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`ISSN 1359-6345?
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`EJC Supplements
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`The European Cancer Conference
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`1359-6349(200510)3 :z;1-
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`NOVARTIS EXHIBIT 2099
`Par v. Novartis, IPR 2016-01479
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`NOVARTIS EXHIBIT 2099
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`204
`
`oregression and toxicity Pts were randomized tr; GEM K100 rug/m2 ,v d 1 +8
`and CAP 650 rug/m2 po (1 12 hrs d 1.14 every 3 w or GEM 1000 rug/mZ
`weekty x7.
`1 w rest and then weekiy x3 qéw. Tit continued for 6 mo or
`until progression, The study was designed to detect a“: increase of median
`survival from 5 to 7 months. CB was evaiuated based or changes in
`pain/pain medication, KPS and weight during a period >4 weeks. The trial
`was independently monitored.
`Results: From 7/01 to 6/04 319 pts from 30 institutions in 8 countries were
`randomized, 79% had metast. disease, 67% required pain medication and
`53% had KPS of 290, The median OS was 8.4 ms for GEMCAP and 7 3 mo
`for GEM (p=0,314)t 89% of all patients have died, Confirmed response
`rates were 10 1% vs, 7 9%, median duration of resoonse 7 4 vs, 5.9 mo
`and median TTP 4.8 vs. 40 mo for GEMCAP and GEM resp, A multivariate
`Cox regression of OS on strat. factors and in revealed that in pts with KPS
`290 those treated with GEMCAP had a significantly higher median 08
`of 101 vs 75 m0 (p:O 033), 111 pl: (73%) with GEMCAP and 121 pts
`(82%) with GEM were at least 4 weeks on study trt and evaluable for C8.
`Conctusions: An update on CBR and other 00L parameters in relation to
`clinical outcome wltl be presented;
`Supported in part by Hofimanntal‘tocne and Eii Liliy Switzerland
`
`ORAL
`718
`Results of a phase II study with sunitinib malate (81.111248) in
`patients (pts) with advanced neuroendocrine tumours (NETs)
`M, Krglltet, H. Lenzz, N, Meropois. J Posev". J, Pious? D Ryana.
`E. Bergstandfi it, Stuarts, C, Baum? C, Fuchs‘, ’Dana-Ferber Cancer
`Institute, Boston, USA,“ QUSC/Norrls Comprehensive Cancer Center,
`Los Ange/es, USA; 7Fox Chase Cancer Center, Philadelphia, USA,
`‘Unr‘versr‘ty of Alabama. Birmingham, USA; 5Wasnlngion University.
`St Louis, USA; Efv'assactrusetts General Hospital, Boston USA;
`7 UCSF Comprehensive Cancer Center Sap Francisco, USA; 589th Israel
`Deaconess Meatloaf Center, Boston. USA: SPfizer (no, La Jolie, USA
`
`Background: NETS are characterised by an indolent course and are
`often resrstant to standard cytotoxic chemotherapy. These tumours are
`highty vascular with both carcinoid tumours and pancreatic (zsiet
`cell";
`NETS expressing high ieveis of VEGF and VEGFR‘ Sunitinib maiate rs an
`oral mulfitargeted tyrosine kinase inhibitor that spocrfically inhibits VEGFR,
`PDGFR, KlT, RE? and FLTS. and has shown activity sn pts wrtn NETS
`included in mass 1 trials
`Patients and methods: Pts in": 109) with advanced unreseotabie NETS
`(42‘s carcimid, {:6 rate: 391%} received summit) 50 mg/day (so for 4 weeks
`foliowed by 2 weeks off treatment. Cycles were repeated every 6 weeks
`Prior ohemotnerapy was allowed and p15 VGCE/‘utét‘g ootreotide could
`continue with treatment on study in addition to response. survive: and
`adverse events. quality at his was measured (E343?) and FACtT-Fatsgtre
`substrate) and correi'ative safety/efficacy anatygas were undertaken Using
`both stmitinin plasma taveis and NET biomarkers,
`'ange
`Results: Data are availahte for 302 pts {met an no. of cycles: 5,
`1 ~14; median dose intensity 93%) with the following characteristics: median,
`age: 57 yrs (range 32- 81}, MW {‘79) 59/41. ECOG PS 0/1 (‘75) 54/43. The
`most common {>299} grade 3/4 treatmentrelated adverse events iAEs)
`9/9} inctuded latégue 125/01, neutrooenta 112M},
`thrombocytnponia (810},
`hypertensron (8K)}, vomiting {ES/{1). nausea (8U), diarrhoea {510), dehydration
`(At/UL mucosa! inflammation (3/0), anorexra (3/0) and glossodvnia (3/0;
`Déscontinvatrons dye to ASS were reported for 7% of pts
`Best obiective turrour response rates defined by RESlST were (n =1027;
`partiai response (PR1 9 pts {9%}; stable disease (80) 8:1 {82%) and
`
`progressive disease (PD; 41 {3%) Best response according to tumo
`
`is shown, Median time to :umour response was 16 weeks and me:
`to tumour progression was 4’3 weeks loarcr’noid = $2 weeks; islet set! :»
`33 weeks; Results from analyses investigating Cone lion between NET
`biomaz'xers and treatmenweiated i')i.ilcomes are pending
`
`Sf}
`
`9E}
`DR"
`
`
`
`we}
`«7%;
`or;
`45:
`amt/3‘ 5%Cl58‘24?
`lsletwll‘tncmi
`
`
`
`
`245%:
`381mm 010%;
`112%i95%Ctli—"2,9
`{Taminukl‘inéltfi
`
`‘ Patients with baseiine and a: teas! 1 subsequent imaging ass
`SW ,6: ”Confirmed
`resoonse by rnvesl‘rgator {at least two assessments}
`Conclusions: Sumtinilii shows singie-agant clinical amivity in pts with
`advanced unresectable NETS and 15 associated with acceptable adverse
`events that resuit rareiy in treatmer‘t discontinuation,
`
`Prnffcrcd Pa port;
`
`ORAL
`719
`Randomized, multlcenter, phase 3 study of tst-Iine irinotecan +
`SFU/folinic acid vs cisplafin 1» 5FU in patients with advanced gastric
`cancer » quality of life analysis
`CLEgzzio“, Jr ZG‘USklZ, M. Banks, C. Barone‘, v. Vaivere‘, C Pesohetf’,
`M. Wenozt‘s, E. Goker7, R. Bugate, ’Urrlverslta Carlo/ice del Sacro
`Cuore, Medical Oncology, Rome, Ila/y; 2Semrnelweis University,
`Budapest, Hungary; 3 Vl/ielkopo/skle Can/rum Orrkologii, Poznan Poland;
`‘North Estonian Regional Hospital Cancer Center, Tallinn, Estonia;
`5Klinlkum Radars o’er {San Munich, Germany; sl‘vlarl‘rosovsky Hospital,
`Szombathely, Hungary; 7599 Unintrerslly Hospital, Izmir. Turkey host/tut
`Claudius Regaud, Toulouse, France
`
`Background: An open—label. multicenter study of 1s:.line advanced gastric
`cancer 915 was desrgned to compare the effects of GP?“ + SFU/FA
`wrth CDDP + SFU‘ anary efficacy variable: time to progressmn (TTP);
`secondary endpoints time to treatment torture (TTF). Overalt SLWWal {03}.
`global health status/00L seats, and saletyr
`Methods: Male and lemaie {:13 aged 285/? v were randomized to receive
`CPT-H 80 mg/m2 iv as 30~min infusion, then FA 500 mglm2 iv over Zn,
`and then SFU 2000 mg/mz iv over 22 h weekly {or 6 wk (5) 0r CDDP
`11$)Grng/m2 iv as 1—3 n infusion on day 15 and tnen SFU 1000 mg/mZ/d
`continuous infusion over 5 d every 4 wk (CF) Treatment was administered
`up to srogression. unacceptabie toxroity, or consent withdrawa,
`Results: Of 337 randomized pts, 333 {17C} in 113' 163 in CF} were treated,
`M the full~analysis population, a trend toward superiority was noted for
`TTP with IF vs CF (HR 1.23; 95% Cl 0.97““. .57, P = 0,088) corresponding
`to a 19% progression in rsk reduction Median TTP for lF vs CF; 5,0 vs
`4.2 mo: median TTF: 4.0 (3 64¢ 81 vs 34 (2545,57: mo {HR 143; 95%1’3
`1144,78; P = 0.018). There was no difference in 08 Although there were
`no significant differences between summary measures of postbasetrne
`global neatih status/00L, there was a trend toward significance for the
`maxrmum and mean measures fa‘mring 1F Mean summary measures for
`several seconcarv QOi endpoints stowed Significantly better results for
`1F vs CF egy physical tunctionmg (F‘ <0005)‘ nausea/vomiting (P <0.05},
`and Euroqol S'Dimenslon thermometer (P <0 005} and neatth utitity index
`(P<0.05), 67 pts (40%) in 1F had grade 3/4 drugrelated AEs vs 73 (44%}
`in CF.
`iF Qts had more grade 3/4 drugsrelated diarrhea (21 8% vs- 7 2%;
`C? pls had more grade 3/4 neutropenia (52% vs 25%}. febrile neutropenra
`or neutropenic inteetron (102% vs 43%), stomatitis (16.9% vs 2.4%), and
`nausea (98% vs 4.8%, CF me had more nematotogir: and renal toxscitles
`More ms Withdraw from the study due to drug‘i’etatec AEs With C, man
`With IF (215% vs 100% P zoned}, includmg 5 toxic deaths with CF vs 1
`with ll?
`Conciusions: in advanced gastric cancer pts EF snowed a trend towards
`TTP SUDElloi’lty vs CF, lF demonstrated significant
`rovement in severat
`
`QDL scales vs CF, as well as a better safety protiie T as CPTA‘; + Sim/FA
`is a safe atternativs test—tine treatment option without C0313 for advanced
`
`gastric, ca .er and may he rrsafu in treating p15 wit? mar sartormarsce
`status
`
`ORAL
`720
`An intensive weekly chemotherapeutic regimen with Sfluorouracii,
`ieucovorln, cisplatin and epidoxorubicin {PELFW} as adjuvant
`treatment in highwisk radically resented gastric cancer patients:
`results of a randomised controlled trial
`
`1‘ @85ch R, Lab/lance? C, Barons? C Gama“ 1*”, E Artii’ilg
`;
`omimm / {istaianog Ct Banana?“ 8 83rn»7_ 5 Hanan“ timer/cm
`
`Dweller/era (Ewe/tall Rinmti-Umversl/a' Ff (Illrzica Dr Oncologia Med/ca
`Ancorra, Italy, 2fizlenaa Ospeda/fera Ospedal/ Rim/ll Bergen/o, Once/ogre;
`Medics, Bergamo Italy; :‘Umversrta‘ Cattel/ca-Polrclmlce Gamer/r,
`Olmntdgla Medical, Roma, Mary: “st/rum Human/tag (Lingo/9913 Medics
`xii/am,
`lie/y; 5Az/enda Ospedaiiera Santa Croce, Once/ogre Med/ca
`Pesaro, Italy: GOssi’X/ar’e Mal/net’s, Oncologra Med/ca,
`lorma ire/v
`7Ospedale TFBVngiO, Oncology/a Med/ca, Ties/19m) Italy, fi/Sfihih‘) Mar/r)
`Neg/1‘, Milena lie/yr JOspedale Poms. Once/ogre Med/ca, Mentor/d,
`lie/y; ’H’Gspeda/e San Gerardo, Oncology/a Med/ca, Monza.
`ire/y
`
`in rrietastattc and looalty advanced
`l”EL/Cw showed Significant benefit
`gastric Cancer {J Clin Oncoi 19537 Br J cancer 25104) This trial was
`designed to determine whether
`this effect
`transfates into a survival
`anvantage in hignrrisk radically rescaled gastric :anser patients
`From January 1998 to January 2003,
`£160 patents with Stage M3
`N0 and $23 N123, were rardomised to receive PELFw, 8 weerly
`acménistration of CtSplalirl as mtg/m}, leJcovorzn 250 reg/r717, epidoxounicm
`35 mgr/mg. Stiuorouracrl 500 mom“? glutathione 1500 r‘rrglrn2
`ienograstin
`was administered daiiy for 6 days every To:
`the dose oi Eng/Kg, or
`
`
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`NOVARTIS EXHIBIT 2099
`Par v. Novartis, IPR 2016-01479
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`NOVARTIS EXHIBIT 2099
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