`
`22nd Annual
`San Antonio
`
`Breast C_ancer
`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-O1
`and
`
`American Cancer Society
`
`|nnOPharma Exhibit 10750001
`
`

`

`The San Antonio Breast Cancer Symposium
`is supported by educational grants from:
`
`BRISTOL—MYERS SQUIBB co.
`ASTRAZENECA
`
`GENENTECH BIOONCOLOGY
`
`RHONE-ROULENC RORER ONCOLOGY
`ROCHE LABORATORIES
`
`GLAXO WELLCOME ONCOLOGY
`ELI LILLY 8 COMPANY
`PI-IARMACIA 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
`VYSIS INC
`
`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
`
`|nnoPharma Exhibit 1075.0002
`
`

`

`25
`
`2
`
`RANDOMISED DOUBLE-BLIND PHASE 2 STUDY OF A SELECTIVE
`ESTROGEN RECEPTOR MODULATOR (SERM) LY35338l IN PATIENTS
`(Pts) WITH LOCALLY ADVANCED OR METASTATIC BREAST CANCER
`(LAMBC). Baselga J‘-, Llornbart-Cussac A‘, Bellet M‘, Guillern-Porta V‘,
`Petruzellra L’. ‘sanremia Veil D'I-lebron, Barcelona 03035, Spain; zlnstituto
`Valencia de Oneologia, Valencia, 46009, Spain; ’ 1" Medical Faculty, Charles
`University, Prague, Czech Republic. On behalfoftlte Study Group.
`LY35338l is a new SERM which pre-clinical studies have shown to be a potent
`antagonist in breast and endometrial models with beneficial agonist properties on
`boneandlipids. Weperformed al’hase Ztlialtoinvestigatethe activityof
`LY35338l in LAMBC with randomisationbetween 20 mg or 50 mg per day.
`Eligibility criteria included; Zubrod PS of 0-1, estrogen andfor progesterone
`receptor positivity (ERIPR), adequate major organ function and no prior
`systo-nic therapy for l..A.MBC, Prior adjuvant tamoxifen (tam) vms permitted
`provided it had stopped 2 12 rnonths (mo) before study entry. Pts were stratified
`for prior tam, degree ofER positivity and the extent of metastatic involvement.
`Ninety—tvvo 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(32xs7) with 7 pts peri- and so pos‘l-menopausal.
`Median time from diagnosis to study entry was lrno (range 0-251), 18/87
`received prior adjuvant chemotherapy and 31'8".’ had adjuvant tam, Disease status
`at study entry was Locally Advanced (LA) in 31187 and 561%? were classified as
`metastatic. Dominant disease sites were skin and sofl tissue (32/87), visoeral
`(31/E7), bone (1 6187) and node only (8187). Median time on therapy is currently
`3 mo (range l-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 1 or 2 severity, respectively. Other toxicities
`are minimal although lymphopenia has been noted in 13 patients (G1 5.’8l, G2
`"Hill and G3 U81), 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 PR5 and 2CRs needing 4 week confirmation. Only 3 patients have been
`discontinued for PD before the 3 mo visit. LY353381 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 APOPTOSIS. Dowsctl M", Lu
`Y’, Hills M‘, Bundred N‘, Costa A‘, Decensi A‘, Sainsbury R’. O'Brien M”, scou T1‘
`Muchmore DB‘. 'Ruyal Marsden NHS Trust, London, England: ‘Eli Lilly and Company.
`Indianapolis. IN; ’Whithington Hospital. Manchester, England; ‘European Institute of
`Oncology, Milan. Italy; ‘Huddersfield Royal Infinnary, Huddersfield, England: "Mid Kent
`Oncology Centre, Maidstone, England.
`
`Ralnxifene {RLXJ is a benzorlriophene selective estrogen receptor modulator (SERM) that
`has been approved in Lhe US for the prevention of posu-nenopausal osteoporosis. This
`double-blind study was performed to assess the effects of RLX on intermediate endpoint
`markers in human breast cancer. 16'.’ postmenopausal women less than 80 years of age
`with a new diagnosis of stage I or H primary breast cancer were randomly assigned to 14
`days of therapy with placebo, RLX 60 mgld or RLX 600 mgfd. Baseline evaluation ofa
`core biopsy (at least I4 gauge needle) included measurement of K.i6':', apoptosis, estrogen
`receptor (ER), and progesterone receptor (PR); these were repeated on tissue obtained from
`surgical resection of Lhe primary tumor. I43 subjects (mean age, 66 years) had evaluable
`paired biopsy results. At baseline, 77% of subjecu had stage I disease and B3% had ER+
`tumors. Median percentage change from baseline to endpoint values are shown:
`Placebo
`RLX 60
`RLX 600
`N%
`N=50
`N=49
`+5.l%
`~15.4%*
`Al4.89l:*
`Ki6'.7
`-7-12.8%
`+2D.0%
`0.00%
`Apoptosis
`40.4%
`~22.5%*
`28.0%‘
`ER
`-2.7%
`-3.6%
`—8.4%
`PR
`*p<0.05 compared with placebo (ANOVA)
`Compared with placebo. RLX significantly reduced Kid? and ER but did not significantly
`affect apoptosis or PR levels. Both doses of RLX had modestly greater differences in
`Kid? 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 support use of RLX in breast cancer treatment or nenadjuvant therapy,
`
`PRELIMINARY RESULTS OF TWO MU1.'l'l-CENTER TRIALS COMPARING Ti-l'E
`EFFICACY AND TOLERABELITY OF AR]MlDEXm (ANASTROZOLE) AND
`TAMOXII-‘EN (TAM) IN POS'I'MENOPAUSAL (PM) WOMEN WITH ADVANCED
`BREAST CANCER (ABC). Nablroltz TM‘, Borrneterre l, Buzdar AU, Tlruerlimanrr
`BJK, Rnberrson JI-‘R, Webster A, Steinberg M and van Euler M, on behalf of the
`'Arirnid:x’ Study Group. “ Cross Cancer Institute, Edmonton, Canada.
`'Arimldex‘ (anaslmzolc)(A.N'), a nun-steroidal aroruatnse inldbitor is available for the
`treatment of ABC in PM women recurr'ingi'progrr.ssing on TAM treatirtent. Two
`clinical trials (carried out in USA I Canada [0030] and Europe I Rest of World [0027] )
`have compared the efifioaey and toicrabiliry of AN and TAM as first-line therapies in
`PM women with ABC. The trials were designed to allow combination of the data. The
`results of trial 2‘! have been reported previously [see Table below for surrunaty). Here
`we report the efiimcy results oftrial 0030 alone and the combined analyses of 0030 and
`0027. Both trials were raridornizod, double-blind, designed to demonstrate oquivflcnt
`effioaey oI'AN l mg qd relative to TAM In mg qd in l.=.R-we andlor PR+ve or unknovm
`patients eligible for hormonal therapy (HT). The primary endpoints of the trial were
`Lirnc to pro-pension (TTP), objective response (OR) and toleiability. The results for trial
`0030 and OOSOIOOZT 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 TTP was 11 months for AN and 5.6 months for TAM. OR
`(CR+PR) wu 21% and 17% for AN and TAM respectively. Cliniml benefit (CB) rates
`(CR-l'PR+SD 2 24 weeks) were 59% and 46% for AN and TAM respectively.
`A total of 1021 patient (353 from 0030 and 668 from 0027), rarrdornized on :2 EJ
`basis, were included in the combined analysis. DP was observed in 71% of AN patients
`and 76% of TAM patients. Median TTP was 8.5 months for AN and ‘I months for
`TAM. OR was 29% and 27% for AN and TAM respectively. C8 rates (CR+PR+SD 2
`24 weelrs) were 57% and 52% for AN and TAM respectively.
`Est Value
`Lower 95% Card Limit Equiv Criterion
`DD2T.f003D.'Comb
`0O2'r'./0030n'COmb
`0.80
`l-IazRar.io (Tl?) TAMIAN 0,99.'l.-l4n'l,l1
`D,86.'l.lfi/1.00
`-l()%
`Difiin R AN -T
`-
`-1%‘-l-$%:‘+l‘Vn
`- 7“/.'-2%f- 3%
`‘Arirrriduf satisfied the pre-defined criteria for equivalent elfczqv 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
`‘A.rirn.idex‘ as an altenrative Lreatrnent 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 LDNGACTIING (LA) ‘FASLODEX’ (ICI 182,780)
`WITH TAMO)flFEN IN POGTMENOPAUSAL WOMEN WITH
`PRTMARY BREAST CANCER PRIOR TO SURGERY. 'Rober1son JFR,
`2Dixorr M. ’Bundred N ‘Anderson E. ‘Dome: M. "Nicholson R, 'E|l':s 1. “city
`Hospital, Nottingham, iwestem General Hospital, Edinburgh, ’South
`Manchester University Hospital, Manchester, ‘Christie Hospital, Manchester,
`‘Royal Marsden, London, “University College of Medicine, Cardiff, Wales,
`UK.
`
`'Fa.slodex' (ICI 182,780) is the most advanced of a new class of drugs, the
`non—agorris1[‘pure'). steroidal anti-estrogens, currently in clinical trials in
`postrrrenopausal worrren with advanced breast cancer. Here, we report on the
`design of a partially-blind. randomised, multicerrtre study to compare the anti-
`turmr effects [upon estrogen reoeptors (ER), progesterone receptors (PR), 67
`and apoproric index [A1]], tolerability, and pharnracokirieiics (PK) of LA.
`single-doses of ICI 182,780 (50 mg, l25 mg, and 250 mg) given
`intramuscularly (i.m) with tamoxifen and tarnoxifen placebo in postrneoopausal
`women prior to surgery for primary breast cancer.
`Two hundred postmenopausal women with primary breast cancer
`(Tl—T3; ER—positive or ER—unlcnown tumor) awaiting eurative—in1enI resection
`surgery were recruited to the study. Patients had no prior Lreatrrrent with
`tamoxifen, any other anti-hurrrrunal therapy, radiotherapy, or netradjuvant
`chernotherapy for breast cancer; may were randomised (n: 40 per treatment
`arm) to receive a single i.m dose ofICI 182,780 (50, 125, or 250 mg), or oral
`tamoxifen [20 mg once daily) or rmtching tamoxifen placebo for I4 to 2] days.
`Biopsy saroplm, taken pro-trearrnent from the tumor and on the day of surgery
`(performed between days 15 and 22 ofrhe study), were assessed for ER, PgR,
`Ki6'.’, and Al. The PK profile was assessed at each dose level on Days I, 3, 8,
`ll, 15,22 , 29, 36, 43, 5'1‘, 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, Ki6'.', and AD, and the lolerability and PK profiles The
`findings of this study will be reported,
`‘Faslodex’ is a trade mark, the property ofZeneca Ltd, a pan of AsLra2.erirx;a
`
`|nnoPharma Exhibit 10750003
`
`