Thirty-Fifth
`Annual Meetingof the
`AmericanSociety of Clinical Oncology
`May15-18, 1999
`Atlanta, Georgia
`Program/Proceedings
`
`
`
`Copyright 1999 American Society of Clinical Oncology
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`3
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`f 203)
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`Hospira v. Genentech
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`IPR2017-00805
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`Genentech Exhibit 2031
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`

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`126a
`
`*479
`
`BREAST CANCER
`
`Sentinel Node Biopsy Using a Non-Blue Dye Technique: Results in 148 Patients
`with Melanoma and Breast Cancer. Thomas J. Miner, Craig D. Shriver, Mary
`E. Maniscaico-Theberge, Robert J. Christie. Oncology Service, Walter Reed
`Army Medical Center, Washington, D.C.
`Sentinel node biopsy (SLN) can identify the first-draining lymph node in
`melanoma and breast cancer. Duetoits tattooing effects, use of a blue dye
`technique mandates removal of injected tissues and precludes SLN in
`patients who present to the Surgical Oncologist having already had their
`WLE or jumpectomy. In addition, previous authors have suggested that
`wide local excision (WLE) prior to SLN disrupts the lymphatic system,
`thereby making the procedure problematic. We perform sentinel node
`biopsy using a non-blue dye technique, injecting clear unfiltered Tc-99m
`sulfur colloid alone in the perimeter of
`the tumor or prior biopsy.
`Lymphoscintigraphy and intra-operative gamma probe are used to identify
`the sentine! node. Between December 1995 and October 1998, 148
`patients entered into IRB-approved sentinel node protocols (melanoma
`n=91, breast cancer n=57). 67/148 patients (47%) had a prior melanoma
`site excision or breast lumpectomy: the sentinel node was localized in
`65/67 (97%), no difference vs. patients with biopsy alone (p=.73, NS,
`logistic regression). Per study protocol, breast cancer patients went on to
`have full axillary dissection at the same operation after sentinel node
`removal: the breast sentinel node negative and positive predictive values
`were 98% and 100% respectively. We conclude that this non-biue dye
`technique is accurate for identifying the sentinel node, and expands the
`application of SLN to include patients regardless of prior biopsy type.
`
`*481
`
`Double-Blind, Placebo-Controlied, Multicenter Study of 6% Miltefosine Sofu-
`tion, a Topical Chemotherapy for Cutaneous Metastases from Breast Cancer. R.
`Leonard, J. Hardy, G. Van Tienhoven, S. Houston, P. Simmonds, J. Mansi,
`C. Rowland, M. David, M.B. Mac Iltmurray, J. Barret, M. Moriarty, C.
`Vernon, P. Mac Leod. Western General Hospital, Edinburgh. Royal Marsden
`Hospital, London. Academisch Medisch Centrum, Amsterdam. Saint Tho-
`mas’ Hospital, London. Royal Hants Hospital, Southampton. Saint George's
`Hospital, London. Royal Devon Hospital, Devon. Laboratoire ASTA Medica,
`Mérignac. Lancaster Royal Infirmary, Lancaster. Royal Berkshire Hospital,
`Reading. Saint Luke's Hospital, Dublin. Hammersmith Hospital, London.
`Patients and Methods: Miltefosine belongs to a new therapeutic class of
`cytostatic agents whichare related to phospholipids. Cytotoxic activity was
`demonstrated on a wide range of turnors. Thesite of activity seemsto be the
`cell membrane. In a double-blind placebo-controlled, multicenter phase lil
`study, a total of 52 patients with inoperable progressive skin lesions from
`histologically or cytologically confirmed breast cancer, not manageable by
`radiotherapy or systemic treatment, with superficial or “flat” skin lesions
`(estimated depth of invasion < 1 cm) were randomized to receive either
`6% miltefosine solution (MIL), or placebo (PLA). The solution was applied
`at the dose of 2 drops/10 cm?, once daily during the first week and twice
`daily thereafter until treatment failure. Results: Treatment groups were well
`balanced for inclusion/exciusion criteria. In term of both intention to treat
`(ITT) and per protocol (PP) analysis, time to treatment failure (TTF), the
`primary parameterof this study, showed a significant superiority of MIL
`group compared to PLA group: Median TTF in MIL group is nearly three
`times longer than in PLA group (56 days compared to 21 days: p = 0.004).
`Rate of response for MIL was 42.1% (PP analysis) and 33.3% (ITT
`analysis) against 4.2% and 3.7% respectively for PLA (p = 0.006).
`Objective cutaneousreactions (erythema, skin dryness, desquamation) and
`subjective cutaneous reactions (burning, itching, local pain) were mainly
`seen in the MIL group with frequency ratessimilar than those observed with
`MIL in phase I} studies. Conclusion: MIL is confirmed as an effective
`palliative option for cutaneous metastases from breast cancer where no
`other treatment is appropriate. Skin reactions, when present, are well
`tolerated and rarely require treatment modifications.
`
`Proceedings of ASCO Volume 18 1999
`
`*480
`
`A Large PhaseI! Trial of Paclitaxel Administered as a Weekly One HourInfusion
`in Patients with Metastatic Breast Cancer. £.A. Perez, D.H. Irwin, R. Patel,
`C.L. Vogel, J. Kirshner. Mayo Clinic Jacksonville, Jacksonville, FL. Alta
`Bates Comprehensive Cancer Center, Berkeley, CA. Comprehensive Blood
`and Cancer Center, Bakersfield, CA. Columbia Cancer Research Network,
`Aventura, FL. Hematology/Oncology Associates, Syracuse, NY.
`Small phase1/I1 clinical trials have demonstrated the activity and tolerabil-
`ity profile of weekly paclitaxel for the treatment of metastatic breast cancer
`(MBC). With the goal of confirming these preliminary data, we designed a
`prospective phase II
`trial to determine the response rate,
`toxicity, and
`tolerability in a large cohort of patients (pts) with MBC. The study includes
`200 pts [receiving 1st, 2nd or 3rd line chemotherapy, prior or no prior
`taxanes, prior or no prior high dose chemotherapywith transplant (HD/stem
`cell)] encompassing the heterogeneity of MBC. Pts received 80 mg/m? of
`paclitaxel weekly as a one hour infusion along with dexamethasone 20mg,
`an H-2 antagonist and diphenhydramine 50mg IV 30 minutesprior to each
`dose. One cycle equaled 4 weeks. Response assessments were doneevery 3
`months and the FACT-Breast and FACT-Taxane questionnaires were com-
`pleted each month. 187 pts have been enrolled; 130 pts have been
`evaluated for response to date. Pt characteristics for the first 130 are: Mean
`age 59.4, ECOG performancestatus 0/1/2:52/60/18. The mean numberof
`
`cycles given has been 4.1 (range 1-14). Subsets of patients are defined as:
`HD/Stem cell Rx
`Prior taxane Rx
`Prior metastatic Rx
`
`YES
`
`NO
`
`YES
`
`NO
`
`NONE
`
`ONE
`
`Two
`
`
`N=14 N=116 N=45 N=85 N=23 N=73 N=34
`
`8 pts developed Gr 3/4 anemia and 22 experienced Gr 3/4 myelosuppression.
`There have been no Gr 3/4 infectious episodes. 58 pts experienced Gr 1/2
`peripheral neuropathy (PN). 10 pts who had Gr 3 PN (no episodes of Gr 4 were
`documented) were removed from study after receiving a mean of 4.3 cycles; 3 of
`these had not had recommended dose reduction after Gr 2 PN. 27 pts developed
`Gr 1/2 musculoskeletal events and 2 had Gr 3/4 musculoskeletal toxicity.
`Overall, the toxicities have been well tolerated by this pt population.To date, the
`mean delivered dose is 77.5 mg/m?/week. Best response to therapy was 6 CR,
`21 PR, 46 SD, 38 PD and 19 NE.Thisis a preliminary report for this ongoing
`study whichwill finish accrual in January 1999, Detailed response, toxicity and
`quality of life data for the 200 pt cohort, and all the subset groups will be
`available by May 1999.Grant support provided by Bristol-Myers Squibb.
`*482
`
`(T): Phase Il Study in HER2
`Weekly (W) Herceptin (H) + 1 Hour Taxol
`Overexpressing (H2+) and Non-Overexpressing (H2—) Metastatic Breast
`Cancer (MBC). M Fornier, AD Seidman, FJ Esteva, M Theodoulou, M
`Moynahan, V Currie, M Moasser, N Sklarin, T Gilewski, A Surbone, C
`Denton, D Bacotti, J Willey, A Bach, V Reuter, G Hortobagyi, L Norton, C
`Hudis. Memorial Sloan-Kettering Cancer Center, NY, NY. M.D. Anderson
`Cancer Center, Houston, TX.
`Successful translation of preclinical synergy (Baselga et al. Cancer Res
`58:2825-2831, 1998) to clinical benefit (Stamon et al. Proc ASCO °98)
`has been demonstrated for T (q 3 W) + H (W). Dose-dense W LhrT is active
`and well tolerated (Seidmanet al. J Clin Oncol 16:3353-3361, 1998). We
`treated 42 pts with MBC with W lhr T + H. After dexamethasone 10 mg.,
`diphenhydramine 50 mg., and cimetidine 300 mg, T 90 mg/m?is given
`over lhr., foliowed by H 2 mg/kg. over 30 min., all i.v. (H loading dose 4
`mg/kg over 90 min., week 1). Median (M) age: 50 yrs (33-67), M Karnofsky
`Performance Status 90% (70-100), M organ systems with MBC: 3 (1-5);
`86% of pts had visceral dominant disease. Pts had 0 (7%), 1 (71%), 2
`(17%), or 3 (5%) prior regimens: 17% prior (>1 yr) taxane, 79% prior
`anthracycline (A); 21% were A-refractory. 607 infusions have been given,
`M 16/pt (1-25). M delivered dose intensity to date is 82 mg/m2/wk
`(57-90). Peripheral neuropathy is the major dose-limiting toxicity (grade
`2:35%, grade 3:8%); grade 34 neutropenia: 10% of pts, with 2 episodes of
`febrile neutropenia (0.3% of infusions). Other grade 34 toxicity: Diarrhea
`(7%), onycholysis with infection (7%). Serial ventriculography shows no
`significant decline in LVEF at week 8 (n = 35) or 16 (n = 25). One cardiac
`event: A pt completing a cumulative A dose of 615 mg/m? 4 weeksprior to T
`+ H had transient CHF. 23/36 evaluable pts have responded (64%; 95% Cl
`42-76%), 3 with CR (skin + nodes, lung, liver). Responses among H2+
`pts: 20/28 (71%; 95% Cl 52-81%), H2— pts: 3/8 (37.5%; 95% Cl
`14-66%). WT + H is active and safe in MBC. Accrual continues to better
`characterize efficacy, particularly for H2— pts. H is integrated into CALGB
`9840, comparing W T(1h) + H to q 3W T(3h) + H. Support: Genentech.
`
`2
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`

`

`*480
`
`A Large PhaseIl Trial of Paclitaxel Administered as a Weekly One Hour Infusion
`in Patients with Metastatic Breast Cancer. £.A. Perez, D.H. Irwin, R. Patei,
`C.L. Vogel, J. Kirshner. Mayo Clinic Jacksonville, Jacksonville, FL. Alta
`Bates Comprehensive Cancer Center, Berkeley, CA. Comprehensive Blood
`and Cancer Center, Bakersfield, CA. Columbia Cancer Research Network,
`Aventura, FL. Hematology/Oncology Associates, Syracuse, NY.
`Small phase I/II clinical trials have demonstrated the activity and tolerabil-
`ity profile of weekly paclitaxel for the treatment of metastatic breast cancer
`(MBC). With the goal of confirming these preliminary data, we designed a
`prospective phase I! trial to determine the response rate,
`toxicity, and
`tolerability in a large cohort of patients (pts) with MBC. The study includes
`200 pts [receiving Ist, 2nd or 3rd line chemotherapy, prior or no prior
`taxanes, prior or no prior high dose chemotherapy with transplant (HD/stem
`cell)] encompassing the heterogeneity of MBC. Pts received 80 mg/m? of
`paclitaxel weekly as a one hour infusion along with dexamethasone 20mg,
`an H-2 antagonist and diphenhydramine 50mg lV 30 minutes prior to each
`dose. One cycle equaled 4 weeks. Response assessments were done every 3
`months and the FACT-Breast and FACT-Taxane questionnaires were com-
`pleted each month. 187 pts have been enrolled; 130 pts have been
`evaluated for response to date. Pt characteristics for the first 130 are: Mean
`age 59.4, ECOG performance status 0/1/2:52/60/18. The mean numberof
`cycles given has been 4.1 (range 1-14). Subsets of patients are defined as:
`
`HD/Stem cell Rx
`
`Prior taxane Rx
`
`Prior metastatic Rx
`
`YES
`
`NO
`
`YES
`
`NO
`
`NONE
`
`ONE
`
`TWO
`
`N=14 N=116 N=45 N=85 N=23 N=73 N= 34
`
`8 pts developed Gr 3/4 anemia and 22 experienced Gr 3/4 myelosuppression.
`There have been no Gr 3/4 infectious episodes. 58 pts experienced Gr 1/2
`peripheral neuropathy (PN). 10 pts who had Gr 3 PN (no episodes of Gr 4 were
`documented) were removed from study after receiving a mean of 4.3 cycles; 3 of
`these had not had recommended dose reduction after Gr 2 PN. 27 pts developed
`Gr 1/2 musculoskeletal events and 2 had Gr 3/4 musculoskeletal
`toxicity.
`Overall, the toxicities have been well tolerated by this pt population. To date, the
`mean delivered dose is 77.5 mg/m*Aweek. Best response to therapy was 6 CR,
`21 PR, 46 SD, 38 PD and 19 NE.Thisis a preliminary report for this ongoing
`study whichwill finish accrual in January 1999, Detailed response, toxicity and
`quality of life data for the 200 pt cohort, and all the subset groups will be
`available by May 1999. Grant support provided by Bristol-Myers Squibb.
`
`3
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