olume 32, Issue 15S, Part | ofIl
`
`\
`
`May 20, 2014
`
`American Society of Clinical Oncology
`
`1964-2014
`
`JOURNAL oF.
`|
`CLINICAL
`ONCOLOGY
`
`www.jco.org
`
`SOth Annual Meeting
`PROPERTY OF THE
`May 30-June 3, 2014
`SeayOF
`McCormick Place
`MEDICINE
`Chicago,IL
`Genome & Co. v. Univ. of Chicago
`PGR2019-00002
`
`UNIV. CHICAGO EX. 2043
`
`INO)
`
`

`

`50th
`
`Annual Meeting of the
`American Society of Clinical Oncology
`May 30-June 3, 2014
`
`Chicago, Illinois
`2014 Annual Meeting Proceedings Part |
`
`(a supplement to the Journalof Clinical Oncology)
`
`
`
`Copyright 2014 American Society of Clinical Oncology
`
`

`

`Editor: Michael A. Carducci, MD
`
`Managing Editor: Amy Hindman
`Editorial Coordinator: Devon Carter
`
`Production Manager: Donna Dottellis
`
`Requests for permission to reprint abstracts should be directed to Intellectual Property
`Rights Manager, American Society of Clinical Oncology, 2318 Mill Road, Suite 800,
`Alexandria, VA 22314. Tel: 571-483-1300; Fax: 571-366-9530; Email: permissions@asco.org.
`Editorial correspondence and production questions should be addressed to Managing Editor,
`Annual Meeting Proceedings, American Society of Clinical Oncology, 2318 Mill Road, Suite
`800,Alexandria, VA 22314, Email: abstracts@asco.org.
`
`Copyright © 2014 American Society of Clinical Oncology. All rights reserved. No part of
`this publication may be reproducedor transmitted in any form or by any means,electronic or
`mechanical, including photocopy, recording, or any information storage and retrieval system,
`without written permission by the Society.
`
`The American Society of Clinical Oncology assumes no responsibility for errors or
`omissions in this document. The reader is advised to check the appropriate medical literature
`and the product information currently provided by the manufacturer of each drug to be
`administered to verify the dosage, the method and duration or administration, or
`contraindications. It is the responsibility of the treating physician or other health care
`professional, relying on independent experience and knowledge of the patient, to determine
`drug, disease, and the best treatment for the patient.
`
`Abstract management and indexing provided by The Conference Exchange, Cumberland,
`RI. Composition services and print production provided by Cenveo Publisher Services,
`Richmond, VA.
`
`BeeWITH
`
`SOY INK].
`
`

`

`
`
`CONTENTS©
`
`
`
`2014 ASCO ANNUAL MEETING PROCEEDINGS
`
`Special Award Lecture ADStracts .........:-:cssscscsseesseneeeenessesnteenennenercanennnanirrecnenscsnenensaeydeseneeseeveneenes
`Plenary (Abstracts LBA1 ~ LBAG) sessssssssssssesssssesessssnsnnnnnenenennseressansssanannnenteeseresasunnnnnnnnnnnnnneenegsessiats
`Breast Cancer-HER2/ER
`Scheduled presentations (Abstracts 500 - TPS672) sesverssceeerpenseoesedenyeeseaensegeneenessenessseanseneaeessegeneeerseeeneeestevnees
`Breast Cancer-Triple-Negative/Cytotoxics/Local Therapy
`Scheduled presentations (Abstracts 1000% - TPSN49) ccecccscssssssscctssrseneenssneeeessserenaerscerssneneeneeeseestneaenaeeegerney
`Cancer Prevention/Epidemiology
`Scheduled presentations (Abstracts 1500 - TPS1618) .-sesssscscsessessecerntsrsenrsesssnerenssneenennennssstessssentavensetanenscteseaans
`Central Nervous System Tumors
`Scheduled presentations (Abstracts 2000 - TPS2112Z) ..s-scsereereeserresseneenecseesteseraserensersssortcessneensnnancenseanasenesgnes
`Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
`Scheduled presentations (Abstracts 2500 - TPS2647) .......seeeeesaees davesesaaessueneeaseneeeeeaenenserensesecenenauneaedesneneeeaneae
`Developmental Therapeutics—immunotherapy
`Scheduled presentations (Abstracts 3000 ~ TPS3134) severeseesssoseeeeve Sosceetnasoceneecsseveesscssesaeetseeensesneetensaess
`Gastrointestinal (Colorectal) Cancer
`Scheduled presentations (Abstracts 3500 - TPS3667) vrsccorrcsereesevesesscoveeatenvnnseeser sevesseneaee Seeteeessseseesenenersessuars
`Gastrointestinal (Noncolorectal) Cancer
`Scheduled presentations (Abstracts 4000 - TPSA163) «-rrereossssesereeseeseentseessrentestsesenentssrenneneatnanenesnnensteseenuene
`Genitourinary (Nonprostate) Cancer
`Scheduled presentations (Abstracts 4500 - TPS4607) ...cccscssssscsssrccnrsacasesesecessesssseenecnacscesencesesecusevsesseserseseecase
`
`1s
`3s
`
`5s
`
`48s
`
`84s
`
`14s
`
`142s
`
`179s
`
`213s
`
`255s
`
`296s
`
`
`
`continued on following page
`
`
`:
`
`Journal ofClinical Oncology (ISSN 0732-183N) is published 36 times a year, three times monthly, by the American Society of Clinical Oncology, 2318 Mill Road, Suite 800,
`Mexandria, VA 22314. Periodicals postage is paid at Alexandria, VA, andat additional mailing offices. Publication Mail Agreement Number 863289.
`Fditorial correspondence should be addressed to Stephen A. Cannistra, MD, Journal of Clinical Oncology, 2318 Mill Road, Suite 800, Alexandria, VA 22314. Phone:
`703-797-1900; Fax: 703-684-8720, E-maih joo@asco.org, Internet: www. jco.org.
`Journal of Clinical Oncology®is a registered trademark of American Society of Clinical Oncology, Inc.
`POSTMASTER: ASCO members should send changes of address to American Society of Clinical Oncology, 2318 Mill Road, Suite 800, Alexandria, VA 22314,
`Noumenbers should send changes of address to Journal ofClinical Qucelogy CustomerService, 2318 Mill Road, Suite $00, Mexandria, VA 22314,
`
`
`effective September1, 2013; United States and possessions: individual, $607 one year, $1,153 two years: singleissue, $40, International: individual,
`2014 annual subscription rate
`SH12 oneyear, $1,600 twoyears; single issue,
`$50, Institutions: bundled(print + online): Vier 1: $944 US, $1,310 InvTier 2: $1,089 US, $1,444lack, Ticr 3: $1,572 US, $1,914
`Inv’ Vier 4: contact JO for quote, Institutions: online only, worldwide: Vier 1: $807; Tier 2: $924; Tier 3: $1,334; Tier +: contact JCO for quote. See ww w,jco.org/ratecard for
`descriptions ofeachtier, Student and resident: United States and possessions: $289; all other countries, $401. ‘To receive student/residentrate, orders must be accompanied by name
`of affiliated insuiation, date of term, andthesignature ofprogranvresidency coordinator oninstitution Jetterhead. Orders will bebilled at individual rate until proof of status 1s
`received. Current prices areint cffect for back volumes andhack issues. Back issues soldin conjanction with a subscriptionrateare on a proratedbasis. Subscriptions are accepted ona
`’
`.
`:
`:
`.
`*
`.
`.
`ar
`a
`+
`:
`aby Meee
`FC
`emaICy
`f2ananth basis, Prices are subject to change without notice, Singleissues, bophaerataiUMakeevsedited quantities andare offeredforsale subject to availability.CO Legacy
`Atchive(electronic back issues from January 1983 through December 1998)ds.alpaaxpikplenplgasginquire.
`
`

`

`
`
`ccscssscessseeesecceestensssessasenseespeneensrsravarsuensneeveapaneneaag eas
`
`Genitourinary (Prostate) Cancer
`
`Scheduled presentations (Abstracts 5000 - TPSSIUNN) cccccccsssesccreseeesecerssersesneeesaetsaneertesasennaseepansenssetennrscetevenena
`Gynecologic Cancer
`Scheduled presentations (Abstracts LBAS500 = TPS5G632)
`Head and Neck Cancer
`Scheduled presentations (Abstracts 6000 - TPS6106) «0... sees eeteeenseorsertenacaarere Jeeeenenteeenneateanoneeaeereteton veveeees we
`Health Services Research
`Scheduled presentations (Abstracts 6500 - TPS6639) occ ceeecrreees debeneeecedsenenscenaasesrectenserecnuasosete deveseveveseeces
`Leukemia, Myelodysplasia, and Transplantation
`densussuegaseeeyseeteeeteneceess beeeees
`Scheduled presentations (Abstracts 7002 - TPS7128) ose eeedecsersenees
`Lung Cancer-Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers
`Scheduled presentations (Abstracts 7500 - TPSTE1Z) eecccsecessceessereeseereetseretenresueeeuestesnevenuanensnuerreceaseeeestreteenre
`Lung Cancer—Non-Small Cell Metastatic
`Scheduled presentations (AbstractS 8000 ~ 8135) w--seereetenenceens veeveeeeess veeeenees cennteneesenesseees peeeeeees deensecneeees
`Lymphomaand PlasmaCell Disorders
`Scheduled presentations (Abstracts 8500 - TPS8630) ......
`Melanoma/Skin Cancers
`Scheduled presentations (Abstracts LBAQOO0% - TPS9121) «0... etn veveseseuee Veesduesceveeeuenseuceeeaeseaeeeeees heeeees
`Patient and Survivor Care
`Scheduled presentations (Abstracts LBA9500% - TPS9664) seein Ceneenneeeeneeseseeeeeeetes deveeeeeeeeeseees
`Pediatric Oncology
`Scheduled presentations (Abstracts 10000 ~ TPS10095)....... eee secueseccenaneesseeseunuecersesesasourssnegestas
`Sarcoma
`Scheduled presentations (Abstracts 10500 - TPS10604) ......... ves cesene vnu tune eeauugvvereiabbeanuasnreevree Syedepeaeteesnateese
`
`
`
`
`
`Tumor Biology
`Scheduled presentations (Abstracts 11000 - TPSIN36) 0... cece cee eteen enter eceenie tent neces tite neereeneesates
`
`Author Index oo...ccc ce recevereeseesservevssanesnesesreeesesuestnmuesivereneseenteee deeveaeeeenaenveres
`
`323s
`
`351s
`
`384s
`
`410s
`
`445s
`
`477s
`
`506s
`
`539s
`
`571s
`
`602s
`
`644s
`
`668s
`
`695s
`
`730s
`
`

`

`Gynecologic Cancer
`
`5508
`
`Oral Abstract Session, Sat, 1:15 PM-4:15 PM
`
`Comparison of treatment invasiveness between upfront debulking surgery
`versus interval debulking surgery following neoadjuvant chemotherapyfor
`stage HI/IV ovarian, tubal, and peritoneal cancers in phaseIII randomized
`trial: JCOGO602., Presenting Author: Takashi Onda, Departmentof Gynecol-
`ogy, Kitasato University School of Medicine, Sagamihara, Japan
`Background: We conducted a phaseIII trial comparing upfront primary debulking
`surgery (PDS) and NAC for stage III/IV ovarian, tubal and peritoneal cancers
`(JCOGO602). Two preceding studies, EORTC55971 and CHORUS, successfully
`demonstrated non-inferior survival of patients treated with NAC. However,
`invasiveness of treatment (Tx) has not yet fully been analyzed. to prove efficacy
`of NAC compared to standard Tx,
`it
`is necessary to
`demonstrate apparently
`reduced invasiveness of Tx.
`(UMIN-CTR: UMINQQ0000523). Methods:
`JCOGO602 is now on-going and the primary analysis of OS is planned in 2016.
`Patients were randomized to standard arm (PDS followed by 8 cycles of
`paclitaxel and carboplatin,
`i.e. TC regimen) and NAC arm (4 cycles of TC,
`interval debulking surgery [IDS], 4 cycles of TC).
`In standard arm,
`IDS was
`optional for patients who underwent suboptimal or incomplete PDS. Surgical
`invasiveness and incidence of adverse events related to Tx were compared
`between two arms. Results: From Nov 2006 to Oct 2011, 301 patients (149
`standard arm and 152 NAC arm) were randomized. !n standard arm 147/149
`underwent PDS and 46 of them and 132/152 in NAC arm underwent IDS.
`Though pelvic and paraaortic lymphadenectomy (PLA/PALA) were morefre-
`quently performedin NAC arm (P<0.01), frequency of bowel or organ resection
`was lower in NAC arm (P<0.01). In a comparison between PDS in standard arm
`and IDS in NAC arm, blood/ascites loss (<0.01), albumin transfusion (<0.01),
`and G3/4 adverse events after surgery in total were fewerin IDS. Conclusions: Tx
`with NAC is less invasive than standard Tx. When non-inferior survival will be
`confirmed in this trial and new staging system is established, Tx with NAC can
`become a new standard Tx for advanced ovarian cancer. Clinical trial informa-
`tion: UMINOQOQ000523.
`
`PLA
`PALA
`Bowelor organ resection
`Treatment-related death
`Comparison of surgery
`Blood/ascites loss (median)
`Red cell transfusion
`Alb transfusion
`G3/4 adverse events
`During surgery
`After surgery
`
`Standard arm
`(N=149)
`57
`27
`66
`2
`PDS (N=147)
`3,235 ml
`75
`86
`
`1
`22
`
`NAC arm
`(N= 152)
`94
`65
`39
`1
`IDS (N=132)
`795 ml
`72
`35
`
`16
`6
`
`p value
`<0.01
`<0,01
`<0.01
`0.62
`
`<0.01
`0.63
`<0.01
`
`1,00
`<0.01
`
`353s
`Clinical Science Symposium, Sun, 8:00 AM-9:30 AM
`5509
`Bevacizumab and improvement of Progression-free survival
`(PFS)
`for
`patients with the mesenchymal molecular subtype of ovarian cancer,
`Presenting Author: Boris J. N. Winterhoff, Division of Gynecologic Surgery,
`Departmentof Obstetrics and Gynecology, MayoClinic Rochester, Roches-
`ter, MN
`Background:
`ICON7 demonstrated that the addition of bevacizumab to
`carboplatin and paclitaxel improvesprogression free survival (PFS), but not
`overall survival (OS)in first-line treatment of ovarian cancer. Our aim wasto
`determineif response to bevacizumab was associated with the molecular
`Classification as described by The Cancer GenomeAtlas (TCGA) project.
`Methods: Core biopsies from formalin fixed paraffin embedded (FFPE)
`tissue blocks were examined to ensure >70% tumor nuclei from 425 of
`455 ICON7 patients enrolled in Germany. Quality Illumina Whole-Genome
`DASLHT global gene expression data was generatedto stratify 380 (89%)
`patients into four TCGA subclassifications. Median PFS with 95% confi-
`denceintervals (Cl) and log rank tests were used to evaluate treatment
`effect on PFS in the presence of non-proportional hazards. Results:
`Molecularclassification was as follows: 86 were differentiated (23%), 124
`immunoreactive (33%), 73 mesenchymal (19%), and 97 proliferative
`(25%). The groups were balanced overtreatment arms. 267 (70.3%) were
`of serous histology. Patients with serous Carcinomas of mesenchymal
`subtype obtained the greatest benefit from bevacizumab with an improve-
`ment of median PFS of 9.5 months (25.5 [95%Cl 21.1, NAl vs. 16 [95%Ci
`10.5, NA] months, p=0.053). In contrast, the differentiated, immunoreac-
`tive and proliferative subtypes demonstrated median PFS improvementsof
`5.8 (19.4 (18.6, NAl vs. 13.6 [9.7, 32.7], p=0.35), 3.4 (17.9[15.9, NA]
`vs. 14,6 [12.4, NA], p=0.38) and 3.2 months (21.5 [19.8, 29} vs. 18.3
`(13.8, NA], p=0.76), respectively. Patients with mesenchymal tumors or
`high risk clinical characteristics (suboptimal stageIII, all stage 1V) (46% of
`cohort) demonstrated a 7.3 month improvement
`in median PFS with
`bevacizumab (19.8 (18.3, 23.7] vs. 12.5 (10.1, 16.2] months, p<0.01).
`Conclusions: Assignment to molecular subclassifications based on gene
`expression signatures was feasible using FFPE tissue, Patients with
`mesenchymal subtype ovarian cancer may be most
`likely to obtain
`sustained benefit from treatment with bevacizumab.
`
`Clinical Science Symposium, Sun, 8:00 AM-9:30 AM
`5510
`Clinical Science Symposium, Sun, 8:00 AM-9:30 AM
`5511
`Prospective evaluation of
`the molecular effects of metformin on the
`Efficacy and safety of anti-PD-1 antibody (Nivolumab: BMS-936558,
`endometrium in women with newly diagnosed endometrial cancer: A
`ONO-4538)in patients with platinum-resistant ovarian cancer, Presenting
`window of opportunity study. Presenting Author: Pamela T. Soliman, The
`Author: Junzo Hamanishi, Kyoto University, Kyoto, Japan
`University of Texas MD Anderson Cancer Center, Houston, TX
`Background: Programmed death-1 (PD-1) is a co-inhibitory receptor ex-
`Background: Metformin reduces cancer incidence and improves overall
`pressed on activated T Cells which regulates antitumor immunity. Niv-
`olumabis a fully-humanized IgG4 that blocks the engagement of PD-1 by
`survival in diabetic patients. Preclinical studies have shown that metformin
`PD-1 ligands. Here we report
`the first
`trial
`for clinical application of
`decreases endometrial cancer (EC) cel! growth by activation of AMPK and
`nivolumab in ovarian cancer patients. Methods: Nivolumab was adminis-
`mTOR inhibition. The purposeof this study was to determine the effects of
`tered every 2 weeks to patients with advanced or relapsed, platinum—
`short-term metformin on serum and tumor biomarkers in women diagnosed
`resistant ovarian cancer, at the doses of 1 or 3 mg/kg during two cohort
`with EC. Methods:
`In this IRB approved, prospective trial, women with
`examination (10 patients each). The phase I! efficacy trial defined 1°
`newly diagnosed EC underwent a pre-treatment blood draw/endometrial
`endpoint of response rate, and second endpoints of safety, and disease
`biopsy, were administered oral metformin 850 mg daily for a minimum of
`control rate. Patients receivednivolumab up to 6 cycles (4 doses/cycle) of
`treatmentor until PD or disease progression. Response rate was assessed
`seven days, and then underwent post-treatment blood draw/definitive
`by RECIST v1.1, and adverse events were evaluated by CTCAE v4.0. The
`surgery. Pre- and post- serum analyses were performed. Immunohistochemi-
`data werecut-off on January 1, 2014. Results: Fifteen patients were treated
`cal analyses on tumortissue from the pre- and post-treatment samples were
`with nivolumab (1 mg/kg: n=10, 3mg/kg: n=5), and evaluated. Median
`compared to evaluate molecular changes in the PISK/AKT pathway,
`duration of therapy was 14 wks, There was one patient who had severe
`apoptosis, proliferation, and AMPK activity. Results: Twenty patients
`adverse drug reaction with fever, disorientation and gait disturbance.
`completed the study. Median age and BMI were 54 years (range 27-68)
`Clinical response rates were shownin Table. At the time of data cut off, one
`and 36.0 kg/m? (range 21.9-50.0), respectively. Median waist circumfer-
`of the three partial responders had responsesfor 5 months, and the other
`ence was 113 cm (range 80-156). Median duration of metformin treatment
`two were on study with response for 4 and 10 months. Conclusions:
`Nivolumabat 1 mg/kg cohort is well tolerated and has encouragingclinical
`was 10 days (range 7-24). A majority of women had endometrioid
`efficacy for advanced or
`relapsed, platinum-resistant ovarian cancer
`adenocarcinomas (86.7%) and were early stage (93%). Two patients were
`patients. 3 mg/kg cohort is now under investigation. Clinical trial informa-
`noted to have KRAS mutations. After treatment with metformin, there were
`tion: UMINQ00005714.eoSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSS
`significant decreases in serum IGF-1 (p=0.046), omentin (p=0.007),
`Tota!
`insulin (p=0.012), C-peptide (p=0.018), and leptin (p=0.0035). Compari-
`Dose DCREaRRC(n) CR PR sD PD NE RR
`
`
`
`
`
`
`
`
`son of pre- and post-treatment tissue samples showed decreasedlevels of
`(mer
`(20%)
`(50%)
`phospho-AKT (90%, p=0.0002), phosphor-S6rp (70%, p=0.057), and
`10
`1 (mg/kg)
`0
`2
`3
`4
`1
`2/10
`5/10
`phosphor-p44/42MAPK (83.3%, p=0.0038). There was no difference in
`ms
`(33%)
`(67%)
`3 (mg/kg)
`1/3
`2/3
`Ki67, phosphor-ACC, or caspase 3 staining in pre- and post-treatment
`samples. These changes did not correlate with BMI. Conclusions: tn this
`1
`5
`4
`3
`0
`13
`Total
`3/13
`7/3
`
`prospective phase O study we demonstrate that
`relevant serum and
`(23%)
`(54%)
`molecular changes occur in patients with newly diagnosed ECafter a short
`response rate; CR+PR; DCR: disease contro!
`rate;
`course of low dose metformin. Decreased circulating insulin and down
`regulation of the PISK/AKT pathway signaling at the tissue level
`likely
`results in mTOR inhibition and a decrease in cell growth. Clinical
`trial
`information: NCI-2012-01796.
`
`0
`
`1
`
`1
`
`1
`
`0
`
`3
`
`Abbreviations: RR:
`CR+PR+SD.
`
`
`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`
`
`
`