway,
`which plays an important role in tissue growth and repair. The drug is
`also being tested in clinical trials for colorectal, stomach, and pancre-
`atic cancers.
`
`About Clinical Cancer Advances
`ASCO developed this Annual Report, now in its eighth year, to
`document the important progress being made in clinical cancer re-
`search and to highlight emerging trends in the field. The Report serves
`to outline to the public progress achieved against cancer by reviewing
`the major advances in clinical cancer research and care each year.
`This report was developed under the direction of a 21-person
`editorial board composed of prominent oncologists with expertise in
`areas pertinent to each section of the Report. The editors reviewed
`research published in peer-reviewed scientific or medical journals and
`presented at major scientific meetings over a 1-year period (October
`2011 to September 2012).
`The advances included in this Report are categorized as major
`and notable. Major advances are considered practice changing and
`had to have been published in a peer-reviewed journal and/or report
`on a treatment that received FDA approval in the past year. Notable
`advances are promising clinical research results that are not immedi-
`ately applicable to practice, either because a drug is not yet FDA
`approved or because the information is only available in abstract form
`(ie, has not yet appeared in a peer-reviewed publication).
`The research reviewed in this Report covers the full range of
`clinical research disciplines: epidemiology, prevention, screening,
`early detection, treatment (including surgery, chemotherapy, radia-
`tion, targeted therapy, immunotherapy, and personalized therapy),
`patient and survivor care (including end-of-life care and elderly pa-
`tient care), biomarkers, tumor biology, and cancer disparities.
`This Report is intended for anyone with an interest in cancer care,
`including the general public, news media, patients, caregivers, oncol-
`
`ogists and other medical professionals, policymakers, and cancer ad-
`vocacy organizations.
`
`About ASCO
`ASCO is the world’s leading professional organization represent-
`ing physicians who care for people with cancer. With more than
`30,000 members, ASCO is committed to improving cancer care
`through scientific meetings, educational programs, and peer-
`reviewed journals. For ASCO information and resources, visit
`http://www.asco.org. Cancer information for the lay public is
`available at http://www.cancer.net.
`
`BLOOD AND LYMPHATIC CANCERS
`
`Cancers of the blood and lymphatic system include leukemia, lym-
`phoma, and multiple myeloma. The most common blood cancer,
`leukemia, includes several distinct diseases: acute lymphocytic leuke-
`mia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous
`leukemia (AML), and chronic myelogenous leukemia (CML).
`This year, investigators reported encouraging results in clinical
`trials that tested new chemotherapies, targeted drugs, antibodies, and
`antibody-drug combinations. One trial resurrected interest in a previ-
`ously withdrawn AML drug, proposing a new dosing scheme that
`seems safer for patients yet still effective. Long-term results of a large
`trial confirmed that an antibody-chemotherapy drug combination
`is more effective and better tolerated than the standard antibody-
`chemotherapy combination in mantle-cell and indolent lymphomas.
`And finally, results of three early-phase trials point to promising new
`therapies for treatment-resistant CML, ALL, and CLL.
`
`Major Advances
`Lenalidomide maintenance therapy delays multiple myeloma re-
`lapse after stem-cell transplantation. Since the introduction of high-
`dose chemotherapy, outcomes have improved considerably for
`patients with multiple myeloma. However, in most of those patients,
`
`ASCO’s CancerProgress.Net: An Interactive History of
`Cancer Research Advances
`
`(cid:127) CancerProgress.Net was launched in 2011 to mark the
`40th anniversary of the US National Cancer Act,
`which led to major new investments in cancer
`research and significant increases in cancer survival.
`The site is intended to provide a dynamic and
`interactive history of progress against cancer, expert
`perspectives on remaining challenges, and other
`useful tools.
`
`(cid:127) The central feature of the site—the interactive
`timeline—was developed under the guidance of an
`editorial board of 17 of the nation’s leading
`oncologists and will be updated over time with
`additional cancer types, significant new advances, and
`helpful videos, links, and images.
`
`134
`
`JOURNAL OF CLINICAL ONCOLOGY
`© 2012 by American Society of Clinical Oncology
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`Clinical Cancer Advances 2012
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`cancer returns within 10 years of receiving high-dose chemotherapy
`and stem-cell transplantation, because chemotherapy typically fails to
`eradicate all myeloma cells. Several treatments for controlling growth
`of residual myeloma cells after transplantation (maintenance of re-
`mission) have been explored, but their use has thus far been hindered
`by inconsistent effectiveness and harmful adverse effects.
`However, results of two placebo-controlled phase III trials re-
`ported this year indicate that lenalidomide may be able to delay
`relapses in patients with multiple myeloma after stem-cell transplan-
`tation. In the first study, 615 patients age younger than 65 years were
`randomly assigned to maintenance treatment with either lenalido-
`mide or placebo until relapse.2 On average, the disease returned after
`41 months with lenalidomide therapy versus 23 months with placebo.
`After 4 years of follow-up, more than 70% of patients were alive in
`both groups. In the second study, 460 patients with multiple myeloma
`age younger than 71 years were randomly assigned to receive lenda-
`lidomide or placebo.3 The median time to disease progression was 46
`months in the lenalidomide group and 27 months in the placebo
`group. Lenalidomide also increased overall survival; a total of 35
`deaths occurred in the lenalidomide group compared with 53 deaths
`in the placebo group. In both studies, the benefit of lenalidomide was
`seen among all patient subgroups and was independent of patient age,
`prior use of lenalidomide, and disease stage. However, lenalidomide
`was also associated with more adverse effects and higher incidence of
`second cancers compared with placebo (7% to 8% v 3% to 4%). These
`results provide compelling evidence of improved progression-free
`survival with lendalidomide maintenance therapy. But given the un-
`certainty of the overall survival benefit and considerable risks associ-
`ated with the treatment, including myelodysplastic syndrome and
`AML, the risks and benefits should be carefully assessed to maximize
`both survival and patients’ quality of life. The association of lenalido-
`mide with second malignancies in patients with myeloma continues to
`be evaluated.
`
`Notable Advances
`Gemtuzumab ozogamicin added to standard chemotherapy im-
`proves survival of older patients with AML. Gemtuzumab ozogamicin
`was widely used to treat AML from 2000 until 2010, when it was
`withdrawn from the market based on concerns that it does not provide
`enough benefit compared with standard therapy to justify its associ-
`ated serious risks, including death. Gemtuzumab ozogamicin consists
`of an antitumor antibiotic calicheamicin that is chemically linked to an
`antibody that targets CD33, a protein found on the surface of most
`immature AML WBCs (blasts) and myeloid precursor cells.
`This year, investigators reported data from a phase III trial that
`sought to determine if the addition of gemtuzumab ozogamicin to
`standard induction (initial) and consolidation chemotherapy could
`improve outcomes of older patients with AML.4 Consolidation ther-
`apy is used to kill any cancer cells left in the body after initial therapy.
`In the study, 280 patients between ages 50 and 70 years with
`newly diagnosed with AML were randomly assigned to treatment with
`chemotherapy alone or chemotherapy plus gemtuzumab ozogamicin.
`Gemtuzumab ozogamicin was administered on a novel dosing sched-
`ule during induction; fewer doses were administered during consoli-
`dation. At 2 years, the proportion of patients who remained free of
`disease was twice as high in the gemtuzumab ozogamicin group
`of patients, an estimated 40.8% versus 17.1%. Overall and
`recurrence-free survival rates were also significantly improved in
`
`the gemtuzumab ozogamicin group (53.2% v 41.9% and 50.3% v
`22.7%). However, this benefit was not observed in patients with
`high-risk subtypes of the disease.
`Although the addition of gemtuzumab ozogamicin increased the
`hematologic toxicity associated with chemotherapy, unlike previous
`studies, this trial found there was no increase in induction mortality or
`death in remission. This study, along with three other European trials
`reported at the 53rd Annual Meeting of the American Society of
`Hematology in December 2011, shows the addition of gemtuzumab
`ozogamicin to chemotherapy seems to improve outcomes and even
`prolong the survival of older patients with AML. Gemtuzumab ozo-
`gamicin is currently only available as an investigational agent. Pfizer is
`considering its next steps with this important antibody-drug conju-
`gate for older adults with AML.
`New chemotherapy-antibody combination delays disease progres-
`sion in lymphoma. Mantle-cell lymphoma is a rare but difficult-to-
`treat form of lymphoma. Even with treatment, patients live a median
`time of just 3 to 6 years after diagnosis. A chemotherapy drug called
`bendamustine has previously been used in combination with the
`antibody rituximab to treat relapsed and recurrent mantle-cell lym-
`phoma and indolent (slow growing) lymphoma, but the efficacy of
`this combination in previously untreated patients has been unclear.
`Long-term results of a phase III trial that explored the efficacy of
`bendamustine plus rituximab (B-R) versus CHOP (cyclophospha-
`mide, doxorubicin, vincristine, and prednisone) chemotherapy plus
`rituximab (CHOP-R) in 514 patients with indolent and mantle-cell
`lymphomas were reported this year.5 The median patient age was 64
`years. Investigators found that B-R extended the median time to
`disease progression by more than 3 years (69.5 months with B-R v 31.2
`months with CHOP-R) and was better tolerated than CHOP-R. Over-
`all survival did not differ between the two treatment groups, partly
`because nearly half of the CHOP-R patients whose disease continued
`to progress were permitted to receive B-R, and partly because survival
`for indolent lymphomas tends to be long (10 to 15 years).
`This study demonstrates that B-R is superior to the standard
`treatment (ie, CHOP-R) for patients with previously untreated indo-
`lent lymphoma and elderly patients with mantle-cell lymphoma.
`Once the final report of this trial is published, the results are expected
`to change clinical practice, especially in the United States, where the
`CHOP-R regimen has been widely used.
`Intro-
`Ponatinib is active in treatment-resistant CML and ALL.
`duction of BCR/ABL TKI drugs revolutionized the treatment of pa-
`tients with CML and Philadelphia chromosome (Ph) –positive ALL.
`However, patients harboring a specific alteration in the BCR/ABL
`protein T315I are resistant to the TKI drugs. But results from an
`ongoing phase II study showed that a new, rationally designed TKI
`drug, ponatinib, is active in this group of patients.6
`In the study, nearly all of the 449 patients enrolled had experi-
`enced failure of two or more previous treatments with BCR/ABL TKIs.
`Remissions occurred in 65% of patients with chronic-phase CML with
`the T315I alteration, and hematologic responses (recovery of healthy
`blood cell counts) were observed in 37% of patients with Ph-positive
`ALL with T315I. These results suggest that ponatinib is an active agent
`for these two populations of patients.
`Small trial reveals a potential new initial treatment for elderly
`patients with CLL. The standard therapy for CLL, fludarabine, is
`effective in elderly patients, but it carries significant risk of adverse
`effects, including treatment-related death. Therefore, older patients
`
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`
`© 2012 by American Society of Clinical Oncology
`Downloaded from jco.ascopubs.org on July 21, 2014. For personal use only. No other uses without permission.
`Copyright © 2013 American Society of Clinical Oncology. All rights reserved.
`
`135
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`IMMUNOGEN 2018, pg. 5
`Phigenix v. Immunogen
`IPR2014-00676
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`Roth et al
`
`with CLL are in great need of new effective but less toxic treatments.
`Interim results of a phase Ib/II study suggest that a new drug candidate
`may fulfill this unmet clinical need.7
`In the study, 31 patients were treated with the investigational
`drug ibrutinib, which targets Bruton’s tyrosine kinase and thereby
`blocks cancer cell division and spreading. The study assessed two
`different doses of ibrutinib both in relapsed and treatment-resistant
`patients with CLL as well as in patients who had no prior treatment.
`The median patient age was 71 years, and three quarters of patients
`were older than age 70 years. At the lower dose, patients were observed
`for a median time of 10.7 months, and during that time, 19 (73%)
`of 26 patients experienced tumor shrinkage, and 8% of those had
`complete remissions. The higher dose was not more active com-
`pared with the lower dose. These findings indicate that ibrutinib
`should be explored further as the first treatment for elderly patients
`wi