Annual Meeting Proceedings II - Newly Released Abstracts for

BREAST CANCER—HER2/ER 

LBA1 Plenary Session, Sun, 1:00 PM-4:00 PM 

Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) 

versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or 

metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a 

taxane. 

Kimberly L. Blackwell, David Miles, Luca Gianni, Ian E. Krop, Manfred Welslau, José Baselga, 

Mark D. Pegram, Do-Youn Oh, Veronique Dieras, Steven R. Olsen, Liang Fang, Michael W. Lu, 

Ellie Guardino, Sunil Verma; Duke University Medical Center, Durham, NC; Mount Vernon Cancer Centre, 

Middlesex, United Kingdom; San Raffaele Hospital, Milan, Italy; Dana-Farber Cancer Institute, Boston, 

MA; Praxis Aschaffenburg, Aschaffenburg, Germany; Massachusetts General Hospital Cancer Center and 

Harvard Medical School, Boston, MA; University of Miami Sylvester Comprehensive Cancer Center, 

Miami, FL; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; 

Department of Medical Oncology, Institut Curie, Paris, France; Genentech, South San Francisco, CA; 

Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada 

Background: T-DM1 is an antibody-drug conjugate comprising T, a stable linker, and the potent cytotoxic 

agent DM1; it incorporates the antitumor activities of T and the HER2-targeted delivery of DM1. Methods: 

EMILIA is a randomized study of T-DM1 vs XL, the only approved combination for T-refractory HER2� 

MBC. Patients (pts) received T-DM1 (3.6 mg/kg IV q3w) or X (1000 mg/m 2 PO bid, days 1–14 q3w) � 

L (1,250 mg PO daily) until progressive disease (PD) or unmanageable toxicity. Pts had confirmed HER2� 

MBC (IHC3� and/or FISH�), and prior therapy with T and a taxane. Primary end points were PFS by 

independent review, OS and safety. An interim OS analysis (efficacy boundary: HR� 0.617; p�0.0003) 

was planned at the time of the final PFS analysis. Results: 991 pts were enrolled; 978 received treatment. 

Median (med) durations of follow-up were 12.9 (T-DM1) and 12.4 (XL) months (mo). Baseline 

demographics, prior therapy and disease characteristics were balanced. There was a significant improvement 

in PFS favoring T-DM1 (med 9.6 vs 6.4 mo; HR�0.650 [95% CI, 0.549–0.771]; p �0.0001). The med 

T-DM1 OS was not reached vs 23.3 mo (HR�0.621 [95% CI, 0.475–0.813]; p�0.0005); the interim 

efficacy boundary was not crossed. T-DM1 was well tolerated with no unexpected safety signals. The most 

common grade �3 adverse events (AEs) per treatment were for T-DM1: thrombocytopenia (12.9% vs 

0.2%), increased AST (4.3% vs 0.8%), and increased ALT (2.9% vs 1.4%); for XL: diarrhea (20.7% vs 

1.6%), palmar plantar erythrodysesthesia (16.4% vs 0) and vomiting (4.5% vs 0.8%). The table lists other 

end points. Conclusions: T-DM1 conferred a significant and clinically meaningful improvement in PFS 

compared with XL. Other end points support T-DM1 as an active and well-tolerated novel therapy for 

HER2� advanced BC. 

T-DM1 XL 

OS, % (95% CI) 

1-year 84.7 (80.76–88.55) 77.0 (72.40–81.50) 

2-year 

Objective response (OR) 

65.4 (58.65–72.15) 47.5 (39.20–55.89) 

% (95% CI) 43.6 (38.6–48.6) 30.8 (26.3–35.7) 

Duration of response 

in pts with OR, 

med mo (95% CI) 

12.6 (8.38–20.76) 6.5 (5.45–7.16) 

Dose reduction, % 16.3 X 53.4 

L 27.3 

AEs > grade 3, % 40.8 57.0 

© 2012 American Society of Clinical Oncology. Reprinted with permission.

2 Plenary Session, Sun, 1:00 PM-4:00 PM 

Long-term follow-up results of EORTC 26951: A randomized phase III study on 

adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors (AOD). 

Martin J. Van Den Bent, Khê Hoang-Xuan, Alba Ariela Brandes, Johan M Kros, 

Mathilde C.M. Kouwenhoven, Martin J. B. Taphoorn, Jean-Yves Delattre, Hans J.J.B. Bernsen, 

Marc Frenay, Cees Tijssen, Wolfgang Grisold, Laszlo Sipos, Roelien H. Enting, Winand N.M. Dinjens, 

Pim French, Charles J Vecht, Anouk Allgeier, Denis A. Lacombe, Thierry Gorlia; Erasmus University 

Medical Center, Daniel den Hoed Cancer Center, Rotterdam, Netherlands; Groupe Hospitalier Pitié- 

Salpêtrière, Paris, France; Medical Oncology Department, Bellaria-Maggiore Hospital, Azienda USL of 

Bologna, Bologna, Italy; Erasmus Medical Center, Rotterdam, Netherlands; Erasmus University Medical 

Center, Rotterdam, Netherlands; Medical Center Haaglanden/VU Medical Center, The Hague/Amsterdam, 

Netherlands; Pitie-Salpetriere Hospital-Pierre et Marie Curie Paris VI University, Paris, France; Canisius 

Wilhelmina Ziekenhuis, Nijmegen, Netherlands; Anticancer Center, Centre Antoine-Lacassagne, Nice, 

France; Elisabeth Gasthuis, Tilburg, Netherlands; Kaiser Franz Josef Hospital, Vienna, Austria; Neurooncologist 

National Institute of Neurosciences, Budapest, Hungary; Universitair Medisch Centrum Groningen, 

Groningen, Netherlands; Erasmus MC, Rotterdam, Netherlands; Medical Center The Hague, The 

Hague, Netherlands; European Organisation for Research and Treatment of Cancer Headquarters, 

Brussels, Belgium 

Background: AOD are chemotherapy-sensitive tumors especially if 1p/19q co-deleted. Between 1995 and 

2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, 

CCNU and vincristine chemotherapy (PCV) in AOD. We now present long-term follow-up. Methods: 

Patients (pts) with locally diagnosed newly diagnosed AOD were randomized between radiotherapy (RT, 33 

x 1.8 Gy) and the same RT followed by 6 cycles of standard PCV (RT/PCV). Primary endpoints were 

overall survival (OS) and progression-free survival (PFS). 1p/19q status, IDH status and MGMT promoter 

methylation were determined in 300, 167, and 186 pts respectively. Results: Between 1996 and 2002, 368 

pts were included. At the time of analysis 281 pts (76.4%) had died. Median PFS after RT/PCV was 

significantly longer compared to RT alone (24.3 months versus 13.21 months, hazard ratio [HR] 0.66, [95% 

confidence interval (95% CI) 0.52, 0.83]). More RT arm patients received chemotherapy at progression 

(75% vs 53%). Median OS was also significantly prolonged in the RT/PCV arm (42.3 months vs 30.6 

months for the RT arm, HR 0.75 [95% CI 0.60, 0.95]). 1p/19q co-deleted patients (n � 76) treated with 

RT/PCV had improved OS compared to RT arm pts (median OS not reached vs 113 months; HR 0.54, p 

� 0.0487). In the 224 patients without 1p/19q co-deletion the difference in OS was non-significant (OS 

RT/PCV arm 25 months vs 22 months in the RT arm, HR 0.82, p � 0.18; test for interaction p � 0.22). 

There was a slight trend towards improved OS in MGMT methylated and IDH mutated tumors versus 

unmethylated and IDH wild type tumors (Table). Conclusions: The addition of PCV to RT increases PFS 

and OS in AOD. Pts with 1p/19q co-deletion appear to benefit most from the addition of PCV, with a trend 

for improved OS in pts with MGMT methylation and IDH mutations. 

Molecular features and the HR reduction for OS in the RT/PCV arm. 

Feature Status N HR 95% CI Status N HR 95% CI P 

1p/19q Co-deleted 76 0.54 0.29, 1.01 Intact 224 0.82 0.61, 1.10 0.22 

MGMT Methylated 132 0.67 0.44, 1.01 Unmethylated 54 0.80 0.46, 1.42 0.6 

IDH Mutated 77 0.59 0.33, 1.07 Wild type 90 0.72 0.46, 1.11 0.58 

Abbreviations: n: number of pts; p: p value interaction test. 

CENTRAL NERVOUS SYSTEM TUMORS 


LYMPHOMA AND PLASMA CELL DISORDERS 


Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as 

first-line treatment in patients with indolent and mantle cell lymphomas (MCL): 

Updated results from the StiL NHL1 study. 

Mathias J. Rummel, Norbert Niederle, Georg Maschmeyer, Andre G. Banat, Ulrich von Gruenhagen, 

Christoph Losem, Dorothea Kofahl-Krause, Gerhard Heil, Manfred Welslau, Christina Balser, 

Ulrich Kaiser, Eckhart Weidmann, Heinz A. Duerk, Harald Ballo, Martina Stauch, Juergen Barth, 

Axel Hinke, Wolfram Brugger, Study Group Indolent Lymphomas (StiL); Universitaetsklinik, Giessen, 

Germany; Klinikum Leverkusen, Leverkusen, Germany; Potsdam Klinikum, Potsdam, Germany; Outpatient 

Clinic, Cottbus, Germany; Onkologische Praxis, Neuss, Germany; Medizinische Hochschule Hannover, 

Hannover, Germany; Kreiskrankenhaus Lüdenscheid, Luedenscheid, Germany; Praxis Aschaffenburg, 

Aschaffenburg, Germany; Onkologische Praxis, Marburg, Germany; St. Bernward Krankenhaus, 

Hildesheim, Germany; Krankenhaus Nordwest, Frankfurt, Germany; St. Marien-Hospital Hamm, Hamm, 

Germany; Onkologische Praxis, Offenbach, Germany; Outpatient Department, Kronach, Germany; WisP 

Clinical Research Organisation, Langenfeld, Germany; Schwarzwald-Baar Clinic, Villingen- 

Schwenningen, Germany 

Background: This multicenter, randomized, phase III study compared B-R and CHOP-R as first-line 

treatment in indolent lymphoma and MCL and was presented at ASH 2009 including a comprehensive 

safety analysis. Here we present an updated analysis with a cut-off date for 31 Oct 2011. Methods: 549 

patients (pts) with indolent or MCL were randomized to receive B-R or CHOP-R for a max of 6 cycles. The 

primary endpoint was PFS. Results: 514 pts randomized pts were evaluable (261 B-R; 253 CHOP-R). 

Patient characteristics were well balanced between arms; median age was 64 years. At a median follow-up 

of 45 months, PFS was significantly prolonged with B-R compared with CHOP-R (HR 0.58, 95% CI 

0.44–0.74; P�0.001). Median PFS was 69.5 versus 31.2 months, respectively. The PFS benefit with B-R 

was maintained in all histological subtypes except marginal zone lymphoma. The PFS benefit with B-R was 

independent of age; HR 0.52 (P�0.002) in pts �60 years (n�199), and HR 0.62 (P�0.002) in pts �60 years 

(n�315). In pts with normal LDH (62%), PFS was significantly prolonged with B-R compared with 

CHOP-R (P�0.001), while in the elevated LDH group (38%) PFS was numerically, but not significantly 

increased with B-R compared with CHOP-R (P�0.118). In patients with follicular lymphoma, FLIPI 

subgroups defined by 0–2 factors (favorable) and 3–5 factors (unfavorable) had a longer PFS with B-R than 

with CHOP-R (P�0.043 and P�0.068 for the favorable and unfavorable FLIPI subgroups, respectively). 

Seventy four salvage treatments had been initiated in the B-R group; compared with 116 in the CHOP-R 

group, of those in the CHOP-R group 52 pts received B-R as salvage regimen. Overall survival did not differ 

between the treatment arms, with 43 and 45 deaths in the B-R and CHOP-R arms, respectively. Twenty 

secondary malignancies were observed in the B-R group compared with 23 in the CHOP-R group, with 1 

hematological malignancy in each group (1 MDS in B-R, 1 AML in CHOP-R). Conclusions: In patients 

with previously untreated indolent lymphoma, and elderly patients with MCL, B-R demonstrates a PFS 

benefit and improved tolerability compared with CHOP-R. 


GENITOURINARY CANCER 


Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone 

sensitive metastatic prostate cancer (HSM1PC) patients (pts): Results of S9346 

(INT-0162), an international phase III trial. 

Maha Hussain, Catherine M. Tangen, Celestia S. Higano, E. David Crawford, Glenn Liu, George Wilding, 

Stephen Prescott, Atif Akdas, Eric Jay Small, Nancy Ann Dawson, Bryan J Donnelly, Peter Venner, 

Ulka N. Vaishampayan, Paul F. Schellhammer, David I. Quinn, Derek Raghavan, Nicholas J. Vogelzang, 

Ian Murchie Thompson; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; SWOG 

Statistical Center, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA; University of 

Colorado Health Science Center, Aurora, CO; University of Wisconsin Carbone Cancer Center, Madison, 

WI; St. James University Hopsital, Leeds, United Kingdom; Marmara University, Istanbul, Turkey; 

University of California, San Francisco, San Francisco, CA; Georgetown Lombardi Comprehensive Cancer 

Center, Washington, DC; Prostate Cancer Institute, Calgary, AB, Canada; Cross Cancer Institute, 

Edmonton, AB, Canada; Karmanos Cancer Institute, Wayne State University, Detroit, MI; Urology of 

Virginia, Norfolk, VA; University of Southern California Norris Comprehensive Cancer Center, Los 

Angeles, CA; Carolinas Medical Center, Charlotte, NC; US Oncology Research, LLC, McKesson Specialty 

Health, The Woodlands, TX, and Comprehensive Cancer Centers of Nevada, Las Vegas, NV; University of 

Texas Health Science Center at San Antonio, San Antonio, TX 

Background: Castration resistance occurs in the vast majority of HSM1PC pts treated with AD, with a 

median survival of 2.5 years (y). It is in part an adaptive process with activation of genes resulting in the 

production of autocrine/paracrine growth factors that contribute to maintaining the viability of PC cells. 

Replacing androgens before castration resistance is hypothesized to maintain PC androgen-dependence. 

Preclinically IAD prolonged time to castration resistance and early clinical data indicated feasibility and 

potential for better quality of life. Methods: HSM1PC pts with performance status (PS) 0-2, PSA � 5 ng/ml 

were treated with 7 months (m) of goserelin � bicalutamide. Pts achieving PSA �4 ng/ml on m 6 and 7 

were stratified by prior neoadjuvant AD/finasteride, PS and disease extent (minimal, extensive) and 

randomized to CAD or IAD. Primary objective: To assess if overall survival (OS) with IAD is noninferior 

to CAD using a one-sided test with an upper bound hazard ratio�1.20, adjusting for stratification factors. 

Sample size: 756 pts/arm, type I and II error rates of 0.05 and 0.10. Results: 3,040 pts were accrued by 

SWOG, CALGB, ECOG, NCIC, and EORTC (5/95- 9/08). After 7 m of CAD, 1535 eligible pts achieved 

PSA �4.0 (median age 70 yrs, 4% PS 2, 48% extensive disease, 12% prior neoadjuvant AD) and were 

randomized to CAD (759 pts) or IAD (770 pts). Grade 3/4 related adverse events: IAD 30.3%, CAD 32.6%. 

Median follow-up was 9.2 yrs. Median and 10 yr OS: All eligible pts from study entry: 3.6 yrs, 17%; from 

randomization CAD: 5.8 yrs, 29%; IAD: 5.1 yrs, 23%, HR (IAD/CAD) � 1.09 (95% CI 0.95, 1.24). No 

interaction with therapy was significant (p�0.25) except suggestion with disease extent (p�0.08): extensive 

disease HR�0.96 (95% CI 0.79, 1.15, p�0.64); minimal disease: HR�1.23 (95% CI 1.02, 1.48, p�0.035). 

PC was cause of death in 56% of CAD and 64% IAD pts. OSby race was not different (p�0.44). 

Conclusions: In HSM1PC, IAD is not proven to be noninferior to CAD. For extensive disease pts IAD was 

noninferior; however, IAD was statistically inferior in minimal disease pts suggesting that CAD is the 

preferred treatment in this group. 



LBA506 Oral Abstract Session, Sun, 8:00 AM-11:00 AM 

Evaluation of lapatinib as a component of neoadjuvant therapy for HER2� operable 

breast cancer: NSABP protocol B-41. 

Andre Robidoux, Gong Tang, Priya Rastogi, Charles E. Geyer, Catherine A. Azar, James Norman Atkins, 

Louis Fehrenbacher, Harry Douglas Bear, Luis Baez-Diaz, J. Phillip Kuebler, Richard G. Margolese, 

William Blair Farrar, Adam Brufsky, Henry R. Shibata, Hanna Bandos, Soonmyung Paik, 

Joseph P. Costantino, Sandra M. Swain, Eleftherios P. Mamounas, Norman Wolmark; National Surgical 

Adjuvant Breast and Bowel Project and Centre Hospitalier de l’Universite de Montreal, Montreal, QC, 

Canada; NSABP Biostatistical Center and University of Pittsburgh Graduate School of Public Health, 

Department of Biostatistics, Pittsburgh, PA; National Surgical Adjuvant Breast and Bowel Project and 

University of Pittsburgh Cancer Institute, Pittsburgh, PA; National Surgical Adjuvant Breast and Bowel 

Project and University of Texas, Southwestern Medical Center, Dallas, TX; National Surgical Adjuvant 

Breast and Bowel Project and Kaiser Permanente, Denver, CO; National Surgical Adjuvant Breast and 

Bowel Project and SCCC-CCOP, Goldboro, NC; National Surgical Adjuvant Breast and Bowel Project and 

Kaiser Permanente Northern California, Vallejo, CA; National Surgical Adjuvant Breast and Bowel Project 

and Virginia Commonwealth University, Masey Cancer Center, Richmond, VA; National Surgical Adjuvant 

Breast and Bowel Project and CCOP San Juan, San Juan, PR; National Surgical Adjuvant Breast and 

Bowel Project and CCOP Columbus, Columbus, OH; National Surgical Adjuvant Breast and Bowel Project 

and Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, QC, Canada; National 

Surgical Adjuvant Breast and Bowel Project and Arthur G. James Cancer Hospital-Richard J. Solous 

Research Institute at Ohio State University, Columbus, OH; National Surgical Adjuvant Breast and Bowel 

Project and University of Pittsburgh, Magee-Womens Hospital, Pittsburgh, PA; National Surgical Adjuvant 

Breast and Bowel Project and McGill University Health Centre, Montreal, QC, Canada; NSABP 

Biostatistical Center, University of Pittsburgh, Graduate School of Public Health, Department of 

Biostatistics, Pittsburgh, PA; National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA; 

National Surgical Adjuvant Breast and Bowel Project Biostatistical Center and University of Pittsburgh 

Graduate School of Public Health, Department of Biostatistics, Pittsburgh, PA; National Surgical Adjuvant 

Breast and Bowel Project and Washington Cancer Institute, MedStar Washington Hospital Center, 

Washington, DC; National Surgical Adjuvant Breast and Bowel Project and Aultman Hospital, Canton, 

OH; National Surgical Adjuvant Breast and Bowel Project and Allegheny Cancer Center at Allegheny 

General Hospital, Pittsburgh, PA 

Background: The purposes of this trial are to determine the effect of substituting lapatinib (L) for 

trastuzumab (T) in combination with weekly paclitaxel (WP) following AC as well as adding L to T with 

WP following AC on pathologic complete response (pCR) rates. Methods: Women with HER2-positive 

operable breast cancer received standard AC q3wks x 4 cycles followed by WP (80 mg/m 2 ) on days 1, 8, 

and 15 q28 days x 4 cycles. Concurrently with WP, patients received either T (4 mg/kg load, then 2 mg/kg) 

weekly until surgery, L (1250 mg) daily until surgery, or weekly T plus L (750 mg) daily until surgery. 

Following surgery, patients received trastuzumab to complete 52 wks of HER2-targeted therapy. The 

primary endpoint is pCR breast. For each of the two primary comparisons, the Fisher’s exact test was used 

to test the equality of pCR rates. A Hochberg-type step-up procedure was applied to address multiple 

testings and to control the family-wise error rate at 0.05. Results: 51% were clinically node positive and 

63% had HR� tumors. pCR assessments were available from 519 of 529 patients. pCR percentage was 

52.5% for AC¡WP�T, 53.2% (p�0.9) for AC¡WP�L, and 62% (p�0.075) for AC¡WP�TL. pCR 

percentages in the HR� subset were 46.7%, 48% (p�0.85), and 55.6% (p�0.18), respectively, and were 

65.5%, 60.6% (p�0.57), and 73% (p�0.37) in the HR- cohort. The corresponding pCR breast and nodes 

percentages were 49.1%, 47.4% (p�0.74), and 60.4% (p�0.04). Grade 3/4 toxicities include diarrhea in 2%, 

20%, 27% (p�0.001), and symptomatic Gr 3/4 left ventricular systolic dysfunction in 4%, 4%, and 2% 

(p�0.49). Conclusions: Substitution of lapatinib for trastuzumab in combination with the chemotherapy 

program employed in this study resulted in similar high percentages of pCR in both HR� and HR- cohorts. 

Combined HER2-targeted therapy produced a numerically higher pCR percentage than single agent 

HER2-directed therapy, but the difference was not statistically significant. Central review of HER2 and ER 

is being conducted to determine if subsets benefiting from the combined HER2-targeted therapy can be 

identified. Funding: GlaxoSmithKline. 



LBA671 Oral Abstract Session, Sun, 8:00 AM-11:00 AM 

Open-label phase III randomized controlled trial comparing taxane-based chemotherapy 

(Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women 

with HER2� metastatic breast cancer: Interim analysis (IA) of NCIC CTG 

MA.31/GSK EGF 108919. 

Karen A. Gelmon, Frances Boyle, Bella Kaufman, David Huntsman, Alexey Manikhas, Angelo Di Leo, 

Miguel Martin, Lee Steven Schwartzberg, Susan Faye Dent, Susan Ellard, Katia Sonia Tonkin, 

Yasir M. Nagarwala, Kathleen I. Pritchard, Timothy Joseph Whelan, Dora Nomikos, 

Judy-Anne W. Chapman, Wendy Parulekar; British Columbia Cancer Agency-Vancouver Cancer Centre, 

Vancouver, BC, Canada; Mater Hospital, North Sydney, Australia; Chaim Sheba Medical Center, Tel 

Hashomer, Israel; British Columbia Cancer Agency, Vancouver, BC, Canada; City Clinical Oncological 

Dispensary, St. Petersburg, Russia; Sandro Pitigliani Medical Oncology Unit, Prato, Italy; Hospital 

Universitario Gregorio Maranon, Madrid, Spain; The West Clinic, Memphis, TN; The Ottawa Hospital 

Cancer Centre, Ottawa, ON, Canada; Cancer Centre for Southern Interior, Kelowna, BC, Canada; Cross 

Cancer Institute, Edmonton, AB, Canada; GlaxoSmithKline Oncology, Collegeville, PA; Sunnybrook Odette 

Cancer Centre, University of Toronto, Toronto, ON, Canada; Juravinski Cancer Centre at Hamilton Health 

Sciences, Hamilton, ON, Canada; NCIC Clinical Trials Group, Kingston, ON, Canada; NCIC Clinical 

Trials Group, Queen’s University, Kingston, ON, Canada 

Background: The relative efficacy of L vs T when combined with Tax chemotherapy in the first-line setting 

of metastatic breast cancer (BC) is unknown. Methods: MA.31 compares Tax-based therapy, paclitaxel 

80mg/m 2 wkly or docetaxel 75mg/m 2 3 wkly for 24 wks in combination with L or T. The L dose was 1,250 

mg po daily with Tax followed by 1,500 mg daily (LTax/L). After a loading dose, the T dose was 2 mg/kg 

wkly or 6 mg/kg 3 wkly � Tax followed by T 6 mg/kg 3 wkly (TTax/T). Stratification was by prior 

neo/adjuvant HER2 therapy, prior neo/adjuvant Tax, planned Tax (paclitaxel vs docetaxel), and liver 

metastases. The primary endpoint is ITT progression-free survival (PFS), defined as time from randomization 

to objective progressive disease based on RECIST criteria or death from any cause. The protocolspecified 

IA was performed after observing 333 PFS events; the trial was to stop if the 2-sided p-value from 

the stratified log-rank test was less than 0.03. The NCIC CTG’s independent DSMC reviewed IA results and 

recommended disclosure because the superiority boundary was crossed. A secondary analysis utilized 

central laboratory-confirmed HER2 � status. Results: Between July 17 2008 and Dec 1 2011, 652 pts were 

accrued. Data from 636 pts (525 HER2 centrally confirmed) were included in the IA with clinical cutoff date 

of Nov 7 2011 and database lock of Apr 13 2012. Median follow-up was 13.6 mos, 12.9 mos for LTax/L 

pts and 14.0 mos for TTax/T patients. In the ITT analysis, PFS was inferior with LTax/L compared to 

TTax/T hazard ratio (HR) �1.33; 95% CI 1.06-1.67; p�0.01. LTax/L had median PFS 8.8 mos (95% CI 

8.3-10.6) compared to TTax/T 11.4 mos (95% CI 10.8-13.7). PFS in the centrally confirmed HER2� had 

HR 1.48 (95%CI 1.15-1.92; p�0.003) (LTax/L to TTax/T). No difference in overall survival was detected 

(LTax/L to TTax/T) HR� 1.1 (95% CI 0.75-1.61; p�0.62). More grade 3-4 diarrhea and rash was observed 

with LTax/L (p�0.001). Conclusions: LTax/L therapy is associated with a shorter PFS compared to TTax/T 

as first line therapy for HER2� metastatic BC. ClinicalTrials.gov: NCT00667251. CCSRI grant: 021039. 

Supported by GlaxoSmithKline. 


GASTROINTESTINAL (COLORECTAL) CANCER 

LBA3500^ Oral Abstract Session, Sun, 9:45 AM-12:45 PM 

Bevacizumab (Bev) with or without erlotinib as maintenance therapy, following 

induction first-line chemotherapy plus Bev, in patients (pts) with metastatic colorectal 

cancer (mCRC): Efficacy and safety results of the International GERCOR 

DREAM phase III trial. 

Christophe Tournigand, Benoit Samson, Werner Scheithauer, Gérard Lledo, Frédéric Viret, Thierry Andre, 

Jean François Ramée, Nicole Tubiana-Mathieu, Jérôme Dauba, Olivier Dupuis, Yves Rinaldi, May Mabro, 

Nathalie Aucoin, Ahmed Khalil, Jean Latreille, Christophe Louvet, David Brusquant, Franck Bonnetain, 

Benoist Chibaudel, Aimery De Gramont, GERCOR; Hôpital Saint-Antoine, Paris, France; Hopital 

Charles-LeMoyne, Quebec, QC, Canada; Medical University of Vienna, Vienna, Austria; Hôpital Privé 

Jean Mermoz, Lyon, France; Institut Paoli Calmettes, Marseille, France; Pitie-Salpetriere Hospital, Paris, 

France; Centre Catherine de Sienne, Nantes, France; CHU de Limoges, Limoges, France; Centre 

Hospitalier Layné, Mont de Marsan, France; Clinique Victor Hugo, Le Mans, France; Hôpital Ambroise 

Paré, Marseille, France; Hôpital Foch, Suresnes, France; Cite De La Sante De Laval, Laval, QC, Canada; 

Hôpital Tenon, Paris, France; CICM/Charles LeMoyne Hospital, Longueuil, QC, Canada; Institut 

Mutualiste Montsouris, Paris, France; GERCOR, Paris, France; Centre Georges François Leclerc, Dijon, 

France; Hospital Saint Antoine, Paris, France 

Background: Therapy targeting VEGF or EGFR demonstrated clinical activity in combination with 

chemotherapy (CT) in mCRC but monoclonal antibodies cannot be associated. The DREAM trial compares 

a maintenance therapy (MT) with bev �/- EGFR tyrosine kinase inhibitor erlotinib (E) after a first-line 

Bev-based induction therapy (IT) in pts with mCRC. Methods: Pts with previously untreated and 

unresectable mCRC were eligible. After a Bev-based IT with FOLFOX or XELOX or FOLFIRI, pts without 

disease progression were randomized to MT between Bev alone (Bev 7.5 mg/kg q3w; arm A) or Bev�E (B 

7.5 mg/kg q3w, E 150 mg/day continuously; arm B). Pts were treated until progression or unacceptable 

toxicity. The primary endpoint was PFS on MT. Results: The study enrolled 700 pts from 01/2007 to 

11/2011 in 3 countries (France, Canada, Austria). 446 (63.7%) pts were randomized for MT (arm A, 

N�224; arm B, N�222). Among the 446 randomized pts, IT regimen was FOLFOX-Bev in 265 pts 

(59.4%), XELOX-Bev in 135 pts (30.3%), and FOLFIRI-Bev in 46 pts (10.3%). Baseline characteristics of 

randomized pts were (arm A/B): ECOG PS 0, 60% in both arms; normal LDH level 47%/49%; normal 

alkaline phosphatase level 48%/50%; synchronous metastasis 83%/82%. The median no of MT cycles was 

6 in both arms. With a median follow-up of 31.0 months, 327 PFS events were observed. Median MT-PFS 

were 4.6 m in arm A vs 5.8 m in arm B (HR 0.73 [95%CI: 0.59-0.91], P�.005). Median PFS from inclusion 

were 9.2 m vs 10.2 m. During MT, in arm A vs arm B, grade 3-4 diarrhea (�1% vs 9%) and grade 3 skin 

toxicity (0% vs 19%) were the main differences in toxicity. Severe adverse events from randomization 

related to B or E were 6 in arm A and 7 in arm B. Overall survival is not mature. Conclusions: The addition 

of erlotinib to bevacizumab after induction therapy significantly improves the duration of maintenance PFS, 

following induction with first-line chemotherapy plus bevacizumab, in patients with unresectable metastatic 

colorectal cancer. 



LBA3501 Oral Abstract Session, Sun, 9:45 AM-12:45 PM 

Results of the X-PECT study: A phase III randomized double-blind, placebocontrolled 

study of perifosine plus capecitabine (P-CAP) versus placebo plus 

capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer 

(mCRC). 

Johanna C. Bendell, Thomas J. Ervin, Neil N. Senzer, Donald A. Richards, Irfan Firdaus, 

A. Craig Lockhart, Allen Lee Cohn, Mansoor N. Saleh, Lesa R. Gardner, Peter Sportelli, Cathy Eng; Sarah 

Cannon Research Institute/Tennessee Oncology, Nashville, TN; Sarah Cannon Research Institute/Florida 

Cancer Specialists, Englewood, FL; Mary Crowley Cancer Research Center, Dallas, TX; Texas Oncology- 

Tyler, Tyler, TX; Sarah Cannon Research Institute/Oncology Hematology Care, Inc, Cincinnati, OH; 

Washington University School of Medicine , St. Louis, MO; Rocky Mountain Cancer Center, LLP, Denver, 

CO; Georgia Cancer Specialists PC, Sandy Springs, GA; Keryx Biopharmaceuticals, Inc., New York, NY; 

University of Texas M. D. Anderson Cancer Center, Houston, TX 

Background: Perifosine (P) is an oral, synthetic alkylphospholipid that inhibits or modifies signal 

transduction pathways including AKT, NFkB and JNK. A randomized phase II study examined P-CAP vs. 

CAP in pts with 2nd or 3rd line mCRC. This study showed improvement in mTTP (HR 0.254 [0.117, 0.555]) 

and mOS (HR 0.370 [0.180,0.763]). Based on these results, a randomized phase III study of P-CAP vs. CAP 

with a primary endpoint of overall survival (OS) in pts with refractory mCRC was initiated. Methods: The 

study was a prospective, randomized, double-blind, placebo-controlled randomized phase III trial. Eligible 

pts had mCRC which was refractory to all standard therapies. Pts randomized 1:1 to Arm A � P-CAP (P 

50 mg PO QD � CAP 1000 mg/m 2 PO BID d1-14) or Arm B � CAP (placebo � CAP 1000 mg/m2 PO 

BID d 1-14). Cycles were 21 days. Baseline tumor block collection and a biomarker cohort of pts with preand 

on-treatment tumor and blood samples were performed. Results: Between 3/31/10 and 8/12/11, 468 pts 

were randomized, 234 pts were in each arm. Baseline demographics were balanced between the arms: age 

� 65y (A: 65%, B: 58.5%), male (A: 57.7%, B: 53.0%), ECOG PS 0 (A: 39.7%, B: 39.7%), K-ras mutant 

(A: 50.4%, B: 51.3%), and median number of prior therapies (A: 4, B: 4). As of 3/19/12, median follow up 

was 6.6 months. Median overall survival: Arm A � 6.4 mo, Arm B � 6.8 mo, HR 1.111 [0.905,1.365], p 

� 0.315. Median overall survival for K-ras WT pts: Arm A � 6.6 mo, Arm B � 6.8 mo, HR 1.020 

[0.763,1.365], p � 0.894; K-ras mutant pts: Arm A � 5.4 mo, Arm B � 6.9 mo HR 1.192 [0.890,1.596], 

p � 0.238. Conclusions: Despite promising randomized phase II data, this phase III study shows no benefit 

in overall survival adding perifosine to capecitabine in the refractory colorectal cancer setting. Response 

rate, progression free survival, and safety data will be presented. Biomarker analysis is pending to see if 

subgroups of patients may have potential benefit. 



CRA3503 Oral Abstract Session, Sun, 9:45 AM-12:45 PM 

Bevacizumab (BEV) plus chemotherapy (CT) continued beyond first progression in 

patients with metastatic colorectal cancer (mCRC) previously treated with BEV plus 

CT: Results of a randomized phase III intergroup study (TML study). 

Dirk Arnold, Thierry Andre, Jaafar Bennouna, Javier Sastre, Pia J. Osterlund, Richard Greil, 

Eric Van Cutsem, Roger Von Moos, Irmarie Reyes-Rivera, Belguendouz Bendahmane, Stefan Kubicka; 

Hubertus Wald Tumor Center, University Cancer Center Hamburg (UCCH), Hamburg, Germany; Hopital 

Saint-Antoine, Paris, France; Institut de Cancerologie de l’Ouest/Site René Gauducheau, Nantes, France; 

Hospital Clínico San Carlos, Madrid, Spain; Helsinki University Central Hospital, Helsinki, Finland; IIIrd 

Medical Department with Hematology, Medical Oncology, Paracelsus Medical University Hospital 

Salzburg and AGMT (Arbeitsgemeinschaft Medikamentöse Tumortherapie), Salzburg, Austria; University 

Hospital Gasthuisberg, Leuven, Belgium; Kantonsspital Graubuenden, Graubuenden, Switzerland; Genentech, 

South San Francisco, CA; Roche, Basel, Switzerland; District Clinic Reutlingen, Department of 

Internal Medicine I, Reutlingen, Germany 

Background: BEV in combination with fluoropyrimidine-based CT is standard treatment for mCRC in the 

first-line (1L) and BEV-naïve second-line (2L) settings. This is the first randomized study evaluating the 

benefit of continuing BEV in combination with standard CT as 2L treatment for patients with mCRC who 

progressed after receiving a standard BEV-containing regimen in the 1L setting. Methods: Patients with 

unresectable, histologically confirmed mCRC who progressed within 3 months after discontinuation of 1L 

BEV � CT were randomised to 2L fluoropyrimidine-based CT � BEV (2.5 mg/kg/wk equivalent). Choice 

of oxaliplatin- or irinotecan-based 2L CT was dependent on the regimen used in 1L (crossover) and included 

as a stratification variable. The primary endpoint was overall survival (OS); secondary endpoints included 

progression-free survival (PFS), response rate and safety. Results: 820 patients were randomized from 

February 2006 to June 2010 (409 to BEV � CT and 411 to CT alone). Baseline patient and disease 

characteristics were well balanced between arms. The study met its primary endpoint; median OS was 11.2 

months for BEV � CT and 9.8 months for CT (HR�0.81; 95% CI 0.69–0.94; unstratified log-rank test, 

p�0.0062). Median PFS was 5.7 months for BEV � CT and 4.1 months for CT (HR�0.68; 95% CI 

0.59–0.78; unstratified log-rank test, p�0.0001). The response rate was 5.4% for BEV � CT and 3.9% for 

CT (unstratified Chi-Square Test, p�0.3113). The adverse event profile was consistent with previously 

reported data for BEV � CT. Compared with historical data from BEV treatment in 1L or 2L mCRC, 

BEV-related adverse events were not increased when continuing BEV beyond progression. Conclusions: 

This is the first randomized study to prospectively investigate the impact of continuing BEV treatment in 

2L mCRC for patients who progressed after receiving a BEV-containing regimen in 1L. Our findings 

demonstrate that BEV � CT (crossed over from 1L regimen) continued beyond progression significantly 

prolongs OS and PFS in 2L mCRC. Additional analysis (including biomarker evaluation) is ongoing. 


CRA6009 Clinical Science Symposium, Sun, 8:00 AM-9:30 AM 

Patterns of decision making about cancer clinical trial participation among the 

online cancer treatment community: A collaboration between SWOG and NexCura. 

Joseph M Unger, Dawn L. Hershman, Kenda Burg, Carol Moinpour, Kathy S. Albain, Judith A. Petersen, 

John Crowley; SWOG Statistical Center, Seattle, WA; Columbia University Medical Center, New York, NY; 

Nexcura, Seattle, WA; Fred Hutchinson Cancer Research Center, Seattle, WA; Loyola University Medical 

Center, Maywood, IL; Cancer Research and Biostatistics, Seattle, WA 

Background: Studies have shown an association between socioeconomic status (SES) and quality of 

oncology care, but less is known about the impact of SES on decision-making about CT participation. 

Methods: We assessed patterns of CT treatment decision-making according to important SES and 

demographic factors (age, sex, race, income, education) in a large sample of patients surveyed via a 

web-based treatment decision tool (NexCura, The Woodlands, TX). Eligible patients had a new diagnosis 

of breast, lung, colorectal, or prostate cancer, and were �18. Logistic regression (conditioning on type of 

cancer) was used. Reasons for non-participation in CTs were assessed using pre-specified items about 

treatment, family, cost, and logistics. All data were self-reported. Results: 5,499 patients were surveyed 

from 2007-2011. 40% discussed CTs with their physician; this differed by age (42% �65 v. 29% �65), 

income (42% �$50k/yr v. 36% �$50k/yr), and education (42% �college degree (CD) v. 37% �CD). 45% 

of discussions led to offers of CT participation, and 51% of offers led to CT participation. The overall CT 

participation rate was 9%, differing by age, income, and education (see table below). In a multivariate model 

including all SES and demographic factors (plus covariates comorbidity status and “distance to clinic”, a 

surrogate for convenience), income remained a predictor of CT participation (OR 0.73, 95% CI, 0.57-0.94, 

p�.01). Even in patients �65, who are nearly universally covered by Medicare, lower income predicted 

reduced CT participation (age by income interaction test, p�.05). Cost concerns were much more evident 

among lower income patients (p�.0001). Conclusions: Lower income patients were less likely to 

participate in CTs, even when considering age group.A better understanding of why income is a barrier may 

help identify ways to make CTs better available to all patients, and would increase the generalizability of 

CT study results across all levels of SES. 

Factor Category (code) % Enrolled in CT 

Age �65 (0) 

�65 (1) 

Income �$50k (0) 

�$50k (1) 

Education �CD (0) 

�CD (1) 

10.0 

5.4 

10.0 

7.6 

9.6 

7.9 

HEALTH SERVICES RESEARCH 

Odds ratio (OR) 

95% CI p value 

0.64 

0.48-0.85 

0.68 

0.54-0.86 

0.78 

0.64-0.96 

© 2012 American Society of Clinical Oncology. Reprinted with permission. 

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