Year in Review

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  • Year in Review |

    In 2018, several trials in breast cancer have shown efficacy of strategies that rely on novel markers, including gene expression assays or pathological complete response. The relevance of targeted strategies in patient subgroups and of immunotherapy efficacy were demonstrated.

    • Nadia Harbeck
    •  & Rachel Wuerstlein
  • Year in Review |

    In 2018, the acute myeloid leukaemia treatment landscape expanded notably, with several trials leading to the approval of novel targeted therapies. Furthermore, comprehensive sequencing revealed the effects of co-occurring mutations and gene expression patterns on drug sensitivity, providing hope that future treatments will be increasingly precise and personalized.

    • Courtney D. DiNardo
    •  & Alexander E. Perl
  • Year in Review |

    Perioperative chemotherapy is the standard of care for localized gastric cancer (GC). In 2018, additional postoperative radiotherapy was found to be ineffective; although, docetaxel was found to be superior to epirubicin in perioperative three-drug chemotherapy regimens. Validated biomarkers are needed for benefit from immunotherapy in advanced-stage GC. Metachronous GC can be prevented by Helicobacter pylori eradication.

    • Florian Lordick
    •  & Elizabeth C. Smyth
  • Year in Review |

    Breakthrough findings reported in 2018 provide the foundations for paradigm shifts in the care of patients with ovarian cancer. These results have implications for treatment in the first-line setting (with improved and refined use of established treatment modalities), firmly introduce concepts of consolidation and maintenance therapy, and enable more accurate prediction of drug sensitivity and resistance.

    • Amit M. Oza
  • Year in Review |

    In 2018, advances in the treatment of non-small-cell lung cancer (NSCLC) have been observed both in trials of immunotherapies and targeted agents, leading to dramatically improved options for patients with metastatic and stage III NSCLC.

    • Jennifer W. Carlisle
    •  & Suresh S. Ramalingam
  • Year in Review |

    In 2018, the results of multiple phase III trials in metastatic renal cell carcinoma (mRCC) were presented. A phase III noninferiority trial demonstrated the importance of careful patient selection before cytoreductive nephrectomy. Additionally, three randomized phase III trials demonstrated the superiority of combination therapy with an immune-checkpoint inhibitor backbone versus sunitinib in patients with treatment-naive mRCC.

    • Moshe C. Ornstein
    •  & Brian I. Rini
  • Year in Review |

    In 2017, three groundbreaking immunotherapies for relapsed and/or refractory B-cell acute lymphoblastic leukaemia (ALL) were approved based on impressive outcomes observed in clinical trials. Additional breakthroughs included seminal research into ALL genomics and the importance of adherence to chemotherapy, which will have direct implications for clinical care.

    • David T. Teachey
    •  & Stephen P. Hunger
  • Year in Review |

    Data published in 2017 underscore the benefit of optimizing anti-HER2 therapy in early stage high-risk HER2-positive disease, and of capecitabine in patients with residual disease after optimal neoadjuvant therapy. In the advanced-stage setting, endocrine therapy combined with cyclin-dependent kinase 4/6 inhibitors, or olaparib could become the preferred option.

    • Jose Perez-Garcia
    •  & Javier Cortes
  • Year in Review |

    2017 saw the publication of clinical trial data and the approval of new treatment approaches for metastatic urothelial carcinoma. Pembrolizumab is now a well-established treatment for patients with disease progression after cisplatin, with high-level evidence supporting its superiority over second-line chemotherapy. For patients ineligible for cisplatin, atezolizumab and pembrolizumab provide meaningful clinical benefit as frontline therapies.

    • Joaquim Bellmunt
    •  & Rosa Nadal
  • Year in Review |

    In 2017, results from phase III trials demonstrated the impressive safety and efficacy of adjuvant targeted and immune therapies in patients with resectable stage III–IV melanoma, and raised questions about the surgical management of patients with microscopic sentinel-lymph-node metastases. For patients with unresectable disease, new overall survival data added to the debate about the relative benefits of single-agent anti-PD-1 versus combined anti-PD-1 and anti-CTLA-4 immunotherapy.

    • Michael A. Davies
    •  & Keith T. Flaherty
  • Year in Review |

    2017 has been full of new discoveries that will influence the treatment of colorectal cancer. In the adjuvant setting, 3 months of chemotherapy might now be considered a new standard of care. Various other new treatments and promising biomarkers have also become available that will improve survival outcomes and the quality of life of many patients with metastatic disease.

    • Alberto Puccini
    •  & Heinz-Josef Lenz
  • Year in Review |

    In 2017, major advances in the treatment of non-small-cell lung cancer (NSCLC) continued to emanate from the fields of molecularly targeted therapy and immunotherapy. In the former, new drugs with improved efficacy and reduced toxicity entered the clinic; in the latter, immune-checkpoint inhibition proved efficacious after chemoradiotherapy for stage III disease, but had disparate results in the frontline treatment of stage IV disease.

    • David F. Heigener
    •  & Martin Reck
  • Year in Review |

    Data obtained in the past year underscored the benefit of a triplet regimen comprising bortezomib, lenalidomide, and dexamethasone for patients with newly-diagnosed multiple myeloma, and have provided high-level evidence supporting the safety of adding daratumumab to standard-of-care doublets for those with relapsed and/or refractory disease. As a result, achieving minimal residual disease-negativity at any stage of myeloma is now a realistic possibility.

    • Prashant Kapoor
    •  & S. Vincent Rajkumar
  • Year in Review |

    In 2016, two major trials provided conflicting evidence regarding the role of 1 year of adjuvant therapy with sunitinib for patients with high-risk renal-cell carcinoma. In the second-line metastatic setting, updated data from key trials showed that cabozantinib improved overall survival over everolimus, and nivolumab was associated with a better quality of life compared with everolimus. Finally, a phase II study in previously untreated patients showed cabozantinib to be superior to sunitinib.

    • Laurence Albiges
    •  & Toni K. Choueiri
  • Year in Review |

    In 2016, the pace of biological insights into small-cell lung cancer (SCLC) was reflected in new treatment approaches that have suggested meaningful clinical benefit to patients. We focus on three highlights of 2016: preclinical studies defining NFIB as a putative driver of metastasis, and two clinical studies; one that assessed the efficacy of an agent targeting the Notch ligand DLL3, and the other that explored T-cell checkpoint-blockade therapies targeting PD-1 and CTLA-4.

    • Charles M. Rudin
    •  & John T. Poirier
  • Year in Review |

    In 2016, novel findings on the role of predisposing gene variants in sarcoma oncogenesis were published, as well as studies addressing novel molecular classifications and results from randomized controlled trials highlighting successful new treatments. Herein, we discuss these meaningful advances.

    • Jean-Yves Blay
    •  & Isabelle Ray-Coquard
  • Year in Review |

    In 2016, results of an extensive trial broadened the range of malignancies that can be treated with everolimus to include neuroendocrine tumours (NETs) of the lung and gastrointestinal tract. Furthermore, studies aimed at identifying biomarkers with increased specificity, and at better defining high-grade NETs have enabled substantial progress towards delivering effective targeted treatments to patients with NETs.

    • Massimo Falconi
    •  & Stefano Partelli
  • Year in Review |

    In the past year, clinical trials have provided important information on strategies to decrease treatment-associated toxicities in patients with head and neck cancer. In addition, the FDA approved the first immunotherapeutic agents for patients with recurrent and/or metastatic disease, based on the observation of durable responses to pembrolizumab in a phase Ib trial, and demonstration of improved survival and quality of life with the use of nivolumab versus chemotherapy in a phase III trial.

    • Alain P. Algazi
    •  & Jennifer R. Grandis
  • Year in Review |

    In 2015, academic-led trials provided evidence for safe de-escalation of adjuvant treatment in early stage breast cancer and answered important questions related to adjuvant regional irradiation and optimal first-line chemotherapy in advanced-stage disease. Furthermore, the development of novel therapies and potential tools for treatment tailoring will offer new hope to patients with breast cancer.

    • Martine J. Piccart
    •  & Isabelle Gingras
  • Year in Review |

    In 2015, advances in immunotherapy for metastatic melanoma have come to fruition, with phase III data supporting the combination of ipilimumab and nivolumab as first-line therapy. Understanding the mechanisms involved in an effective antitumour immune response are now key to further advances. Several studies published in 2015 have increased our understanding of the complex relationships that exist between our immune system and malignancy.

    • Elizabeth I. Buchbinder
    •  & F. Stephen Hodi
  • Year in Review |

    Lung-cancer treatment paradigms continue to advance as we exploit our growing understanding of the genetic basis of both tumorigenesis and therapy resistance. Moreover, ongoing developments with targeted therapies are improving patient outcomes, with two new drugs approved in 2015 for non-small-cell lung cancer and many others showing promise.

    • Egbert F. Smit
    •  & Paul Baas
  • Year in Review |

    Advances in key areas of research have enabled improved outcomes for patients diagnosed with ovarian cancer in the past three decades. In 2015, this trend was maintained with important progress in areas such as guideline compliance, design of targeted approaches and molecular profiling.

    • Robert L. Coleman
  • Year in Review |

    In 2015, published trials highlighted the remarkable efficacy of docetaxel combined with androgen-deprivation therapy in patients with newly diagnosed metastatic prostate cancer. Also in 2015, a large study revealing potential molecular targets for metastatic castration-resistant prostate cancer therapies was published, along with a study showing activity of PARP inhibition in patients harbouring mutations in genes governing DNA repair.

    • Julie N. Graff
    •  & Tomasz M. Beer
  • Year in Review |

    In a little over the past year, several clinical trials have evaluated new drugs in patients with metastatic colorectal cancer and gastric cancer. Furthermore, genomics studies that attempted to unravel the molecular characteristics of colorectal and gastric cancer were published in 2015. The results of these endeavours will influence clinical practice in 2016 and beyond.

    • Eric Van Cutsem
    •  & Michel Ducreux
  • Year in Review |

    In 2014, no major breakthroughs were made in understanding the biology of breast cancer or its management; few novel practice-changing studies were presented or published. Nevertheless, important negative results from studies that challenge some of the current concepts, particularly in drug development, underline 2014 as a year of 'failed surrogates and precocious expectations'.

    • Fatima Cardoso
    •  & Elżbieta Senkus
  • Year in Review |

    Heterogeneity within and across tumours is increasingly recognized as a critical factor that limits therapeutic progress for many cancers. Key studies reported in 2014 describe previously unappreciated patterns of geographical and temporal heterogeneity for glioblastoma (the most-common primary CNS tumour in adults), with important implications for ongoing therapeutic studies evaluating molecular targeted therapies.

    • David A. Reardon
    •  & Patrick Y. Wen
  • Year in Review |

    The results of several clinical trials in metastatic colorectal cancer presented in 2014 will influence clinical practice. These findings include definitive data from phase III trials comparing bevacizumab and cetuximab-based therapy in the first-line, studies elucidating the value of maintenance therapy after induction treatment, and data on new agents in this disease.

    • Joleen M. Hubbard
    •  & Axel Grothey
  • Year in Review |

    In 2014, developments in our understanding of escape signalling circuits implicated in resistance to targeted agents in patients with lung cancer have led to improvements in tackling such resistance. The potential role for PET in the management of erlotinib therapy, novel combination therapies and pharmacogenomic-driven individualization of platinum-based chemotherapy represent other key advances.

    • Rafael Rosell
    •  & Niki Karachaliou
  • Year in Review |

    In 2014, strides were made in the care of haematological malignancies. In particular, the heterogeneity of multiple myeloma was unravelled, and new diagnostic criteria and frontline standards of care were proposed; new therapeutic approaches have been validated and approved in chronic lymphocytic leukaemia; and in chronic myeloid leukaemia, complete cytogenetic response was confirmed as the primary therapeutic end point.

    • Jesús F. San-Miguel
    •  & Hagop M. Kantarjian
  • Year in Review |

    In 2013, studies confirmed that HPV infection of target cells predisposes to cervical (pre)cancer. In developed countries, HPV screening revealed superior protection than cytology screening. In India, visual inspection of the cervix after acetic acid application significantly reduced cervical cancer mortality after 12 years. Improved survival for women with advanced disease was observed after adjuvant bevacizumab.

    • Chris J. L. M. Meijer
    •  & Peter J. F. Snijders
  • Year in Review |

    The year 2013 has brought more options for patients with metastatic colorectal cancer (mCRC) with new ways to combine traditional agents, further refinement of predictive molecular for EGFR inhibitors and a new salvage option. Molecular profiling could identify subgroups to further improve treatment selection.

    • Hans-Joachim Schmoll
    •  & Alexander Stein
  • Year in Review |

    In 2013, the treatment of several NSCLC subtypes was refined. PROFILE-1007 and LUX-Lung 3 confirmed that targeted therapy was superior to chemotherapy, whereas NCIC BR19 and PointBreak failed to show superiority of adjuvant gefitinib and combined maintenance therapy, respectively. These studies reinforced some practices and discouraged others, underscoring the need for new prospective studies.

    • Stephen V. Liu
    •  & Giuseppe Giaccone
  • Year in Review |

    In 2013, new insights on the molecular features of cutaneous melanoma provided a paradigm shift in our understanding of the biology of this disease. Exploiting immune checkpoint blockade and the use of BRAF-targeted or MAPK-targeted agents contributed to important progress in the treatment and management of cutaneous melanoma.

    • Dirk Schadendorf
    •  & Axel Hauschild
  • Year in Review |

    2013 saw much progress in breast cancer research. Advances in high-throughput technologies continue to refine our knowledge of the molecular biology of breast cancer, and are beginning to give insight into cancer evolution, drug resistance, and how to deploy precision therapeutics.

    • Adrian V. Lee
    •  & Nancy E. Davidson
  • Year in Review |

    Next-generation sequencing analysis and characterization of the microenvironment 'field-effect' that promotes hepatocellular carcinoma (HCC) development has revealed critical players and potential targets for chemoprevention. A biomarker-based drug development strategy is needed to improve future HCC clinical trials and therapies.

    • Augusto Villanueva
    •  & Josep M. Llovet
  • Year in Review |

    Gastric cancer is a heterogeneous disease with almost one million new cases occurring annually worldwide. The year 2012 saw important successes and failures in gastric cancer treatment, and also novel insights into the molecular characterization of this disease, which may lead to the development of more-effective targeted therapies.

    • Elizabeth C. Smyth
    •  & David Cunningham
  • Year in Review |

    In 2012, we increased our knowledge of the molecular portrait of breast cancer. The BOLERO-2 and CLEOPATRA trials led to the approval of everolimus and pertuzumab; and the EMILIA trial will likely result in the approval of T-DM1. Some of these findings represent a paradigm shift in the way we think about the biology and management of breast cancer.

    • Mariana Chavez-MacGregor
    •  & Ana Maria Gonzalez-Angulo
  • Year in Review |

    In 2012, advances in molecular profiling of primary brain tumours allowed identification of subgroups of glioma and medulloblastoma that were associated with distinct prognoses and predicted treatment response. Adjuvant chemotherapy is now established for 1p/19q co-deleted anaplastic oligodendrogliomas, and may be the preferred treatment in elderly patients with glioblastoma with a methylated MGMT promoter.

    • Roger Stupp
    •  & Monika E. Hegi
  • Year in Review |

    In the past year, long-term follow-up of trials have confirmed and disproved paradigms in the treatment of colorectal cancer, and identified a chemoprevention agent. In metastatic disease, chemotherapy in unresected primary tumours was studied, and randomized phase III trials introduced new therapy options. Molecular characterization of colon and rectal tumours offers new drug targets.

    • Christina Wu
    •  & Richard M. Goldberg
  • Year in Review |

    Progress was made in major aspects of acute myeloid leukaemia in 2012. Gemtuzumab ozogamicin and decitabine were shown to improve outcomes, relapse after stem-cell transplantation might be prevented by selecting donors according to their KIR genotypes, and next-generation sequencing has provided insights into mutational patterns and disease evolution.

    • Heiko Becker
    •  & Clara D. Bloomfield
  • Year in Review |

    Melanoma has emerged as the paradigm tumor for drug development through mutation-targeted therapies (inhibitors targeting BRAF, MEK, and c-KIT) and immunotherapy. Exploring the combinations of both approaches is a challenge that will require scientific rationale and the cooperation of the pharmaceutical industry. But, with these challenges comes another opportunity to change the paradigms in drug development.

    • Alexander M. M. Eggermont
    •  & Caroline Robert
  • Year in Review |

    Options to treat late-stage castration-resistant prostate cancer continued to increase in 2011, as three agents with different mechanisms of action prolonged life and a fourth reduced the morbidity of skeletal metastases. These outcomes contrasted with the heightened controversy generated by the recommendation against PSA screening and other early detection strategies.

    • Yu Chen
    •  & Howard I. Scher
  • Year in Review |

    2011 saw improvements in our understanding of B-cell malignancies: insights into the genomic basis of chronic lymphocytic leukemia were achieved; reduced treatment intensity caused fewer toxic effects in early-stage Hodgkin lymphoma; first-line rituximab maintenance therapy improved outcome in follicular lymphoma; and selected patients with diffuse large-cell lymphoma benefited from the addition of bortezomib.

    • Paula Cramer
    •  & Michael Hallek
  • Year in Review |

    Bone-targeting treatments have transformed the quality of life of patients with metastatic bone disease. 2011 saw the emergence of denosumab—a RANK ligand-specific antibody—as a more-effective alternative treatment to bisphosphonates and of data on the use of bone-targeting treatments to prevent metastasis from breast and prostate cancers.

    • Robert E. Coleman
  • Year in Review |

    Highly clinically relevant ovarian cancer clinical research in 2011 focused on an increased understanding of the biology of the malignancy, limitations of strategies for early detection and screening, and the provocative reports of alternative primary and second-line management strategies.

    • Maurie Markman
  • Year in Review |

    Advances in non-small-cell lung cancer over the past decade have resulted in new treatments with minimal toxic effects and dramatic clinical benefits. 2010 saw continued advancement in our understanding of the molecular genetics of lung cancer and of specific targeted inhibitors with remarkable clinical benefit in selected populations.

    • Christine M. Lovly
    •  & David P. Carbone
  • Year in Review |

    Outcomes for patients with oropharyngeal cancer are determined by their tumor characteristics and associated demographics. The role of human papilloma virus-related disease for prognosis and outcomes with chemoradiotherapy is being more clearly defined. EGFR inhibitors are used in conjunction with radiotherapy, and the importance of optimizing radiation quality and minimizing toxicity is the focus of ongoing studies.

    • Bruce E. Brockstein
    •  & Everett E. Vokes
  • Year in Review |

    2010 has been another prolific year in breast cancer research with a number of original observations bringing us closer to personalized care. Studies with novel targeted agents in defined breast cancer subgroups have revealed exciting developments and highlight the importance of patient selection.

    • Michaela J. Higgins
    •  & José Baselga
  • Year in Review |

    2010 was not a year of survival breakthroughs in hematologic malignancies. However, in Hodgkin's disease and multiple myeloma new therapies emerged as the standard of care and nilotinib may be considered the treatment choice for newly diagnosed chronic myeloid leukemia.

    • Vincent T. DeVita Jr
    •  & George P. Canellos
  • Year in Review |

    Randomized phase III trials have established new standards of care for advanced biliary cancer, HER2-positive advanced gastric or gastro-esophageal junction cancer, and preliminarily, for metastatic pancreatic cancer. There is now a validated predictive biomarker to guide use of adjuvant chemotherapy in patients with stage II colon cancer.

    • Manish R. Sharma
    •  & Richard L. Schilsky