Download - Le traitement néo-adjuvant du cancer du pancréas borderline ou localement avancé par Eric Raymond
Letraitementnéo-adjuvantducancerdupancréasborderlineou
localementavancé
Prof.EricRAYMONDChefdeserviced’oncologiemédicale
HôpitalSaint-JosephParis14ème
SOIREEDIGESTIVEdeSAINTJOSEPHMardi23mai2017à20h
Salle de conférenceBâtiment Notre Dame de Bon secours
Porte 10 - Niveau -1
Lecancerdupancréas
Le cancer du pancréas (adénocarcinome) est au 10ème rang des cancers les plus fréquents et garde un mauvais pronostic le plaçant au 5ème rang des causes de décès par cancer
L’incidence du cancer du pancréas est en forte augmentation. Chez l’homme, le taux d’incidence annuel standardisé (100 000 homme-années) est passé de 4,9 cas à 9,5 cas entre 1980 et 2015 et chez la femme de 2,0 cas à 6,3 cas sur la même période
Il s’agit d’un cancer agressif souvent d’emblée métastatique et provoquant rapidement une jaunisse, des douleurs et une altération importante de l’état général avec fatigue, amaigrissement et perte d’appétit. Il s’accompagne fréquemment de complications thromboemboliques, inflammatoires, métaboliques et immunologiques jouant un rôle important dans l’évolution des malades
Lecancerdupancréasestleseulcancerdontlamortalitéaugmentedanslesdeuxsexes
Tauxdemortalitédescancerdupancréascomparésauxautrescancers12
Lecancerdupancréasestactuellementla4èmecausedemortalitéparcancerenEurope12
Homme Femme60
40
30
20
10
0
50
1970 1980 1990 2000 2010 2020 1970 1980 1990 2000 2010 2020
20
15
10
5
0
Décèsp
our1
00,000pop
ulation
Poumon
Colorectal
Prostate
Leucémie
Pancréas
Estomac
Poumon
Sein
Colorectal
Estomac
Utérus
Leucémie
Pancréas
12..Malvezzi 2014.Annals ofOncology.European cancermortality predictions fortheyear 201425.Pancreatic Canceractionnetwork.2012.Thealarming rise ofpancreatic cancerdeaths intheUnitedStates:Why we need tostemthetide today
Lecancerdupancréasseraresponsabledeplusdedécèsquelecancerduseinen2020
MortalitéparcancerdupancréasauxUSAcomparéeauxautrescancers25
2010 2020 2030
20
15
10
5
0
poumon
Pancréas
SeinColorectalProstate
25.Pancreatic Canceractionnetwork.2012.Thealarming rise ofpancreatic cancerdeaths intheUnitedStates:Why we need tostemthetide today
Estim
ationde
scancersparm
illiers
Lestauxdesurvieducancerdupancréasn’ontpaschangéconsidérablementdepuis40ans
SurvieparcancerdupancréasenAngleterre13
Alorsquelasurviedelaplupartdescancerss’estamélioré,celleducancerdupancréasrestetrèsbassedepuis40ans13
1971-1975 1976-1980 1981-1985 1986-1990 1991-1995 1996-2000 2001-2003 2003-2007 2004-2008 2005-2009
90
80
70
60
50
40
30
20
10
0
Survie(%
)
52
21
2
2731
12
85Sein
44Leucémie
3Pancréas
58Vessie
82Prostate
43Ovaire
13.CancerResearch UK.Cancersurvival statistics.http://www.cancerresearchuk.org/cancer-info/cancerstats/types
Lecancerdupancréasesttardivementprisenchargeetd’autantplusdifficileàtraiter
14.Oberstein 2013.Therapeutic advances ingastroenterology.Pancreatic cancer:why is it so hardtotreat
Lessymptômessontpeuspécifiquesetretardentsouventlediagnostic
Iln’existepasdebiomarqueur,degèneoudenouvelletechniqued’imageriediagnostique
Latumeurestsouventmalsituéeauconfluentdenombreusesstructuresanatomiques
Lesmétastasessontprécocesmaisdifficilesàidentifier
L’évolutionestrapideetlediagnostiquesouventfaitàunstadeavancé
Lesaltérationsgéniquessontsévèresetfréquentes
Lachirurgiecurative nepeutconcernerqu’unnombrelimitédepatients
Lesrésistancesspontanéesouacquisesauxchimiothérapiesetàla radiothérapiesontfréquentes
Diagnostictardif/pasdedépistage
Difficultésdetraitement
Histoiredelamaladie:Unemaladieprécocementmétastatique• Lesadénocarcinomesdupancréassontcaractérisésparunelargepropensionàdévelopperdesmétastases(ganglionnaires,hépatiques,péritonéales,etc…)trèsprécocement (souventdèslediagnostic)
• Laplupartdespatientsseprésententdoncavecunemaladielocalementavancéeouunemaladiedéjàmétastatique
• R1dans17-42%descas• Chezlespatientsayanteuunerésectioncurativeletauxderechuteslocalesestde75-85%etderechutesmétastatiquesde80%
• Lestumeursapparemmentlocaliséesdéveloppentdesmétastasesdansundélaisde6-12mois(16%avantlafindelachimiothérapieadjuvante)suggérantlaprésencedèslediagnosticd’unemaladiemétastatiqueocculte
Métastatique Survie 8-12 mois
Localement avancé Survie 12-15 mois
Localisé opérable Survie 15-20 mois
60%
30%
10%
Degréd’extensionetpronosticdescancersdupancréasaudiagnostic
(dont10%‘bordeline’)
Priseenchargedesadénocarcinomesdupancréasnonmétastatiquesaudiagnostic
Chirurgiecarcinologique
semblantpossible
Chirurgiecarcinologiqued’embléedifficile
Chirurgiepremière
Yat’iluneplacepourlestraitementsnéo-adjuvants?
Traitementsnéo-adjuvants
Commentaméliorerlecontrollocaletmétastatique?
Adénocarcinomedupancréaslocalisé
Chimiothérapie adjuvante
Chirurgiesiaméliorationducontrollocaleetabsencedeprogression
métastatique
Opérable
‘Borderline’
Classificationdesadénocarcinomesdupancréasenfonctiondeleurextension
Journal of Cancer Therapy, 2016, 7, 24-40
Opérabled’embléCancerdupancréas
Patientopérabled’emblé
Artériel Portal
Tumeur Tumeur
SMVSMA
SMVSMA
Scanner
Journal of Cancer Therapy, 2016, 7, 24-40
Prévalencedeladénutritionparcancer(2005)
Hébuterne etal.Nutr 2006
Opérableradiologiquement,maisphysiquement?
• Grandâge• Anorexie• Pertedepoids• Hypo-albuminémie• Amyotrophie• Anémieinflammatoire• Douleurs• Ictère• Occlusionhaute• Altérationdel’étatgénéral• Syndromedépressif• ThrombosesveineusesetEP• Diabète• Comorbiditésdutabac
Nécessiteuneremiseenconditionphysique
préalableàlachirurgie
Pré-habilitationsystématiquepour
limiterlesrisquesperetpost-opératoires
SMARTH-HAB
Traitementsadjuvantsdel’adénocarcinomedupancréasréséqué
Journal of Cancer Therapy, 2016, 7, 24-40
RecommandationsNCCN2016
Peut-onaméliorercesrésultatsparlaréalisationd’untraitementnéo-adjuvant?
Journal of Cancer Therapy, 2016, 7, 24-40
BorderlineCancerdupancréas
D2
PAMS
VMS
Adénocarcinomelocalementavancé=pasmétastatiquemaisavecdesréserveschirurgicales
RecommandationsNCCN:cancerdupancréasborderline
Radiothérapie
Radio-chimiothérapie
Chimiothérapie
Obtenirunediminutiondevolumedelatumeurprimitive
Vérifierl’absencedemétastasesàdistance
BUTS MOYENS
Cancerdupancréasborderline
Eviterlestoxicitéspouvantretarderlachirurgie
Chimiothérapiesdescancersdupancréas
• Monothérapie:Gemcitabine
• Doublet:Nab-paclitaxel +gemcitabine
• Triplet:FOLFIRINOX
Phase III Gemcitabine Monotherapy in Advanced Pancreatic Cancer: Study Design
• Primary endpoint: improvement in specific disease-related signs and symptoms (clinical benefit), including pain and KPS
• Secondary endpoint: weight change• Other endpoints: ORR, survival, time to progressive disease
24Burris III HA, et al. J Clin Oncol. 1997;15:2403-2413.
5-FU, 5-fluorouracil; IV, intravenous; KPS, Karnofsky performance status; ORR, overall response rate; qw, weekly; qw ¾, first 3 of 4 weeks; qw 7/8, first 7 of 8 weeks.
25
Gem, gemcitabine, 5-FU, 5-fluorouracil; OS, overall survival.
Phase III Gemcitabine Monotherapy in Advanced Pancreatic Cancer: Overall Survival
Reprinted with permission. © (1997) American Society of Clinical Oncology. All rights reserved. Burris III, HA et al: J Clin Oncol, Vol. 15(6), 1997: 2403-2413.
Burris III HA, et al. J Clin Oncol. 1997;15:2403-2413.
Intent-to-Treat Gem(n = 63)
5-FU(n = 63)
P Value
Clinical benefit, %Time to clinical benefit, median, weeksDuration of clinical benefit, mean,
weeks
23.87
18
4.83
13
0.0022
OS, median, monthsOS rate, %6 months9 months12 months
5.65
462418
4.41
3162
0.0025
PFS rate, %6 months9 months12 months
2299
555
Time to progression, median, months 2.33 0.92 0.0002ORR, %
PRSD
n = 565.439
n = 57019
NS
5-FU, 5-fluorouracil; Gem, gemcitabine; NS, not significant; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, progressive disease; SD, stable disease.
26Burris III HA, et al. J Clin Oncol. 1997;15:2403-2413.
Phase III Gemcitabine Monotherapy in Advanced Pancreatic Cancer: Efficacy Outcomes
Chauffert B, Ann Oncol 2008
Gem
Gem
CRT
CRT
Chemotherapyorchemo-radiotherapy(C-RT)
Huguet F, J Clin Oncol 2007
FrontlineC-RT Chemotherapy then C-RT
Chemo then CRT
Chemo alone
Chemo then CRT
Chemo alone
PACLocally
advanced,M0
N=449 Gem2months
RCT
R2
Gemcitabine+Erlotinib
Gemcitabine
R1
Erlotinib :100mgavecgemzar ;150mgenmono.Maintenujusqu’àprogressionRCT:RT54Gy (6semaines)+Capecitabine 1600mg/m2
Patientswho notprogressed at 4months
F.Huguetetal.,ASCO2014,A4001
N=269
LAP07:ImpactofC-RTonlocalcontrol?
l Nooverall benefits ofRCT(Hammel ASCO2013LBA4003)
à Overall survival (15,2vs 16,4mois,p=0,82)à Profression-freesurvival (12,5vs 11,8:p=0,21)
l Acceptablesafety ofRCT(more nausea grade3-4:5,9%vs0)
Prob
ability
ofLP
FS
100
0 6
50 HR(95%CI):0,78(0,61-1,01)
Log-rank:p=0,055
Timefrom thefirstrandomization (month)
136133
Nbat risk patients
0
Localprogression-freesurvival
3 9 12 15 18 21 24 27 30 33 36 39 42
136133
113117
6176
3545
2130
1221
711
38
17
14
14
14
14
14
CTRCT
N Events LPFS(mois)
CT 136 125 8,4RCT 133 122 9,9
F.Huguetetal.,ASCO2014,A4001
LAP07:ImpactofC-RTonlocalcontrol?
Sitesofaprogression
l Patientsat2nd randomizationl Progression:236/269pts (88%)
à Localprogressiononly:93(39%)à Metastaticprogression(± local):122(52%)à Progressionatunknownsite:21(9%)
F.Huguetetal.,ASCO2014,A4001
Chemo(n=125)
Local Metastatic Unknown
RCT(n=111)
46% 44% 10%
60%32% 8%
p=0.035
LAP07:ImpactofC-RTonlocalcontrol?
Commentaméliorerlecontrollocal?
Doubletoutriplet?
CA19-9, carbohydrate antigen 19-9; CT, computed tomography; HR, hazard ratio; IV, intravenous; KPS, Karnofsky performance status; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; MRI, magnetic resonance imaging; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; qw 3/4, first 3 of 4 weeks; qw 7/8, first 7 of 8 weeks; RECIST, Response Evaluation Criteria In Solid Tumors; ULN, upper limit of normal.
• Primary endpoint– OS
• Secondary endpoints– PFS and ORR by independent
review (RECIST v1.0)• Safety and tolerability
– By NCI CTCAE v3.0
• With 608 events, 90% power to detect OS HR = 0.769 (2-sided α = 0.049)
• Treat until progression or unacceptable toxicity• Spiral CT or MRI scans every 8 weeks• CA19-9 measurements at baseline and every
8 weeks
Von Hoff DD, et al. N Engl J Med. 2013 Oct 16. [Epub ahead of print]. 32
Phase III Gemcitabine + nab-Paclitaxel in Metastatic Pancreatic Cancer: Study Design
a The 75th percentile represents the time point at which 25% of patients were alive.Gem, gemcitabine; HR, hazard ratio; nab-P, nab-paclitaxel; OS, overall survival; pt, patient. Von Hoff DD, et al. N Engl J Med. 2013;369(18):1691-1703. 33
Phase III Gemcitabine + nab-Paclitaxel in Metastatic Pancreatic Cancer: Overall Survival
nab-P + Gem(n = 431)
Gem(n = 430)
HR/RRR (95% CI) P Value
OS, median monthsOS rate, %12 months 24 months
8.5
359
6.7
224
0.72 (0.62 - 0.83) < 0.001
PFS, median monthsPFS rate, %6 months12 months
5.5
4416
3.7
259
0.69 (0.58 - 0.82) < 0.001
ORR by independent review, %ORR by investigator review, %
2329
78
3.19 (2.18 - 4.66)3.81 (2.66 - 5.46)
< 0.001< 0.001
DCR by independent review, % 48 33 1.46 (1.23 - 1.72) < 0.001
TTF, median, months 5.1 3.6 0.70 (0.60 - 0.80) < 0.001
Decrease in CA19-9 level, % nab-P + Gem (n = 379)
Gem(n = 371)
≥ 20% decrease≥ 90% decrease
6131
4414
< 0.001< 0.001
Von Hoff DD, et al. N Engl J Med. 2013;369(18):1691-1703.
CA19-9, carbohydrate antigen 19-9; DCR, disease control ratio; Gem, gemcitabine; HR, hazard ratio; nab-P, nab-paclitaxel; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; RRR, relative risk ratio; TTF, time to treatment failure.
34
Phase III Gemcitabine + nab-Paclitaxel in Metastatic Pancreatic Cancer: Efficacy Outcomes
CA046 (Lopez-Martín): Subgroup Analysis of Outcomes of the MPACT Trial Based on Primary Tumor LocationEfficacy by Primary Tumor Location Summary
Efficacy Parameter nab-P + Gemn = 431
Gem n = 430 HR or RRR P Value
Tumor location: headn (%) 191 (44) 180 (42) —
OS, median, months 9.3 6.5 0.59 < 0.001
PFS, median, months 5.5 3.7 0.53 < 0.001
ORR, % 25.0 5.0 5.03 < 0.001Tumor location: othern (%)a 237 (55) 246 (57) —OS, median, months 8.1 6.9 0.80 0.033PFS, median, months 5.4 3.7 0.74 0.013ORR, % 21.0 9.0 2.36 < 0.001
a n values different from at-risk populations in the previous slides because of differences in the analysis populations.
Gem, gemcitabine; HR, hazard ratio; nab-P, nab-paclitaxel; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; RRR, response rate ratio.Lopez-Martín J, Ma WW, Balcke P, et al. nab®-Paclitaxel plus gemcitabine vs gemcitabine alone for patients with metastatic pancreatic cancer: influence of primary pancreatic tumor location on efficacy and treatment exposure in the MPACT phase III trial. Poster presented at: 16th World Congress on Gastrointestinal Cancer; June 25 - 28, 2014; Barcelona, Spain [abstract P-0029]. 35
Phase II/III FOLFIRINOX in Metastatic Pancreatic Cancer: Study Design
Conroy T, et al. N Engl J Med. 2011;364:1817-1825.
5-FU, 5-fluorouracil; ECOG, Eastern Cooperative Oncology Group; IV, intravenous; OS, overall survival; PFS, progression-free survival; PS, performance status; q2w, every 2 weeks, qw 3/4, first 3 of 4 weeks; qw 7/8, first 7 of 8 weeks.
Phase II§ Primary endpoint: tumor response§ Secondary end point: safetyPhase III• Primary endpoint: OS• Secondary endpoints: PFS, tumor response, safety, quality of life
36
FOLFIRINOX, 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; Gem, gemcitabine; HR, hazard ratio; OS, overall survival; Pts, patients.
• Subsequent therapy: 80 patients for FOLFIRINOX and 85 for Gem• Median survival was 4.4 months in both groups from the time of secondary therapy
Phase II/III FOLFIRINOX in Metastatic Pancreatic Cancer: Overall Survival
37Conroy T, et al. N Engl J Med. 2011;364:1817-1825.
Intent-to-Treat FOLFIRINOX(n = 171)
Gem(n = 171)
HR (95% CI) P Value
OS, median, monthsOS rate, %6 months12 months 18 months
11.1
75.948.418.6
6.8
57.620.66.0
0.57(0.45 - 0.73)
< 0.001
PFS, median, monthsPFS rate, %6 months12 months18 months
6.4
52.812.13.3
3.3
17.23.50
0.47(0.37 - 0.59)
< 0.001
ORR, % 31.6 9.4 NA < 0.001DCR, % 70.2 50.9 NA < 0.001Response duration,median, months 5.9 3.9 NA 0.57
Conroy T, et al. N Engl J Med. 2011;364:1817-1825.
DCR, disease control rate; FOLFIRINOX, 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; Gem, gemcitabine; HR, hazard ratio; NA, not available; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.
Phase II/III FOLFIRINOX in Metastatic Pancreatic Cancer: Efficacy Outcomes
38
However, no data in the NEJM paper on the local pancreatic tumor mass control rate
First Author
No. of Pts with
Metastatic Disease
FOLFIRINOX Regimen/Deliverya5Efficacyb Safety
OSmos
PFS mos
ORR%
Select Grade ≥3 AEs,g(%)
Gunturu1 19c Same starting dose used as reported by Conroy et al.5 All pts received pegfilgrastim; Lower median relative dose intensities vs Conroy et al5 for irinotecan (64% vs 81%) and bolus 5-FU (66% vs 82%)
11.2 9.9 47 Neutropenia (11.4),fatigue (5.7), diarrhea, (2.9),febrile neutropenia (2.9)
Lowery2 61d Median starting dose was 80% as reported by Conroy et al5; prophylactic growth factor was given in 84% of pts
12.5 NR 40 Neuropathy (15),myelosuppression (7)
Mahaseth3 28 Omitted bolus 5-FU, included mandatory G-CSF
NRf NRf 21 Fatigue (11), diarrhea (11), neuropathy (4), neutropenia (4)
Vaccaro4 36e Starting dose undefined; 58% received prophylactic G-CSF; FOLFIRINOX dose was reduced to 75% in 23% of cycles
NA 8g 25g Neutropenia (16.6)
Modified FOLFIRINOX in Advanced Pancreatic Cancer: Retrospective Analysis
1. Gunturu KS, et al. Med Oncol. 2013;30:361. 2. Lowery MA, et al. J Poster presented at: ASCO 2012. [abstract 4057]. 3. Mahaseth H, et al. Abstract presented at: ASCO 2012. [abstract e14614]. 4. Vaccaro V, et al. Abstract presented at: ASCO 2012. [abstract e14661]. 5. Conroy T, et al. N Engl J Med. 2011;364:1817-1825.
5-FU, 5-fluorouracil; AE, adverse event; DCR, disease control rate; FOLFIRINOX, 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; G-CSF, granulocyte colony-stimulating factor; mos, months; NA, not available; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; pts, patients.
a Modified based on Conroy study regimen; b OS and PFS given as median; outcomes for pts with metastatic disease only unless otherwise indicated; c Of the 35 pts were treated, 19 had metastatic disease and 17 pts were evaluable for efficacy; d Of the 80 pts enrolled, 61 had metastatic disease; e Identified as advanced, inoperable pancreatic cancer; 26 pts had metastatic disease. PFS and ORR apply to all 36 pts; fMedian OS and PFS were NR after median 5.5 months follow-up; g In all treated pts.
39
FirstAuthor
No. of Pts with
Metastatic Disease
FOLFIRINOX Regimen/Deliverya4
Efficacyb Safety
OS mos
PFS mos
ORR %
Select Grade ≥3 AEs,g (%)
Peddi1 38c FOLFIRINOX5 regimen modified in 51% of pts; 22 pts did not receive 5-FU; irinotecan DR required in 22 pts; 67% of pts received G-CSF starting in cycle 1
1 yr OS: 42%
NA 18 Neutropenia (19.7), abdominal pain, (8.2), fatigue (4.9), febrile neutropenia (4.9), diarrhea (3.3)
Ginocchi2 17d No bolus 5-FU and lower dose of irinotecan (150 mg/m2 q2w); modified dose of infusional 5-FU (2800 mg/m2 over 48 hours q2w). 18% pts received G-CSF
14.8 8.4 33 Neutropenia (35.9), neuropathy (5.1), diarrhea (5.5), fatigue (2.6)
Alessandretti3 19e No bolus 5-FU and DR of at least 1 agent at cycle 1. 73% of pts received prophylactic G-CSF . Median DR cycle 1: 23% for oxaliplatin, 25% irinotecan, and 21% 5-FU
NRf NRf 32g Neutropenia (21%), fatigue (15.7%), diarrhea (5.2), febrile neutropenia (15.6%)
Modified FOLFIRINOX in Advanced Pancreatic Cancer: Retrospective Analysis (cont)
1. Peddi PF, et al. JOP. 2012;13:497-501. 2. Ginocchi L, et al. Presented at ESMO 2012. [abstract 714P]. 3. Alessandretti , et al. Abstract presented at : ASCO 2013. [abstract e15176]. 4. Conroy T, et al. N Engl J Med. 2011;364:1817-1825.
5-FU, 5-fluorouracil; DCR, disease control rate; FOLFIRINOX, 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; G-CSF, granulocyte colony-stimulating factor; mos, months; NA, not available; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; pt, patients; q2w, every other week.
40
a Modified based on Conroy study regimen; b OS and PFS given as median; outcomes for pts with metastatic disease only unless otherwise indicated; c Of the 35 pts were treated, 19 had metastatic disease and 17 pts were evaluable for efficacy; d Of the 80 pts enrolled, 61 had metastatic disease; e Identified as advanced, inoperable pancreatic cancer; 26 pts had metastatic disease. PFS and ORR apply to all 36 pts; fMedian OS and PFS were NR after median 5.5 months follow-up; g In all treated pts.
First Author
No. of Pts with
Metastatic Disease
FOLFIRINOX Regimen/Deliverya6
Efficacyb Safety
OS mos
PFSmos
ORR%
Select Grade ≥3 Aes,g (%)
Lorgis1 42 Standard FOLFIRINOX6
9 NA NA
Neutropenia (57), diarrhea (30), neuropathy (25), febrile neutropenia (14)
Metges2 79 FOLFIRINOX regimen undefined; during treatment, 75% of pts had a dose adjustment
10.2 5.7 37 Total (28)
Faris3 26c FOLFIRINOX regimen undefined NA NA 33 Neutropenia (32), febrile neutropenia (16)
Arlen4 ≈ 93d,e FOLFIRINOX regimen undefined 8.4 NA NA NA
Cartwright5 522 FOLFIRINOX regimen undefined 10.2f NA NA NA
Modified FOLFIRINOX in Advanced Pancreatic Cancer: Retrospective Analysis (cont)
1. Lorgis V, et al. Anticancer Res. 2012;32:4125-4130. 2. Metges J-P, et al. Poster presentation at: ASCO 2012. [abstract 248]. 3. Faris JE, et al. Abstract presented at: ASCO 2012. [abstract e14615]. 4. Arlen AG, et al. Abstract presented at: ASCO 2012. [abstract e16536]. 5. Cartwright TH, et al. Poster presented at: ASCO 2013. [abstract 6607]. 6. Conroy T, et al. N Engl J Med. 2011;364:1817-1825.
DCR, disease control rate; FOLFIRINOX, 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; KPS, Karnofsky performance score; mos, months; NA, not available; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; pts, patients.
41
a Modified based on Conroy study regimen; b OS and PFS given as median; outcomes for pts with metastatic disease only unless otherwise indicated; c Of the 35 pts were treated, 19 had metastatic disease and 17 pts were evaluable for efficacy; d Of the 80 pts enrolled, 61 had metastatic disease; e Identified as advanced, inoperable pancreatic cancer; 26 pts had metastatic disease. PFS and ORR apply to all 36 pts; fMedian OS and PFS were NR after median 5.5 months follow-up; g In all treated pts.
FOLFIRINOXnéo-adjuvantdanslescancersdupancréasborderlines
KATHLEENK.CHRISTIANSetal.TheOncologist2014;19:266–274
Résumé:Quellechimiothérapiechoisir?
•GemcitabineMonothérapie• Peuutileennéo-adjuvantcomptetenudufaibletauxderéponse(idempourgemcitabine+erlotinib)
•FOLFIRINOX• Untauxdecontrollocaljusqu’à31.6%(18-47%)• Unprofildetolérancequirequièredespatients‘fit’
•Nab-paclitaxel +gemcitabine• Untauxderéponsede21-29%• Unprofiledetoxicitéplusfavorablequelatripletpourdespatientsplusfragiles
• NonrembourséenFrance
Conclusion
• L’objectifd’obteniruneréponseobjectivelocaleencontrôlantlamaladiemétastatiqueetenutilisantuntraitementnéoadjuvantn’estsusceptibledebénéficierqu’àunnombrelimitédepatients
• Lachimiothérapienéo-adjuvante(parFOLFIRINOX– Nabpaclitaxel/gemcitabine)peutêtreutiliséependant4moisavantlachirurgiepourpermettrelasélectiondepatientsrépondeursetégalementidentifierceuxnedéveloppantpasdemétastasesàdistancedurantcettepériode
• Pourlespatientsopérés,untraitementadjuvantpargemcitabinemonothérapieresteleseultraitementactuellementvalidédansl’attentedesrésultatsdeFOLFIRINOXadjuvant
Opérablesouborderline20-25%
100patients 25patientsRéponseàlachimiothérapie
<30%8patients Operable
?