Thirty-Fifth
`Annual Meeting of the
`American Society of Clinical Oncology
`May 15-18, 1999
`Atlanta, Georgia
`Program/Proceedings
`
`
`
`Copyright 1999 American Society of Clinical Oncology
`
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`Hospira v. Genentech
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`Genentech Exhibit 2049
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`Proceedings of ASCO Volume 18 1999
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`BREAST CANCER
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`135a
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`515
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`516
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`A Promising Second Line Treatment with Weekly Taxol (T) in Anthracycline
`Recurrent, Advanced Breast Cancer (ABC) Patients (PTS). Mickiewicz E.,
`Alvarez A.M., Brosio C., Giglio R., Cinat G., Rodger J., Nicolas, C. instituto
`de Oncologia Angel H. Roffo, Universidad de Buenos Aires, Argentina.
`The expected responserate with taxanes as second line treatment has been
`reported to be around 22-42%. We have previously shown our experience
`with weekly T (ASCO 96, ASCO 98, EORTC-UICC 98), and taking into
`account the good response rates obtained, we decided to apply this
`schedule in heavily pretreated pts with ABC. Objective: Evaluation of
`response, response duration andtoxicity, in ABC pts receiving WT. Material
`and methods: Between July 95' and July 98’, 49 pts with ABC andat least
`one previous treatment with anthracyclines, were included. Median age: 47
`years (range: 32-74). Thirty six of the 49 pts had received prior treatment
`with T. Previous lines: 1: 15 pts (30.65%), 2: 21 pts (42.9%), 3: 12 pts
`(24.5%), and 4: 1 pt (2%). Disease extension included: 1 site only: 26 pts,
`2 sites: 19 pts and 3 sites: 4 pts. Fourteen pts had visceral metastases (4
`hepatic metastases). Treatment schedule: 39 pts received Taxol 100
`mg/m?/w for 24 weeks and 10 pts Taxol 80 mg/m?/w for 3 weeksof a 4 wk
`cycle for a total of 8 cycles. All of them were premedicated with: ranitidine
`150 mg + diphenhydramine 50 mg, without dexamethasone.
`Results: CR: 8 pts. (16.32%), PR: 22 pts. (44.89%), overall responses: 30
`pts (61.21%), stable disease: 15 pts. (30.61%), progression: 4 pts.
`(8.16%). Response duration for CR was: 17, 10,7, 9+, 6,6, 4+, and 2+
`months, while duration for PR varied from 2+ to 9+ months.
`
`Toxicity: With a total of 656 weeks only 1 pt had leukopenia G3, 2 pts. with
`paresthesia G3, subungual mycosis in 6 pts. There was neither delay nor
`suspension of treatment due to toxicity. Conclusions: 1) The overall
`response was 61.21%, with mild and moderate toxicity. 2) Both treatment
`schedules of WT seem to be promising as second line therapy for ABC, but
`pts were glad to have a week ofrest.
`
`Primary Chemotherapy in Operable or Locally Advanced Breast Cancer (OLABC)
`Using a Regimen Containing Vinorelbine (V), Cisplatin (P) and Continuous
`Infusion of Fluorouracil (FUci).
`/da Minchella, Marco Colleoni, Franco Nole,
`Manuela Sarti, Chiara Catania, Bettina Ullrich, Carlo Greco, Giulia Peruz-
`zotti, Maria Giulia Zampino, Emanuela Marrocco, Aron Goldhirsch. Dept. of
`Medicine and Radiation Oncology, European Institute of Oncology, Milan,
`Italy.
`Protracted FUci has been shown to be extremely effective together with
`epidoxorubicin and P (Smith et al, JCO, 95). Based on previously observed
`results in metastatic disease (VIFuP Regimen-Noléet al, ASCO 98), we
`evaluated efficacy and tolerance of the combination in patients (pts) with
`OLABC. Thirty-five pts with invasive carcinoma and a median age of 47
`years (range 31-70) were treated with FUci (200 mg/m?) P (60 mg/ m? i.v.
`on day 1) and V (20 mg/ dose i.v. on day 1 and 3) for three 21-day cycles.
`Partial or complete remitters (PR/CR)} received 3 more courses before
`surgery. Twenty-seven pts had 72 disease, 3 pts-T3 and 5-T4d. Clinical
`axillary-node status was NO in 15 pts, N1 in 15 and N2 in 5 pts. This
`preliminary analysis includes data on 23 pts assessable for response (12
`too early). Results: We observed cPR in 18 pts (72%), cCR in 2 pts (8%),
`cSD in 2 pts (8%), with an overall response rate (RR) of 80%. Complete
`pathologic response (pCR) was observedin 1 out of 23 pts (4%). Subjective
`tolerance was excellent. Side effects in 114 administered cycles included:
`grade 1-2 nausea (55% of cycles), grade 1 constipation (16%), grade 1
`mucositis (14%) grade 1 hand-foot syndrome (21%), grade 1 asthenia
`(18%). Grade 3 hand-foot syndrome, nausea and diarrhea were registered
`only in 1% of cycles. No grade 4 hematological toxicity was observed.
`Preliminary results show a significant efficacy of the ViFuP regimen. RR
`wasidentical in operable and locally advanced breast cancer. The combina-
`tion was subjectively well tolerated and the jack of significant alopecia has
`been appreciated by the pts. This regimen is a reasonable primary
`treatment option for OLABC.
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`517
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`518
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`Prevention of Breast Cancer Relapse by Neoadjuvant Chemotherapy: Studies on
`the Mechanisms. Satya M. Murthy, Stephen E. Reid, Edward F. Scanion,
`Janardan D. Khandekar. Surgery and Medicine Evanston, Northwestern
`Healthcare, Evanston, Illinois.
`An important cause for cancer recurrence is reseeding of cells released
`during surgery. Neoadjuvant chemotherapyinterferes with this process and
`reduces recurrence. These postulates are tested in a mouse model using
`the mammary tumor line, TA3Ha. Peripheral blood collected from TA3Ha
`tumorbearing mice wasinjected i.p. into naive mice. 7/8 mice developed
`lethal ascites tumor. Blood collected from comparable mice treated 4 days
`previously with doxorubicin failed to induce tumor developmentin 4 naive
`mice, suggesting that doxorubicin interfered with the reseeding ofcells. In
`a clinically relevant model, TA3Ha tumors grown orthotopicaily were
`treated with doxorubicin 4 days before or 4 days after surgical removal of
`the tumor. Cure rates in these groups were 70% and 38%, respectively (J
`Surg Oncol 61:273, 1996). Similar results were obtained in our liver
`wound modet (Cancer 64: 2035, 1989). Mice subjected to liver wedge
`resection and werei.v. injected with TASHa cells immediately after surgery.
`Groups of mice were treated with doxorubicin one day before or 5 days after
`surgery and tumorinjection: Tumor at the woundsites in these mice were
`0% (0/10), and 50% (5/10), respectively. These results suggest that
`doxorubicin may aiso modulate the host environmentto prevent tumorcell
`migration. A biodistribution study on the i.v. injected 14C-BrdU labeled
`TA3Ha cells showed that doxorubicin (given one day earlier) reduced the
`numberof cells reaching the liver woundsites. Cell numbers (radioactivity
`nCi/g mean+s.d) in the test and the control mice were 0.4+0.2 and
`0.9+0.2, respectively. Furthermore, doxorubicin reduced the production/
`secretion of chemotactic proinflammatory cytokines (pg) at the wound
`sites. IFN-g 24+0.4 vs. 71+0.2, TGF-b 0+0 vs. 3.3+1.2, and TNF-a
`39+ 3 vs. 51+ 5. Supported by Julia Michel’s Fund, Carol Gollob
`Foundation, and Marvin and Lori Gollob.
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`Cisplatinum and Vinorelbine (CV) in Metastatic Breast Cancer (MBC) After
`Anthracycline Failure. G/orgio Mustacchi, Rita Ceccherini, Michela Muggia,
`Silvia Milani, Vito Amoroso, Vinicio Fosser. Divisione Oncologia medica,
`Ospedale Civile, Vicenza,Italy.
`CV is an effective combination in MBC (Mustacchi, San Antonio Meet-
`ing1991; Audhuy, ASCO 1998).
`In the present study 23 MBC patients (mean age 55 yrs, range 33-75), who
`relapsed after anthracycline chemotherapy, were treated with CV (C: 100
`mgs/sqm d 1, V: 25 mgs/sqm dd 1& 8; q 3 weeks) for a maximum of 6
`cycles. Previous anthracycline treatment was adjuvant in 8/23 pts,first line
`for metastatic disease in 12/23 and both in 3/23. Metastatic sites were
`bone (2/23), soft tissue (4/23), visceral (10/23) and multiple (7/23).
`Antiemetics for acute and delayed emesis and prophylactic G-CSF (5
`megs/kg dd 13-15) were used. Toxicity was mild: 5 G3 (4 emesis,
`1
`asthenia); 6 patients needed blood transfusions (13 units); none suffered
`alopecia; 51/110 cycles in 20/23 patients were delayed for ANC<1000 at
`day 20. The Overall RR was 65.2% (17.4% CR, all visceral). Median TTP
`was 7.5 months and median Overall Survival was 14 months (8-56).
`According to previous anthracycline chemotherapy response, RR was 59%
`in ‘resistant patients and 68.7% in ‘non resistant’. At 12 months 55.2% of
`patients werestill alive and at 24 months 31.1%.
`In conclusion, CV seemsto be a highly effective second line treatmentfor
`MBC, anthracycline cross not resistant.
`it
`is easy to menage on an
`outpatient basis. The absenceof alopecia is very importantfor the patients.
`Our results confirm previous reports and are consistent with data recently
`reported in the same setting with several multidrug combinations including
`taxanes. The CV schedule is not expensive and well tolerated. A short
`treatment with prophylactic G-CSF does not avoid delays but reduces
`hematologic toxicity at nadir.
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