`
`22nd Annual
`San Antonio
`
`Breast Cancer
`Symposmm
`
`DECEMBER 8-11, 1999
`
`SAN ANTONIO
`
`MARRIOTT RIVERCENTER
`
`101 BOWIE STREET, SAN ANTONIO, TEXAS 78205
`
`SPONSORED BY
`
`San Antonio Cancer Institute
`
`Cancer Therapy 8' Research Center
`and
`
`The University Of Texas Health Science Center
`at San Antonio
`
`CONFERENCE GRANTS FROM
`
`National Cancer Institute
`1R13 CA 83702-01
`and
`
`American Cancer Society
`
`InnOPharma Exhibit 1075.0001
`
`

`

`The San Antonio Breast Cancer Symposium
`is supported by educational grants from:
`
`BRISTOL—MYERS SQUIBB CO.
`ASTRAZENECA
`
`GENENTECH BIOONCOLOGY
`
`RHONE-POULENC RORER ONCOLOGY
`ROCHE LABORATORIES
`
`VYSIS INC
`
`GLAXO WELLCOME ONCOLOGY
`ELI LILLY 5' COMPANY
`PHARMACIA Er UPJOHN
`ALZA PHARMACEUTICALS
`MEDSCAPE
`ORTHO BIOTECH
`
`AMGEN
`CHIRON THERAPEUTICS
`DAKO CORPORATION
`DUPONT PHARMACEUTICALS
`HOECHST MARION ROUSSEL
`F HOFFMAN-LA ROCHE
`IMMUNEX CORPORATION
`LIPOSOME COMPANY
`NOVARTIS PHARMACEUTICALS
`SMITHKLINE BEECHAM ONCOLOGY
`VENTANA MEDICAL SYSTEMS
`
`Symposium Dates
`
`2000:
`2001:
`2002:
`2003:
`2004:
`
`December 6-9
`December 10-13
`December 11-14
`December 3-6
`December 8-11
`
`Abstract Submission Deadline: June 1 every year
`
`InnoPharma Exhibit 1075.0002
`
`

`

`25
`
`2
`
`RANDOMSED DOUBLE-BLIND PHASE 2 STUDY OF A SELECTIVE
`ESTROGEN RECEPTOR MODULATOR (SERM) LY353381 IN FATIENTS
`(Pts) WITH LOCALLY ADVANCED OR METASTATIC BREAST CANCER
`(LAMBC). Baselga J", Llornbart-Cussac A“. Bellet M'. Guillem—Porta v2,
`Petruzclka L3. ISaunas-in Vail D'Hebron. Barcelona 08036, Spain; 2Institutn
`Valencia de Oncologia, Valencia, 46009. Spain; ’ 1" Medical Faculty. Charles
`University, Prague. Czech Republic. 011 behalfot'the Study Group.
`LY353381 is a. new SERM which pro-clinical studies have shown to be a potent
`antagonist in breast and endornetrial models with beneficial agonist properties on
`boneandlipids. Weperfonned anase 2trialtoinvestigatc1he activityof
`LY353381 in LAMBC with randomisatioan 20 mg or 50 mg per day.
`Eligibility criteria included; Zubrnd PS of 0-1, estrogen andfor progesterone
`receptor positivity (ER/PR), adequate major organ filnction and no prior
`systmric therapy for LAMIBC Prior adjuvant tamoxifen (tam) was pemrirted
`provided it had stopped 2 12 months (mo) before study entry. Pts were stratified
`for prior tam. degree ofER positivity and the extent of metastatic involvement.
`Ninety—two pts were randomised between the two dose levels in a double-blind
`fashion and interim data is available on 87 pts Median age was 70 years (range
`37-94), vs 0 (55:37) and 1(32x37) with 7 pts pori- and so post-menopausaL
`Median time from diagnosis to study entry was lrno (range 0-251), 18/87
`received prior adjuvant chemotherapy and 31137 had adjuvant tam. Disease status
`at study entry was Locally Advanced (LA) in 31187 and 56f87 were classified as
`metastatic. Dominant disease sites were skin and sofl tissue (32/87), visceral
`(31/87), hone (16187) and node only (8187). Median time on therapy is currently
`3 mo (range 1-9 mo) andresponses havebeen seeninpts with MBC as well as
`those with LA disease only. The major side effect seen to date is hot. flushes with
`20/81 and 9181 patients with grade I or 2 severity, respectively. Other toxicities
`are minimal although lyrnphopenia has been noted in 13 patients (GI 3’81. G2
`Will and G3 LI‘SI). Whilst follow-up is limited, preliminary data on 55 patients
`currently evaluated at 3 mo include 10 confirmed PR5 (WHO criteria) in addition
`to [0 PRs and ZCRs needing 4 week confirmation Only 3 patients have been
`discontinued for PD before the 3 Inc Visit. LY353331 is also extremely well
`tolerated. Data analyses are ongoing and full, unblinded results between the two
`dose levels will be presented.
`
`Abstracts — General Sessions 31
`
`26
`
`EFFECT OF RALOXIFENE ON K167 AND APOP’I‘OSIS. Dowsctl M". Lu
`Y2, Hills M'. Bundred N3. Costa A‘, Decensi A‘, Sainsbury R5. O‘Brien M”, Scott T‘
`Muchmore DBZA 'Ruyal Marsden NHS Trust. London. England: 2Eli Lilly and Company.
`Indianapolis. IN; ’Whithington Hospital. Manchester. England; ‘European Institute of
`Oncology, Milan. Italy; ’I-Iuddersfreld Royal Infirmary. Huddersfield. England: “Mid Kent
`Oncology Centre. Maidstone. England.
`
`Ralnxifene (RLX) is a benzmhiophene selective estrogen receptor modulator (SERM) that
`has been approved in the US for the prevention of postmenopausal osteoporosis This
`double-blind study was performed to assess the effects of RLX on intermediate endpoint
`markers in human breast cancer. 167 postmenopausal women less than 80 years of age
`with a new diagnosis of stage I or ll primary breast cancer were randomly assigned to 14
`days of therapy with placebo. RLX 60 mgld or RLX 600 mgt'd. Baseline evaluation ofa
`core biopsy (at least l4 gauge needle) included measurement of K167. apoplosis. estrogen
`receptor (ER). and progesterone receptor (PR); these were repeated on tissue obtained from
`surgical resection of the primary tumor. I43 subjects (mean age, 66 years) had evaluable
`paired biopsy results. At baseline. 77% of subjeCLs had stage I disease and 83% had ER+
`tumors. Median percentage change from baseline to endpoint values are shown:
`Placebo
`RLX 60
`RLX 600
`NM
`N=50
`N:49
`+11%
`~15.4%*
`44.899
`Ki67
`+1 2.8%
`+20.0%
`0.00%
`Apoptosis
`710.4%
`42.59”
`328.0%‘
`ER
`4.7%
`3.6%
`78.4%
`PR
`*p<0.05 compared with placebo (ANOVA)
`Compared with placebo. KLX significantly reduced 1667 and ER but did not significantly
`affect apoptosis or PR levels. Both doses of RLX had modestly greater differences in
`K367 in the ER+ subset ofsubjects. These results are consistent with the previously
`reported safety profile of RLX in osteoporosis clinical trials, However. available clinical
`data do not suppon use of RLX in breast cancer treatment or nenadjuvant therapy
`
`PRELIMINARY RESULTS OF TWO Minn-CENTER TRIALS CDWARING THE
`EFFICACY AND TOLERABELITY 0F Amfixm (ANASTROZOlJ-I) AND
`TAMOXIFEN (TAM) IN POSMNOPAUSAL (PM) WOMEN WITH ADVANCED
`BREAST CANCER (ABC) Nablroltz I'M‘. Bounctcrre I. Buzdar AU. Thuerlimanrl
`BJK, Robertson JFK. Webster A. Steinberg M and van Euler M, on behalf of the
`'Arimidex’ Study Group. “ Cross Cancer Institute, Edmonton, Canada.
`'Arimidex‘ (AnaslmzoleXAN). a non-steroidal aromatase inhibitor is available for the
`treatment of ABC in PM women mn‘inglprogressing on TAM treatment. Two
`cliniml trials (carried out in USA I Canada [0030] and Europe I Rest of World [0027] J
`have compared the efi'icacy and tolerabilily of AN and TAM as firm-line therapies in
`PM women with ABC. The trials were designed to allow combination of the data. The
`results of trial 27 have been reported previously [see Table below for surrunary). Here
`we report the efi‘imcy results oftrial 0030 alone and the combined analyses of 0030 and
`0027. Both trials were randomized. double-blind. designed to demonstrate oquivflent
`efficacy anN 1 mg qd relative to TAM 20 mg qd in ER-we andfor PR+ve or unknown
`patients eligible for hormonal therapy (HT). The primary endpoints of the trial were
`time to propulsion (TIT), objective response (OR) and tolcnbility. The results for trial
`0030 and 0030:0027 are below:
`Study 0030. 353 patients entered the trial and were followed for a median of 1.8
`months. Disease progression (DP) was observed in 67% ofAN patients and 76% of
`TAM patients Median TT'P “as 11 months for AN and 5.6 months for TAM. 0R
`(CR+PR) m 21% and 17% for AN and TAM respecIiVer. Cliniorl benefit (CB) rates
`(CR+PR+SD 2 24 weeks) were 59% and 46% for AN and TAM respectively.
`A total M1021 palian {353 from 0030 and 668 from 0027). randomized on a ll]
`basis. were included in the combined analysis. DP was observed in 71% of AN patients
`and 76% of TAM patients. Median T'I'P ms 8.5 months for AN and 7 months for
`TAM. OR was 29% and 27% for AN and TAM respectively. C8 rates (CR+PR+SD 2
`24 weeks) were 57% and 52% for AN and TAM respectively.
`Est Value
`Lower 95% Cont Limit Equiv Criterion
`0027M3DlComb
`OOZTIOOBDIComb
`0.30
`Haz Ratio (Tl?) TAIWAN 0,99!1.44Il,11
`08611.16/100
`.m%
`Difi‘in R AN - 'r
`.
`- mourn/+17.
`- Wat—2w. 3%
`‘Arirnidu' satisfied the pre-defined criteria for equivalent efiilzq' to TAM in each trial,
`and the combined analysis, with there being a suggestion of a numerical advantage with
`respect to ‘ITP in the combined analysis and trial 0030. These data support the use of
`‘Arirnidex‘ as an alternative treatment to TAM in PM women with ABC.
`
`28
`
`A PARTIALLY-BLIND. RANDOMISED. MULTICENTRE STUDY
`COMPARING THE ANTI-TUMOR EFFECTS OF SINGLE DOSES (50,
`1%. AND 150 MG) OF LDNGACTING (LA) ‘FASLODEX’ (1C1 182.780)
`WITH TAMO)GFEN IN POGTMENOPAUSAL WOMEN WITH
`PRNARY BREAST CANCER PRIOR TO SURGERY. 'Robenson JFR,
`2Dixon M. ’Bundracl N “Anderson E. ’Dowsen M. sNicl-lolson R, 'Ellis 1. LCity
`Hospital. Nottingham, Western General Hospital, Edinburgh. 3South
`Manchester University Hospital, Mamhester, “Christie Hospital. Manchester.
`sRoyal Marsden. London. “University College of Medicine. Cardiff, Wales.
`UK.
`
`'Faslodex' (ICI 182.780) is the most advanced of a new class of drugs. the
`non-agonisr (‘pure'). steroidal anti-estrogen. currently in clinical trials in
`postmenopausal women with advanced breast cancer. Here. we report on the
`design of a partially-blind. modernised. multicentre study to compare the anti-
`turmr effects [upon estrogen receptors (ER). progesterone receptors (PR). 67
`and apoploric index [AU]. tolerability. and pharmacokjnerics (PK) of LA.
`single-doses of ICI 182,780 (50 mg, 125 mg. and 250 mg) given
`intramuscularly (i.m) with tamoxifen and tarmx'rfnrl placebo in postmenopausal
`women prior to surgery for primary breast cancer.
`Two hundred postmenopausal women with primary breast cancer
`(Tl—T3; Eli-positive or ER-unlcnown tumor) awaiting curative-intent resection
`surgery were recruited to the study. Patients had no prior ueatrrrent with
`tarmxifen. any other anti-hun'mnal therapy. radiotherapy, or madjuvarlt
`chemotherapy for breast cancer; Urey were randomised (n: 40 per treatment
`arm) to receive a single i.m dose ofICI 18178060. 125. or 250 mg). or oral
`tamoxifen [20 mg once daily) or watching tamoxifen placebo for l4 to 2] days.
`Biopsy samplm, taken pro-treatment from the tumor and on the day of surgery
`(performed between days 15 and 22 ofrhe study), were assessed for ER. PgR.
`1667. and AL The PK profile was assessed at each dose level on Days I, 3. 8.
`ll. 15. 22 . 29. 36. 43. 57. and 85. This study was designed as an exploratory
`trial. so the minimum power for statistical testing was set at 80% using a two-
`sided significance level of 5%. powered to detect differences in the tumor
`rmrkers (ER, PgR. Ki67. and A1). and the lolerability and PK profiles The
`findings of this study will be reported,
`‘Faslodex’ is a trade mark. the property ofZeneca le. a pan of Astrame
`
`InnoPharma Exhibit 1075.0003
`
`