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LUNG CANCER New Therapies for Histologies Other than Adenocarcinoma CHAIR David E. Gerber, MD The University of Texas Southwestern Medical Center Dallas, TX SPEAKERS Paul K. Paik, MD Memorial Sloan Kettering Cancer Center New York, NY Afshin Dowlati, MD Case Western Reserve University Cleveland, OH
SQUAMOUS, SMALL CELL, AND RARE LUNG CANCERS Beyond Adenocarcinoma: Current Treatments and Future Directions for Squamous, Small Cell, and Rare Lung Cancer Histologies David E. Gerber, MD, Paul K. Paik, MD, and Afshin Dowlati, MD OVERVIEW Lung cancer encompasses a diverse spectrum of histologic subtypes. Until recently, the majority of therapeutic advances were limited to the minority of patients with adenocarcinoma. With the advent of comprehensive genomic profiling of squamous and small cell lung cancers, new therapeutic targets have emerged. For squamous tumors, the most promising of these include fibroblast growth factor receptor (FGFR), the phosphatidylinositol 3-kinase (PI3K) pathway, discoidin domain receptor 2 (DDR2), and G1/S checkpoint regulators. In 2014, the antiangiogenic agent ramucirumab was approved for all non–small cell lung cancer (NSCLC) histologies, including squamous tumors. Immunotherapeutic approaches also appear to be promising for these cases. Genomic analysis of small cell lung cancer has revealed a high mutation burden, but relatively few druggable driver oncogenic alterations. Current treatment strategies under investigation are focusing on targeting mitotic, cell cycle, and DNA repair regulation, as well as immunotherapy. Pulmonary neuroendocrine tumors represent a diverse spectrum of diseases that may be treated with somatostatin analogs, cytotoxic agents, and molecularly targeted therapies. Radiolabeled somatostatin analogs and combinations with mammalian target of rapamycin (mTOR) inhibitors also show potential. Large cell neuroendocrine tumors share numerous clinical, pathologic, and molecular features with small cell lung cancer; however, whether they should be treated similarly or according to a NSCLC paradigm remains a matter of debate. Recent therapeutic advances in lung cancer have been almost exclusively limited to adenocarcinoma histology. Molecular profıling efforts to identify genomic alterations, driver oncogenes, and druggable targets have focused on adenocarcinoma. Until recently, antiangiogenic treatments were limited to nonsquamous NSCLC because of concerns of heightened toxicity (life-threatening hemoptysis) in squamous cases. Additionally, use of the well-tolerated, convenient, and effective cytotoxic agent pemetrexed is also restricted to nonsquamous cases because of inferior outcomes in squamous cases. Lung cancer encompasses numerous diverse histologic types (Sidebar 1). After decades of inactivity, recent years have seen advances in our understanding and treatment of lung cancer types beyond adenocarcinoma. Genomic alterations that may provide therapeutic targets have been identifıed in squamous cell carcinoma, and newer antiangiogenic agents appear to be tolerated in this histologic subtype. Gene sequencing efforts in small cell lung cancer have identifıed one of the highest mutational burdens of any malignancy, and prophylactic cranial irradiation in extensive stage disease has been shown to improve neurologic outcomes and overall survival. Although advances for less common lung tumors, such as large cell carcinoma and bronchial carcinoids, have been hampered by their low frequency and a lack of consensus on disease categorization, recent data suggest that certain molecularly targeted agents, liver-directed therapies, and radiolabeled somatostatin analogs may improve outcomes. This review provides an overview of the current approach and future directions for these diverse malignancies. SQUAMOUS CELL CARCINOMA Recently, genotyping efforts—ranging from the comprehensive, such as The Cancer Genome Atlas’ squamous lung cancer study, to the individual, such as the characterization of FGFR1 amplifıcation and DDR2 mutations—have brought to light a number of putative therapeutic targets that appear to occur in toto in more than half of all patients’ tumors. What follows is a summary of recent diagnostic and therapeutic developments aimed at improving the outcomes of patients with this disease. Squamous tumors account for 20% to 30% of all NSCLC cases. 1 The prototypical squamous cancer is characterized by From The University of Texas Southwestern Medical Center, Dallas, TX; Memorial Sloan Kettering Cancer Center, New York, NY; Case Western Reserve University, Cleveland, OH. Disclosures of potential conflicts of interest are found at the end of this article. Corresponding author: David E. Gerber, MD, Division of Hematology-Oncology, Harold C. Simmons Cancer Center, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Mail Code 8852, Dallas, TX 75390; email: david.gerber@utsouthwestern.edu. © 2015 by American Society of Clinical Oncology. asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK 147
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AMERICAN SOCIETY OF CLINICAL ONCOLO
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American Society of Clinical Oncolo
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Controversies in Neoadjuvant Therap
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Managing Ovarian Cancer in the Olde
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Updates in the Multimodality Manage
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PEDIATRIC ONCOLOGY Real-Time Molecu
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2015 ASCO Annual Meeting Disclosure
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2015 Educational Book Expert Panel
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James Marshall, PhD Roswell Park Ca
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2015 Annual Meeting Supporters* MIS
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David Yurman Corporate Allies Conqu
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INVITED ARTICLES This year’s invi
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MICHAEL A. POSTOW Managing Immune C
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PRECISION THERAPY FOR RECTAL CANCER
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GERM CELL TUMORS: LOOKING TO THE FU
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SALVAGE CHEMOTHERAPY Salvage Therap
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NOVEL IMMUNOTHERAPY AGENTS IN METAS
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PROMISING STRATEGIES IN BLADDER CAN
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GYNECOLOGIC CANCER Cervical Cancer
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GYNECOLOGIC CANCER Managing Ovarian
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DUSKA, TEW, AND MOORE KEY POINTS A
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GYNECOLOGIC CANCER Treatment of the
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CHEMOTHERAPY FOR PATIENTS WITH BMOC
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PROGRESS IN HEAD AND NECK SQUAMOUS
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ISAACSSON VELHO, CASTRO JR, AND CHU
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HEALTH SERVICES RESEARCH AND QUALIT
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INDUSTRY AND ONCOLOGY KEY POINTS F
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INDUSTRY AND ONCOLOGY has been “l
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INDUSTRY AND ONCOLOGY by (covered)
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CANCER CARE QUALITY: CURRENT STATE
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MANAGING OLDER PATIENTS WITH ALL Th
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MANAGING OLDER PATIENTS WITH ALL TA
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MANAGING OLDER PATIENTS WITH ALL FI
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MANAGING OLDER PATIENTS WITH ALL ra
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TREATMENT OF PHILADELPHIA CHROMOSOM
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CD19 CAR THERAPY FOR ALL FIGURE 1.
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CD19 CAR THERAPY FOR ALL 5. Zhou G,
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NEW TARGETED THERAPIES FOR iNHL New
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NEW TARGETED THERAPIES FOR iNHL TAB
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HEMATOPOIETIC CELL TRANSPLANTATION
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DAVID W. SCOTT Cell-of-Origin in Di
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DAVID W. SCOTT FIGURE 3. The Lymph2
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LYMPHOMA AND PLASMA CELL DISORDERS
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MANAGEMENT OF CLL Up-Front Manageme
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MANAGEMENT OF CLL than 17p-/TP53mut
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MANAGEMENT OF CLL could be associat
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MANAGEMENT OF CLL tion by nonmalign
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MANAGEMENT OF CLL lymphocytic leuke
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PROGNOSTIC FACTORS AND ADJUVANT RAD
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MERKEL CELL CARCINOMA Merkel Cell C
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MERKEL CELL CARCINOMA tions in PIK3
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MERKEL CELL CARCINOMA 32. Leonard J
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PERFUSION AND INFUSION IN THE ERA O
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NEOADJUVANT THERAPY OF MELANOMA Neo
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SULLIVAN ET AL FIGURE 1. Relevant S
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SULLIVAN ET AL Resistance to BRAF i
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SULLIVAN ET AL 17. Halait H, Demart
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SULLIVAN ET AL NRAS-mutant melanoma
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KLEPIN, RODIN, AND HURRIA Treating
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KLEPIN, RODIN, AND HURRIA plication
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PERIPHERAL NEUROTOXICITY IN CANCER
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PARTRIDGE, JACOBSEN, AND ANDERSEN C
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PARTRIDGE, JACOBSEN, AND ANDERSEN c
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PARTRIDGE, JACOBSEN, AND ANDERSEN w
Page 778 and 779:
PARTRIDGE, JACOBSEN, AND ANDERSEN v
Page 780 and 781:
LESLIE R. SCHOVER Sexual Healing in
Page 782 and 783:
LESLIE R. SCHOVER tinuous ADT in pr
Page 784 and 785:
LESLIE R. SCHOVER 12. Potosky AL, H
Page 786 and 787:
CATHERINE H. VAN POZNAK TABLE 1. Wo
Page 788 and 789:
CATHERINE H. VAN POZNAK (tamoxifen,
Page 790 and 791:
CATHERINE H. VAN POZNAK TABLE 3. FD
Page 792 and 793:
CATHERINE H. VAN POZNAK premenopaus
Page 794 and 795:
SHARI GOLDFARB KEY POINTS Brea
Page 796 and 797:
SHARI GOLDFARB and friction with va
Page 798 and 799:
SHARI GOLDFARB importance both duri
Page 800 and 801:
PATIENT AND SURVIVOR CARE Moving Su
Page 802 and 803:
MAYER ET AL TABLE 1. Quality Metric
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MAYER ET AL to enhance the quality
Page 806 and 807:
MAYER ET AL FIGURE 2. (A) Infertili
Page 808 and 809:
MAYER ET AL efıcial suggests that
Page 810 and 811:
PATIENT AND SURVIVOR CARE The Chall
Page 812 and 813:
BRUERA AND PAICE Choice of Opioid a
Page 814 and 815:
BRUERA AND PAICE toxicity and proce
Page 816 and 817:
BRUERA AND PAICE effective. Basic s
Page 818 and 819:
PEDIATRIC ONCOLOGY Real-Time Molecu
Page 820 and 821:
CARROLL, RAETZ, AND MEYER KEY POINT
Page 822 and 823:
CARROLL, RAETZ, AND MEYER most are
Page 824 and 825:
CARROLL, RAETZ, AND MEYER markers a
Page 826 and 827:
PEDIATRIC ONCOLOGY Translating Surv
Page 828 and 829:
REDUCING THE BURDEN OF LATE EFFECTS
Page 830 and 831:
Page 832 and 833:
Page 834 and 835:
Page 836 and 837:
PROFESSIONAL DEVELOPMENT The Challe
Page 838 and 839:
ADVANCES IN WEBSITE INFORMATION RES
Page 840 and 841:
Page 842 and 843:
Page 844 and 845:
Page 846 and 847:
COMMUNICATION AND TECHNOLOGY: IT’
Page 848 and 849:
Page 850 and 851:
Page 852 and 853:
PATIENT-REPORTED OUTCOMES IN ONCOLO
Page 854 and 855:
PATIENT-REPORTED OUTCOMES IN ONCOLO
Page 856 and 857:
PROFESSIONAL DEVELOPMENT Trends, An
Page 858 and 859:
CLINICAL ONCOLOGY PRACTICE 2015 FIG
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CLINICAL ONCOLOGY PRACTICE 2015 (6.
Page 862 and 863:
CLINICAL ONCOLOGY PRACTICE 2015 Pro
Page 864 and 865:
ADJUVANT/NEOADJUVANT MEDICAL THERAP
Page 866 and 867:
Page 868 and 869:
Page 870 and 871:
INDICATIONS FOR ADJUVANT RADIATION
Page 872 and 873:
Page 874 and 875:
Page 876 and 877:
Page 878 and 879:
SARCOMA Latest Advances in Systemic
Page 880 and 881:
SYSTEMIC THERAPY FOR OSTEOSARCOMA A
Page 882 and 883:
SYSTEMIC THERAPY FOR OSTEOSARCOMA A
Page 884 and 885:
RETHINKING TREATMENT FOR CHONDROSAR
Page 886 and 887:
Page 888 and 889:
Page 890 and 891:
Page 892 and 893:
BONE SARCOMAS IN ADULTS local disea
Page 894 and 895:
BONE SARCOMAS IN ADULTS structure a
Page 896 and 897:
SARCOMA Well-Differentiated and Ded
Page 898 and 899:
ABBAS MANJI ET AL ticular region. 7
Page 900 and 901:
ABBAS MANJI ET AL MYXOID (ROUND CEL
Page 902 and 903:
ABBAS MANJI ET AL versus doxorubici
Page 904 and 905:
SHLUSH AND HERSHKOVITZ Clonal Evolu
Page 906 and 907:
SHLUSH AND HERSHKOVITZ FIGURE 1. Ti
Page 908 and 909:
TUMOR BIOLOGY New Strategies to Und
Page 910 and 911:
KNAPP, DHAWAN, AND OSTRANDER in dog
Page 912 and 913:
KNAPP, DHAWAN, AND OSTRANDER TABLE
Page 914 and 915:
KNAPP, DHAWAN, AND OSTRANDER 14. Fe
Page 916 and 917:
SOURBIER, SRINIVASAN, AND LINEHAN M
Page 918 and 919:
SOURBIER, SRINIVASAN, AND LINEHAN F
Page 920 and 921:
SOURBIER, SRINIVASAN, AND LINEHAN T
Page 922:
Author Index Abbas Manji, Gulam ...
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