`
`PENGAD000-831-6069
`
`EXHIBIT
`
`2075
`
`THIRTY-FOURTH
`Annual Meeting of the
`American Society of Clinical Oncology
`May 16 - 19, 1998
`PROGRAM/PROCEEDINGS
`Los Angeles, California
`
`
`
`Contents
`
`ASCO Program Information
`iii
`Officersand Directors... 1...ke ec eee eet et ee ree eet eens
`iv
`Calendar ofEvents 2.0... cee ee ent ee ee eee renee etree reese
`xi
`Committee Rosters 2...ee eee ene nee eee eee
`xai
`General Information .... 0.0.20... 06 ccc ee ee ee eee eee eee eens
`xvi
`Award Recipients 2.0.00.et eee te eee teens
`xvii
`1998 ASCO MeritAwards... tee ene tee ene e een ees
`xviii
`Plenary Session... 000.ete tener ete eenaes
`xix
`Integrated Symposia... eet ee ee tee eter b beet eens
`x
`Special Sessions .. 0... ec ee ee eee eee een e eae
`Annual Business Meeting... 10... 2. ee tee eee eee xxii
`TumorPanel Sessions .. 1... ee eee eee ete een ene nee e nes
`xxiv
`Scientific Symposia . 6...ee ee eee eee xxvii
`Education Sessions 2.0 eet eee eee teen ee nee eens xxviii
`Meet the Professor Session8 «0.1... ete ee cee eet neeeeenee soodii
`1998 Annual Meeting Support... 0...et eet ete entre ee eneeeaee rocxvil
`1998 ASCO Exhibitor List... 0.ee ne teen teen eee teeees xocxviii
`ASCO Shuttle Service... eee ene ete ete e ete eeene
`xl
`Los Angeles Convention Center Maps... 1.0.0.0... 00 ccc cee eee ee eee teens xiii
`Scientific Program 2.0.6... ee ee eee eee eee en eee eee
`xiv
`ASCO Proceedings .. 26... eee eee ene eee eee eee
`la
`Plenary Session... 2... een ee teen eee nett een eeeees
`la
`Adult Leukemia andLymphoma ... 1... 0... ee eee etree ee enne
`2a
`AIDS/SupportiveCare...ee eee eee teeta ee
`4la
`Bone Marrow Transplantation/Cytokines .. 10... 0... ce ee ee ete e eens
`75a
`Breast Cancer... 2.0 eee eee ee ete bebe ee enees
`97a
`Clinical Pharmacology... 2... 0. eee eee ee eee eee tebe nee nees
`185a
`Gastrointestinal Cancer... 1... ee ee eee eee beeen teen nae eeeens
`255a
`Genitourinary Cancer . 0... 1. ee eet eee eee eee eee rene teennees
`807a
`Gynecologic Cancer 6.0.0... eee tee eaten ent e en neee
`349a
`Head and Neck Cancer and CNS .... 2... ee ene eee n ee eeees
`378a
`Health Services... 0... ee eee ee eee nee e eee e eens neees
`413a
`Immunobiology and Biologic Therapy... . 20... 0.0000. ccc ccc eee e ene ene eee eben eee enes
`428a
`Lung Cancer... 2... ee eee eee eee
`ao ue cee eee ee eee eee
`460a
`PediatricOncology....... 2.0.0.0 .0 0c eeee 30
`a
`33ui fh See eens 525a
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`Melanoma and Sarcoma................2000- meauso4| UB ee 505a
`Tumor Biology/Human Genetics................ G98Me eee. 547a
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`(cid:43)(cid:82)(cid:86)(cid:83)(cid:76)(cid:85)(cid:68)(cid:3)(cid:89)(cid:17)(cid:3)(cid:42)(cid:72)(cid:81)(cid:72)(cid:81)(cid:87)(cid:72)(cid:70)(cid:75)
`Hospira v. Genentech
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`IPR2017-00805
`(cid:42)(cid:72)(cid:81)(cid:72)(cid:81)(cid:87)(cid:72)(cid:70)(cid:75)(cid:3)(cid:40)(cid:91)(cid:75)(cid:76)(cid:69)(cid:76)(cid:87)(cid:3)(cid:21)(cid:19)(cid:21)(cid:24)
`Genentech Exhibit 2025
`
`1
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`

`

`192a
`
`CLINICAL PHARMACOLOGY
`
`CLINICAL PHARMACOLOGY
`Clinical Pharmacology tl
`General Poster Session, Tuesday, May 19, 1998
`
`*739
`A PHASE | AND PHARMACOKINETIC (PK) STUDY OF DOCETAXEL IN CANCER
`PATIENTS (PTS) WITH LIVER DYSFUNCTION DUE TO MALIGNANCIES.S.D.
`Baker, P. Ravdin, C. Aylesworth, L. Smetzer, R. Bruno, L. Vernillet, R.
`Pazdur, G. Doyle, L. Hammershaimb, E. Hooker, H. Burris, G. Eckhardt, T.
`Johnson, M. Kraynak, L. Hammond, G. Rodriguez, G. Weiss, D. Von Hoff, &
`E. Rowinsky. Cancer Therapy & Research Center, San Antonio, TX. MD
`Anderson, Houston, TX and Rhone-Poulenc Rorer, Collegeville, PA &
`Antony, France.
`Docetaxel, a semisynthetic taxoid, undergoes extensive metabolism by
`cytochrome P-450 3A4 andbiliary excretion. In phase II trials, a popula-
`tion PK evaluation revealed that pts with elevated alkaline phosphatase
`(AP) (>2,5 ULN) and SGOT and/or SGPT (> 1.5 ULN) had a 30% decrease
`in mean docetaxel clearance which was associated with an increased risk of
`severe toxicity (Proc. ASCO 14:457;1995). This study was performed to
`determine the MTD and PKprofile of docetaxel in cancer pts with varying
`degrees of tumor-related liver impairment. Pts were enrolled into one of 3
`groups:
`(1) Tbili =1.5 to <3.0 ULN with any AP and transaminase
`elevation, (2) Tbili =3.0 ULN with any AP and transaminase elevation, and
`(3) Tbili = 1.0 ULN with elevated SGOT and/or SGPT (>1.5 to =5.0 ULN)
`and AP(>2.5 to <5.0 ULN). The starting dosefor all groups was 40 mg/m?
`(1 hr infusion) every 3 weeks. To date, 13 patients, 11 of whom haveliver
`metastases, were treated with 30 courses at 40 mg/m2 (3 pts each in
`groups 1 and 2, and 1 ptin group 3) and 60 mg/m:(3 pts each in groups 1
`and 2). Docetaxel 40 mg/m? was well tolerated bypts in all groups. At 60
`mg/m?, DLT occurred in 1 ptin group 1 (ANC < 500/,Lwith infection) and
`2 pts in group 2 (gr 3 mucositis), although 1 of these pts received prior RT
`to the external biliary ducts and was replaced. Pt accrual has been
`expanded at 60 mg/m?for groups 1 and 2. A 3-compartmentlinear model
`was used to determine the following preliminary PK estimates:
`No.of
`Dose
`Cmax
`AUC
`cl
`
`Group
`Pts
`(mg/m2
`(pe/ml)
`(ye*hr/mL)
`(Uhr/m2
`1
`2
`40
`1.5, 1.7
`2.4,6.2
`16.8,6.5
`1
`60
`3.9
`7.6
`7.9
`2
`40
`0.69, 1.4
`1.1, 2.3
`37.7,17.1
`2
`60
`3.1,3.7
`6.1,6.7
`9.8, 8.9
`1
`40
`1.3
`2.7
`15.0
`
`2
`
`3
`
`in the majority of patients in groups 1 and 2, higher AUC values were
`observed at 60 mg/m? than 40 meg/m?, which may have contributed to
`differences in toxicity at the 2 dose levels. In these patients, AUC values
`achieved at 60 mg/m? appear to be similar to those at 100 mg/mZ2in
`patients with normal liver function parameters (J. Clin. Oncol. 13:2643;
`1995).
`
`Proceedings of ASCO Volume 17 1998
`
`*740
`LONG-TERM WEEKLY PACLITAXEL (P) IN METASTATIC BREAST CANCER (MBC).
`
`A PHASE[1 TRIAL IN PRETREATED PATIENTS (PTS). S. Breier, C. Lebedinsky,
`C. Ayiviri, C. Roffé, G. Traine, C. Cot, P. Politi. Hospital Israefita, Buenos
`Aires, Argentina.
`é
`Long-term therapy with short infusions of P is limited by myelosuppression
`and cumulative neurotoxicity. In order to allow prolonged treatment with P
`in pts with MBC, the activity and toxicity of a weekly infusion of P was
`studied. Twenty-four ambutatory pts with measurable MBC, previously
`treated with chemotherapy (5 pts adjuvant. 7 pts neoadjuvant, 18 pts
`metastatic) received P (80 mg/m2 over 1 hr) every week until disease
`progression orlimiting toxicity. Dexamethasone 4 mg, diphenhydramine 30
`mg, and ranitidine 50 mg were given i.v. immediately prior to each dose of
`P. EMG and neuro exam were performed at baseline andatleast every 6 and
`3 months, respectively. All pts gave written informed consent. Pts charac-
`teristics were: median age: 55 (35-77), PS: O-2, pre/postmenopausal:
`10/14 pts. Sites of metastatic disease (%) included liver (25), bone (38).
`lung (46) and soft tissue (50). Number of metastatic sites: 1 (50%), 2
`(29%), 3 or more, (21%). A total of 595 weekly doses were delivered, with
`a median of 25 doses per pt (5-55). Median cumulative dose was 1980
`mg/m2 (400-4400), median delivered dose intensity: 78 mg/m2fwk
`(72-80), 97% of planned. The overall response rate was 12/24 (50%, 95%
`Cl: 30-70), CR: 2/24 (8%), PR: 10/24 (42%), SD: 5/24 (21%), PD: 7/24
`(29%). Median timeto progression: 9 months (2-18), median survival: 17
`months (2-25). Toxicity (NCI criteria): No Grade 4 toxicity was observed.
`Grade 3 WBC: 1 pt. The mean granulocyte nadir was 1783/uL (1078-
`2970). No febrile neutropenia, no septic deaths. One admission due to
`DVT. There was no Grade 3-4 nonhematologic toxicity, except alopecia (9
`pts, 38%). Onycholysis/onychomycosis was noted in 7 pts (29%), skin rash
`in 2, Grade 1 nausea in 3 (13%). No major hypersensitivity. The worst
`neuropathy was Grade 2 (4 pts). EMG showed axonopathy in 5 pts.
`Concusions: Long-term weekly P is active and well tolerated in MBC. This
`schedule allows a high cumulative dose of P without major myelo- or :
`neurotoxicity. This weekly regimen deserves further exploratian.
`
`*741
`DEPOSITION OF PACLITAXEL INTO NORMAL AND MALIGNANT BRAIN TUMOR
`TISSUE. #.L. Fine, C. Baimaceda, J. Bruce, J. Hall, C. Hesdorffer, M. Sisti,
`M. Huang, M_R. Feteil. Columbia University College of Physicians and
`Surgeons, New York, NY.
`In vitro, paclitaxel demonstrates marked antitumoractivity against human
`glioblastoma cet! tines. However, in vivo paclitaxel has minimal activity
`against newly-diagnosed glioblastoma (Fetel! et al: J Clin Oncol 15:3121-
`3128, 1997). One possible explanation is poor paclitaxe! deposition into
`the brain tumor because of
`the blood brain barrier
`(BBB) and P-
`glycoprotein (Pgp). Our preclinical studies in rats bearing C6 gliomas
`demonstrated that a Pgp inhibitor, tamoxifen, increases the deposition of
`paclitaxel into rat brain tumors by as much as 400%.
`In our clinical studies, we treated patients with recurrent primary brain
`tumors or brain metastases who required surgical resection as the next
`appropriate treatment. Six patients received paclitaxel 175 mg/m? between
`12 to 18 hrs prior to resection; three of these patients also received high
`dose tamoxifen. At surgery, samples of tumortissue (T), brain adjacent to
`tumor (BAT), normal brain (NL), and serum were measured by reverse
`phase HPLC for paclitaxel and tamoxifen. Mean tissue paclitaxel levels
`(ng/g) for T were 1078 (187-2135), BAT 739 (36-2116) and NL 362
`(42-945). Mean serum paclitaxel
`leveis (ng/ml) at surgery were 90.4
`(47-165). There was no increase in paclitaxel tissue fevels in patients who
`received tamoxifen, however serum levels were 2.1 mM (1.1-3.2), below
`the therapeutic level for Pgp inhibition.
`These preliminary data suggest that paclitaxe| penetrates and accumulates
`in brain tissue in the following order: T > BAT > NL. Conclusions about
`tamoxifen's effectiveness for increasing pactitaxe! penetration into brain
`tumors arestill being assessedutilizing higher tamoxifen doses.
`
`2
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