Vol 24, No 18S Part I of II
`
`image, 2006
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`2006 ASCO Annual Meeting Proceedings
`
`42nd Annual Meeting
`June 2-6, 2006
`Georgia World Congress Center
`Atlanta, GA
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`www.]co.org
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`Offlclal journal of the American Society’ °f C""i°a' °"c°'°9y
`AS C®“ ’
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`~
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`A)/ENTIS EXHIBIT 2122
`Mylan v. Aventis, |PR2016-00712
`
`AVENTIS EXHIBIT 2122
`Mylan v. Aventis, IPR2016-00712
`
`
`

`
`42nd
`
`Annual Meeting of the
`
`American Society of Clinical Oncology
`
`June 2- 6, 2006
`
`Atlanta, Georgia
`
`2006 Annual Meeting Proceedings Part I
`
`(a supplement to the Journal of Clinical Oncology)
`
`
`
`Copyright 2006 American Society ofClinicz1l Oncology
`
`
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`

`
`Genitourinary Cancer
`
`2435
`
`General Poster Session (Board #63). Sun, 2:00 PM - 6:00 PM
`4806
`comparative expression profiling with kinetic RT-PGR in paired. fresh frozen
`and archived fomialln-fixed, paraffin-embedded renal cell cancer and normal
`tissue. G.~Ijenriig, H. Paus, D. Atkins, S. Storkel; Bayer Healthcare AG,
`Leverkusen, Germany; HELIOS Clinic, Wuppertal. Germany
`Background: It would be a substantial progress if gene expression of tumor
`markers could be accurately analyzed on RNA isolated from formalin fixed
`paraffin-embedded (FFPE) tumor tissue which is routinely collected. To
`prove equivalence between fresh frozen and archived FFPE tissue RNA
`profiles, we quantified 12 different genes with kinetic RT-PCR in renal
`tumor and paired adlacent normal tissue archived for 8-14 years. Methods:
`We had access to a set of 32 clear cell renal cell cancers and its adjacent
`normal tissue (H ELlOS Clinic, Wuppertal). Each sample existed as a FFPE
`tissue block and as paired fresh frozen tissue both stored over 8-14 years
`at RT or -80°C, respectively, RNA from FFPE tissue was isolated with a
`Bayer HealthCare internal silica bead—based isolation method. Each sample
`was analyzed with kinetic one—step RT-PCR for the gene expression of 3
`housekeepers (RPL37A, GAPDH, CD63) and 9 candidate genes (EGFR.
`Her2/neu, Her3, Her4, EGF, TGFa, NRG1, HlF1a, VEGFcx). Results: The
`comparative FFPEIfresh frozen expression data showed a good correlation
`over all data points (i = 0.87 for Ct values) and the tumor specific up and
`down regulation of EGFR family genes and its ligands could be detected in
`both tissue types equally. We could clearly demonstrate the tumor specific
`up-regulation of EGFR (2-fold). TGFai (2-fold). VEGFa (4-fold) and down-
`regulation of EGF (60-fold).
`iler2/neu (4-fold). Her3 (2-fold) and Her4
`(30-fold) in renal cell cancer for both tissue entities (fixed and fresh
`frozen).
`In addition a 3-dimensional Principal Component Analysis com-
`pletely separated the renal tumor population from paired normal tissue in
`both tissue entities based on the differential gene expression. Conclusions:
`Here we demonstrate that a small set of genes from the EGFR family and
`their ligands is specifically up-Idown-regulated in renal cell cancer tissue
`and therefore can be clearly distinguished from normal
`renal
`tissue.
`Furthermore. these data prove that the internal Bayer Heallhcare isolationl
`kinetic RT-PCR detection protocol
`for RNA from FFPE tissue allows
`accurate retrospective expression profiling and validation of marker panels
`in archived tissue material stored for more than a decade.
`
`4608
`
`General Poster Session (Board llGl5). Sun. 2:00 PM - 6:00 PM
`
`A phase II trial of docelaxel and samarium in patients with bone metastases
`from castration-refractory prostate cancer (GRPG) and a response or stabiliza-
`tion after induction docetaiiel-estramustine. A. Laglanche, P. Beuzeboc, J.
`Lumbraso, M. Di Palma, C. Theodore, D. Prapotnich, B. Escudler, J. Bauzy,
`V. Haddad. K. Fizazi; lnsritul Gustave Roussy. Vliiejulf, France; lnstitut
`Curie, Paris. France
`Background: Most patients (pts) with disseminated CRPC have bone
`metastases. Samarium is a radioisotope with a high affinity to bone.
`Docetaxel is currently the standard of care in CR PC. We assess the efficacy
`of combining docetaxel and samarium as consolidation treatment after
`docetaxel-estramustine in pts with CRPC. Methods: This is a prospective,
`bi-center phase II trial. Pts with bone metastases from CRPC received
`docetaxel 70 mg/m" day 2 + estramustine 10 mglKglday, day 1-5 (1 cycle
`every 3 weeks). Pts with a response or stabilization after 4 cycles were given
`consolidation therapy: docetaxel 20 mg/m2/week x 6 weeks + samarium 1
`injection during week 1 (37 MBqIKg). Zoledronic acid was routinely used
`and was stopped 1 month before samarium infusion. This study used a
`Simon two-step design with a final target of 39 pts receiving the consolida-
`tion treatment. Biological responses were defined according to the working
`group criteria (Bubley, J Clin Oncol 1999). The primary endpoint was
`progression-free survival lPFS). Results: From 01/2004 to 12/2005, 43 pts
`were included in the trial and the accrual is over. Of the 39 pts currently
`fully evaluable after induction treatment, 28 (72%). 10 (26%) and 1 (3%)
`achieved a PSA response, stabilization, and progression, respectively. Of
`30 pts currently evaluable after consolidation treatment, 20 (65%). 5
`(16%) and 5 (16%) achieved a PSA response, stabilization, and progres-
`sion, respectively. A pain response [defined as a decrease in pain intensity
`by at least 2/10 on a pain analog visual scale in pts with a baseline pain
`level 2 2/10) was achieved in 89% (16/18) after consolidation treatment.
`The consolidation docetaxel-samarium regimen was feasible with most pts
`experiencing a mild (grade 1-2) and rapidly reversible thrombocytopenia at
`week 5. Data on PFS and overall survival are pending. conclusions:
`Combining docetaxel and samarium is feasible and well-tolerated. it yields
`a high PSA response rate and a mayor pain improvement in pts with bone
`metastases from CR PC.
`
`General Poster Session (Board #64), Sun, 2:00 PM - 8:00 PM
`4607
`Multicenter, randomized, phase lll trial comparing radical relropliltic prostates-
`lomy with conventional external
`lleani radiotherapy for
`localized prostate
`cancer: An interim report. 8. M. Di
`tasl, A. Giannantonl, M. Valenti, L.
`Startl, F. Atflsani, T. Pallonr, E. A. Jannlni, M. Blbas, G. Zarnpa; Tor Vergata
`University. Rome, Italy; University at Perugra, Perugia, Italy; University of
`L‘AquiIa, L’Aqulla,
`lza/y,- Operative Unit of Urology, Sara (RR).
`Italy; 5.
`Filippo Nerl Hospital, Rome, ltaly; S. Giacomo Hospital, Rome, Italy
`Background: We report the outcomes of a randomised trial comparing
`radical retropubic prostatectomy (RP) with conventional external beam
`radiotherapy (EBRT) in patients with clinically localized prostate cancer.
`Methods: Between January 1997 and September 2001, 137 patients with
`clinically localized diagnosed prostate cancer were randomly assigned to
`RF in = 70) or EBRT in = 67). Data collected at follow-up included
`evidence of clinical disease progression, survival rates and general and
`disease specific health-related quality of life. All data were measured by
`physical examination, digital rectal examination, PSA, annual TC and bone
`scan and questionnaire, Analysis was by intention to treat. Results: After a
`median follow-up of 67 months (range 24~88) 35 patients (32.8%) had
`evidence of biochemical disease progression, 22 (31.4%) in RP group and
`23 (32.8%) in EBRT group respectively. The median time to biochemical
`failure was 55.5 months (range 1-86) in RP group and 56 (range 3~—88) in
`EBRT group. A local progression was observed in 11 patients (15.79°/o) of
`RP group and 12 (17.9%) of EBRT group. The median time to local
`progression was 65 months (range 6~86) in RP group and 64 (range
`6—88) in EBRT group. Distant metastases were observed in 4 patients
`(5.7%) in RP group and 6 (8.9%) in EBRT group. The median time to
`distant failure was 67 months (range 12~86) in RP group and 66 (range
`12-88) in EBRT group. Death due to prostate cancer occurred in 3/70 of
`patients assigned to RP (4.3%) and in 1/67 of those assigned to EBRT
`(1.5%). A significant decrease in general HRQOL was evident only in the
`first month after RP (p < 0.001). At 2 years, patients undergoing RP report
`significantly worse urinary function (p < 0.001), but better bowel function
`than those treated with EBRT (p < 0.001). Sexual dysfunction was more
`prevalent
`in the RP than in the EBRT group (70.2% versus 61.2%).
`Conclusions: This interim analysis indicates that there was no significant
`difference between RP and EBRT in terms of clinical disease progression
`and survival rates in patients with clinically localized prostate cancer.
`However, additional
`larger sample size accrual and long-term follow-up
`data are warranted to confirm these results.
`
`General Poster Session (Board #67). Sun, 2:00 PM — 8:00 PM
`4609
`Randomized phase II study comparing 4 monthly doses of ipllimumall (MDX-0(0)
`as a single agent or in combination with a single dose of dooetaiial in patients with
`homioiie-refractory prostate cancer. £_,_§mgl_l, C. Higano, N. Tchekmedyian, O.
`Sartor. B. Stein, R. Young, J. Vestal. W. Moseley, S Flschlroff.
`I. Lowy;
`University of Callfarnia. San Francisco, San Francisco. CA; Seattle Cancer Care
`Alliance, Seattle, WA; Pacific Shores Medi'cal Group, Long Beach, CA:
`Louisiana State University Health Sciences Center, New Orleans, M; Univer-
`sity Urologlcal Research Institute, Providence, RI; Grand Strand Urology,
`Myrtle Beach, SC; Urology Associates of North Texas, Arlington, TX; San Diego
`Urology Research, San Diego. CA; Medarex, lnc., Bloomsbury, NJ
`Background:
`ipilimumab is a fully human anti-CTLA-4 lgG1 monoclonal
`antibody that blocks CTLA—4 and augments immune responses. The current
`study evaluated the safety and activity of ipilimumab alone or with a single
`dose of docetaxel in hormone-refractory prostate cancer (HRPC). Methods: 43
`chemotherapy na'ive patients (pts) with HRFC, weretreated; 23 were in arm A
`(ipilimumab at 3 mg/kg q 4 weeks x 4 doses) and 20 in arm B (ipilimumab as
`in Arm A and one dose of 75 mg/m"’ of docetaxel on day 1). Results Six pts, 3
`in each arm, demonstrated a decrease in PSA of > 50%. Three pts. 2 in arm A,
`and 1 in arm B had confirmed PSA responses with durations of 79+ days,
`169+ days. and 280 days, respectively. There were no radiologic responses
`with these PSA responses. Thirty-six (84%) of the 43 pts experienced I or
`more adverse events considered to be related to treatment with ipilimumab.
`The most common adverse events included fatigue (44%). pruritus (26%).
`nausea (19%),
`rash (12%), constipation (12%), and weight
`loss (12%).
`Serious adverse events (SAEs) occurred in 18 patients (42%), who experi-
`enced 52 SAB. The majority (42 out of 52, 81%) were judged by the
`investigator to be unrelated or unlikely to be related to treatment with ipili-
`mumab. Five of the 52 SAEs reported in 3 pts were considered to be possible
`immune breakthrough events llBEs), associated with drug exposure and
`consistent with an immune-based mechanism of action. These were adrenal
`insufficiency (1), diarrhea, colitis, and melena (all in one patient) and colitis
`(1). One of these pts had a confirmed PSA response. Conclusions: ipilimumab
`was well tolerated in this group of pts with HRPC. Three pts overall (6%)
`experienced an IBE, a phenomenon that has been correlated in other studies
`with efficacy. ‘(here were several confirmed responses as assessed by PSA. one
`of which was correlated with an (BE. There was no apparent enhancement of
`activity by coadminlstration of a single dose of docetaxel. Further studies
`exploring ipilimumab in prostate cancer are warranted. either as monotherapy
`at higher doses, or in combination with immune modulatorsor vaccines.