RT/TMZ/BEV - Rencontres Cancero 2013

Modérateurs : Pr.Marc Spielmann et Pr.Hassane Errihani
•
Les Immanquables dans le colo-rectal

Pr. Eric Van Cutsem

Pr. Blaha Larbaoui
•
Les Immanquables en onco-gynécologie

Pr. Kamel Bouzid

Pr. Patricia Pautier
•
Les Immanquables dans le cancer du sein

Pr. Farhat Ben Ayed

Pr. Thierry Petit
•
Les Immanquables dans les glioblastomes

Dr. Mounir Bachouchi

Pr. Olivier Chinot
Cancers colorectaux
Pr Eric Van Cutsem et Pr Blaha Larbaoui
Maintenance treatment with capecitabine +
bevacizumab besus observation after induction
treatment with chemotherapy
+ bevacizumab in metastatic colorectal cancer
Phase 3 CAIRO3 study of Dutch Colorectal Cancer Groupe (DCCG)
Miriam Koopman, L Simkens, A ten Tije, G Creemers, O looxveld, F de Jongh, F Erdkamp,
Z erjavec, A van der Torren, J van der Hoeven, P Nieboer, J Braun, R Jansen, J Haasjes, A Cats, J
Wals, L Mol, O Dalesio, H van Tinteren, C Punt
Metastatic Colorectal Cancer maintenance trials :
from ‘stop and go’ to continuation
• Optimox : maintenance with 5FU/LV: longer PFS
• Coin, Nordic, Giscad, CONcePt : intermittent treatment may be an option
• Macro : maintenance with bevacizumab may be an appropriate option
following induction Xelox-bevacizumab
• DREAM-GERCOR : CT + bev.  bevacizumab ± erlotinib (n=650):
longer PFS for combination
• Ongoing studies with bevacizumab:
• SAKK : CT + bev.  bevacizumab vs no treatment (n=470) ASCO 2013
• CAIRO-3 : Xelox + bev.  capecitabine + bevacizumab vs no treatment
(n=635) ASCO 2013
• AIO : oxali/FU + bev.  FU/bev. vs bev. vs no treatment (n=456)
Study Design
Definition of PFS1
PFS1
Definition of PFS2
Primary endpoint
Primary endpoint PFS2
Definition of TT2PD
TT2PD
Overall survival
Conclusions - I
• Maintenance treatment with capecitabine plus bevacizumab after 6 cycles
CAPOX-B is feasible, and significantly prolongs PFS1 and PFS2
• The number of patients that was eligible for re-introduction of CAPOX-B
is lower than expected
• When any treatment after PFS1 is considered, maintenance treatment
also significantly prolongs the time to second progression (TT2PD)
• There is a non-significant benefit, which is significant in the adjusted
analysis
Bevacizumab continuation versus no continuation
ofter first-line chemo-bevacizumab therapy in
patients with metastatic colorectal cancer :
a randomized phase III non-inferiority trial
Swiss Group for Clinical Cancer Research
Koeberle D, Betticher D, von Moos R, Dietrich D, Brauchli P, Baertschi D, Matter K, Winterhalder R,
Borner M, Anchisi S, Moosmann P, Kollar A, Saletti P, Roth A, Frueh M, Kueng M, Popescu R,
Schacher S, Hess V, Herrmann R
Highlights in Neuro-Oncology
at ASCO 2013
Olivier Chinot
Aix-Marseille Université
AP-HM, Centre Hospitalo-Universitaire Timone
Service de Neuro-Oncologie
Marseille
Glioblastoma: an unmet medical need
• Tumeur cérébrale maligne la
plus fréquente
 Incidence: 13 000/an (Europe)
• Standard de traitement
inchangé depuis 2005
 RT + TMZ
• Pronostic grave
 PFS: 6.5 mois; OS 14.5 mois
• Impact fonctionnel marqué
 Autonomie, cognition, QOL
ASCO 2013 in CNS tumors :
un changement des standards de traitement ?
• Bevacizumab in GBM: Faits et controverses




Quelle Efficacité?
Quel bénéfice clinique?
Quand traiter: première ou deuxième ligne?
Qui bénéficie ?
• Nouvelles molécules
 Cibles
 Stratégies de développement
 Signaux observés
• Tumeurs rares
 PCNSL et autres tumeurs rares
• Micellanous
Targeting VEGF in GBM: Rational
Bevacizumab +/- irinotecan a strong signal of activity
in recurrent GBM
n
PFS
6mths, %
Median PFS
months
Median OS
months
4.2
9.3
5.6
8.8
4.3
1.6
7.1
6
2
6.0
Response
rate, %
bevacizumab
Cloughesy
2008
85
43
28
Bevacizumab + irinotecan
82
50
38
Historical controls
Wick, 2010
(CCNU)
92
Wong, 1999
225
Cloughesy, et al. ASCO 2008; Wick, JCO 2010; Wong, et al. JCO 1999
15
First proper controlled study of BEV in recurrent GBM
Recurrent GBM
Unmethylated MGMT
N=153
CCNU: 90-110 mg/m2 q6w
N=50
BEV 10 mg/kg q2w
N=46
1/1/1
CCNU: 90-110 mg/m2 q6w
+ BEV 10 mg/kg q2w
%9 mo OS (95% CI)
Med PFS (mo)
% 6mo PFS (95% CI)
Lomustine
43% (29-57)
2
11 (4-22)
BEV
38% (25-51)
3
18 (9-30)
BEV + lomustine
59% (43-72)
4
41 (26-55)
treatment
N=52
• BEV+CCNU atteint l’objectif fixé
• Conduit à une étude EORTC : CCNU versus CCNU+BEV
Taal et al. Abstract 2001 ASCO 2013
RTOG et AVAglio Study Design
n=463
Randomization
N=921
Debulking
surgery
or biopsy
Stratification
• RPA class
• Region
•MGMT
n=458
Treatment start
4–7 weeks post-surgery
RT
2Gy; 5 days/week
TMZ
75mg/m² qd
TMZ
150–200mg/m²
qd days 1–5
q28d
Placebo
q2w
Placebo
q2w
RT
2Gy; 5 days/week
TMZ
75mg/m² qd
TMZ
150–200mg/m²
qd days 1–5
q28d
BEV
10mg/kg q2w
BEV
10mg/kg q2w
Concurrent phase
6 weeks
Tx break
4 weeks
Placebo
q3w
BEV
15mg/kg
q3w
Maintenance phase Monotherapy phase
6 cycles 12 cycles
until PD
Co-primary objectives: inv PFS and OS; Secondary objectives: PFS (IRF); QOL; toxicity
Last patient in: March 2011
Tx = treatment; qd = daily; q28d = every 28 days; q2w = every 2 weeks; q3w = every 3 weeks
Investigator-Assessed PFS (Co-Primary Endpoint)
RT/TMZ/Plb (n=463)
Patients with an event = 387
1.0
Probability of PFS
RT/TMZ/BEV (n=458)
0.9
0.8
Patients with an event = 354
Stratified HR: 0.64 (95% CI: 0.55–0.74)
p<0.0001 (log-rank test)
0.7
0.6
RTOG: 7.3 vs 10.7 mo; p=0.004
0.5
0.4
0.3
0.2
0.1
6.2 mo
0.0
0
3
10.6 mo
6
9
12
15
18
21
24
27
30
33
36
23
25
8
13
4
2
0
1
0
0
0
0
Months
N at risk
RT/TMZ/Plb
RT/TMZ/BEV
463
458
349
424
247
366
170
278
110
189
77
104
47
71
Overall Survival (Co-Primary Endpoint)
RT/TMZ/BEV
(n=458)
346
333
Patients with
an event, n
Stratified HR
(95% CI)
p-value
(log-rank test)
RTOG: 16.1 vs 15.7 mo; p=0.11
1.0
Probability of Survival
RT/TMZ/Plb
(n=463)
0.88 (0.76–1.02)
0.0987
1-year
survival rate,
% (95% CI)
0.9
0.8
66 (62–71)
p-value
0.7
0.049
2-year
survival rate,
% (95% CI)
0.6
0.5
30 (26–34)
p-value
0.4
72 (68–77)
34 (29–38)
0.235
0.3
0.2
0.1
16.7 mo
0.0
N at risk
RT/TMZ/Plb
RT/TMZ/BEV
0
3
6
9
463
458
444
440
405
421
355
387
12
293
322
15
245
253
16.8 mo
18
201
203
21 24
Months
163
176
118
139
27
84
91
BEV = bevacizumab; CI = confidence interval; HR = hazard ratio; mo = months;
Plb = placebo; RT = radiotherapy; TMZ = temozolomide
30
33
36
39
42
45
53
61
28
27
15
11
6
4
0
1
0
0
Mean Change From Baseline : Global Health Status
• No difference between arms in mean change from baseline, at any
single time point for all scales
Wks = weeks
Functional Independence
A. Median duration of KPS ≥70*
during progression-free survival
B.Time until KPS deterioration of ≥20
points (ITT)
RT/TMZ/BEV (n=458)
6
KPS ≥70
0
9
2
4
6
Months
8
10
Proportion with
Definitive deterioration
RT/TMZ/Plb (n=463)
1.0
Stratified HR: 0.65 (95% CI: 0.56–0.75)
p<0.0001 (log-rank test)
0.8
0.6
0.4
0.2
N at risk
RT/TMZ/Plb
RT/TMZ/BEV
9.0 mo
5.5 mo
0
0
3
6
9
463
458
314
386
199
306
132
221
*KPS ≥70 indicating maintenance of functional independence in activities of daily living
12 15 18 21 24 27 30 33 36
Months
89
151
60
87
36
55
15
21
5
11
2
3
1
1
0
0
0
0
Time to Steroid Initiation for Patients OFF Steroids at Baseline
Initiation of corticosteroid therapy
RT/TMZ/Plb (n=253)
RT/TMZ/BEV (n=269)
1.0
0.9
0.8
Stratified HR: 0.71 (95% CI: 0.57–0.88)
p=0.0018 (log-rank test)
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
N at risk
RT/TMZ/Plb
RT/TMZ/BEV
3.7 mo
12.3 mo
0
3
6
9
12
15
253
269
133
179
106
163
88
146
77
125
56
76
18
21
Months
34
47
17
20
24
27
30
33
36
5
11
2
5
1
0
0
0
0
0
BEV = bevacizumab; CI = confidence interval; HR = hazard ratio; mo = months; Plb = placebo; RT = radiotherapy; TMZ = temozolomide
Chinot, et al. SNO 2012
Investigator-Assessed PFS: Subgroup Analyses*
Category
Subgroup
All
Bevacizumab better
Placebo better
N
All
Age, years
<50
50–59
60–69
≥70
HR#
95% CI
921 0.65
0.56–0.75
229
323
296
73
0.64
0.69
0.59
0.78
0
1–2
465 0.71
455 0.57
0.47–0.86
0.54–0.88
0.46–0.77
0.46–1.33
0.58–0.88
0.46–0.69
III
IV
V
151 0.64
540 0.62
229 0.72
0.44–0.93
0.51–0.74
0.54–0.96
Methylated
Non-methylated
Missing
237 0.76
461 0.56
223 0.61
0.56–1.04
0.46–0.68
0.46–0.82
Biopsy only
Partial/complete resection
104 0.81
817 0.62
0.53–1.26
0.54–0.73
MMSE score
<27
≥27
214 0.74
696 0.63
0.55–0.99
0.53–0.75
Corticosteroid use at baseline
On
Off
395 0.69
522 0.63
0.55–0.85
0.51–0.76
WHO PS
RPA class
MGMT gene promoter status
Surgical status
HR
0.1
0.2
0.4 0.6 1
2
3 4 56
10
20
*Selected subgroups only; #Unstratified analysis
CI = confidence interval; HR = hazard ratio; MGMT = methylguanine-DNA methyltransferase; MMSE = mini-mental state examination;
PFS = progression-free survival; RPA = recursive partitioning analysis; WHO PS = World Health Organization performance status
GBM with unmethylated MGMT BEV+IRI+RT vs TMZ+RT
N=116
GBM newly diagnosed
Unmethylated MGMT
N=170
RT + TMZ concomittant
Then 6 cycles TMZ 5 days q4w
2/1
N=54
RT + BEV 10 mg/kg + IRI 125 mg/m2 q2w
Then BEV 10 mg/kg + IRI 125 mg/m2 q2w
• Étude positive pour son critère principal : PFS6 :
• PFS6 (IRF) : 71.1% (95%CI 58.1-80.8)
vs 26.2% (95%CI 13.1-41.4%) ; p<0.0001
Herlinguer et al. Abstract LBA2000 ASCO 2013
GBM in the elderly with poor functional status
BEV+TMZ exclusive
GBM newly diagnosed
Age>70y
KPS<70
N=66
TMZ 150-200 mg/m2 day 1-5 q4w
+ BEV 10 mg/kg q2w
• Etude de phase II, contrôle historique: essai TAG (JCO 2012)
• Objectif principal: SG médiane:24 w (95% CI, 19-27.6)
• Objectifs secondaires:
 PFS médiane: 16 w (95% CI, 13.1-19.3)
 Amélioration fonctionnelle (KPS>70): 38%
 Toxicité grade 3-4: hématologique 19.6%; non hématologique 32%
• Pas de bénéfice détectable à l’adjonction de BEV au TMZ
Reyes-Botero et al. Abstract 2020 ASCO 2013
Bev biomarkers
• Avaglio, (Nishikawa, abstract 2023)
 Baseline plasma VEGF et VEGFR2 sans valeur prédictive sur la PFS
• RTOG 0825, (Sulman, abstract LBA 2010)
 Signature intra-tumorale 9 gènes: impact douteux
• Étude rétrospective, (Di Stephano, abstract 2028)
 Polymorphisme du VEGF (CC genotype de rs2010963) corrélé à la toxicité
thromboembolique
• Etude prospec-rétro (Tabouret, abstract 2024)
 MMP2 marqueur prédictif de l’efficacité du BEV
PFS and OS according to baseline MMP2 plasma level
Median
MMP2
227.5.ng/ml
Bev prospective
Tabouret et al. Abstract 2024 ASCO 2013
185.2 ng/ml
Bev retrospective
178.5 ng/ml
Cytotoxic retrospective
Other targets/drugs then bevacizumab
• intégrines: cilengitine (Stupp, LBA 2009)
 Phase III vs SOC, GBM nouvellement diagnostiqués MGMT méthylé: négative
• Inhibiteur PI3K,
 SAR245409 (Cloughesy, abstract 2015)
 BKM120 (Wen, abstract 2015)
• Histone deacetylase: panobistat+BEV (Lee, abstract 2013)
 Efficacité modeste/ non détectée en combinaison
• Sorafenib+ temsirolimus (Jaeckle, abstract 2014)
•
Efficacité modeste/ non détectée après échappement au BEV
• TGFβ: LY 2157299 (Rodon, abstract 2018)
 Étude de PK et PD; phase II en cours
Conclusions
• L’ASCO 2013 a été dominé par les études portant sur le
bevacizumab
• L’efficacité du BEV sur les GBM est documentée par deux essais de
phase III en première ligne;
 un bénéfice clinique est observé dans Avaglio
 la toxicité est en accord avec le profil connu dans les autres cancers
• L’analyse plus complète des données de ces deux essais est
attendue (ECCO, SNO)
• La séquence thérapeutique n’est pas encore clairement établie
• La recherche de biomarqueurs reste nécessaire
• En phase III, cediranib, cilengitine n’ont pas démontré d’efficacité
sur les GBM
• Le développement de phases I/II de nouvelles molécules s’intensifie
Cancers gynécologiques
Pr Kamel BOUZID et Dr Patricia PAUTIER
Cancer du col
• prévention A 2
• traitement des formes localement avancées A5506• Les formes métastatiques A3
eros et accumsan et iusto odio dignissim qui blandit praesent
Global Burden of Cervical Cancer
Numbers indicate cases per 100,000 population
Schiffman M, Castle PE. N Engl J Med 2005;353:2101-4.
Bill & Melinda Gates Foundation (www.gatesfoundation.org)
Presented by: Krishnansu S. Tewari, MD, FACOG, FACS
Cancer du col
•
A 2 : effet de l’ex à l’AA sur la mortalité par K du col en Inde
•
500 000 nouveaux cas/an monde 30% en Inde (142000 cas)
•
 250 000 décès, 70 000 en Inde
•
Aucun accès à la prévention ni au dépistage
•
Inspection visuelle après AA (VIA): ex simple, immédiat, faisable par
personnel paramédical formé en 4 sem
eros et accumsan et iusto odio dignissim qui blandit praesent
Cancer du col : Prévention
Dépistage x 4
Biannuel 2 ans
 150 000 femmes
L Préinv
LSIL
219
35
HSIL
109
13
Cancer du col
75360 femmes
Education
VIA
Ex clinique
VIA + : biopsie
76178 femmes
Education
Ex Clinique
< IIIB
50
24
≥ IIIB
87
100
Mortalité
par K du
col
67
98
Réduction de 30%
de la mortalité par K du col
eros et accumsan et iusto odio dignissim qui blandit praesent
Cancer du col : Immunothérapie
eros et accumsan et iusto odio dignissim qui blandit praesent
Cancer du col : Immunothérapie
NS : pas autant d’évènements que prévu (trop de st II); mixte RT et RT-CT
eros et accumsan et iusto odio dignissim qui blandit praesent
Cancer du col métastatique
•
Adjonction beva à la CT?
•
Intérêt d’une bithérapie sans platine?
•
n= 452; stratification CDDP avec RT
Cis + Pac
(n= 229)
Topo + Pac
(n= 223)
81 (35)
93 (42)
15
12.5
Events, n (%)
Median OS, mos
HR=1.20 (98.74% CI; 0.82–1.76)
P (one-sided)=0.880
Topotécan Taxol non différent de CDDP Taxol
eros et accumsan et iusto odio dignissim qui blandit praesent
GOG 240 : OS for Chemo vs Chemo + Bev
Proportion Surviving
1.0
0.9
Events, n (%)
0.8
Median OS,
mos
0.7
Chemotherapy
(n=225)
Chemotherapy
+ Bev (n=227)
140 (62)
131 (58)
13.3
17.0
HR=0.71 (97% CI, 0.54-0.94)
P=0.0035
0.6
Median follow-up
0.5
0.4
0.3
0.2
0.1
0.0
0
Perfo 3%, Fistules 2%,
thromboses 8%, HTA 25%
12
Months on Study
Presented by: Krishnansu S. Tewari, MD, FACOG, FACS
24
36
20.8 mos
Cancer de l’ovaire
•
LBA5503
•
5513
•
5514
•
5516
eros et accumsan et iusto odio dignissim qui blandit praesent
Antiangiogéniques et cancer de l’ovaire
• Confirme l’intérêt des anti-angiogéniques en consolidation
•
2 ans vs 1 an, profil de toxicité
• Signature gènes angiogénèse pronostique dans les HGSC A 5509
Antiangiogéniques et cancer de l’ovaire
Autres Négatifs :
•Ombrabuline mPFS 10,4
mo (plac) vs 8,4 mo : A
5515
•Sorafenib : (A 5513) : PFS
2 ans 39 et 40%
Facteurs biologiques :
prédictifs et pronostics
Nouvelles classifications moléculaires
• Ovaire A 5510 Konecny
 Confirmation de la signature génique du cancer genome atlas
•
Immunoreactive like
•
Differenciated like
•
Proliferative like
•
Stromal like
pronostic
(TCGA) avec classification par groupe de gènes pour les HGS avec
valeur pronostique et peut être thérapeutique
• Endomètre A 5511
• Nbe copies d’altérations des gènes Pic
eros et accumsan et iusto odio dignissim qui blandit praesent
Nouvelles thérapeutiques ciblées A 5505, A5504 : PARP inhibition and
homologous recombination (HR) repair deficiency in ovarian cancer
•
PARP inihibitors prevent the repair of single-strand DNA breaks in tumours with
HR deficiences, leading to cell death
•
10-15% of epithelial ovarian cancers are deficient in HR repair owing to germine
BRCA1 or BRCA2 mutations1
•
Up to 50% of patient with high-grade serous ovarian cancer could be deficient in
HR repair due to2 :

Germine or somatically acquired BRCA1 or BRCA2 mutations

Epigenetic inactivation of BRCA1

BRCA1-BRCA2-independent defects in the HR pathway
•
Phase I/II trials have previously shown that olaparib is active in patients with
BRCA1/2-mutated or sporadic, high-grade serous ovarian cancer
1. Bast JR, RC et al. Nat Rev Cancer 2009;9.415-428; 2. Press JZ et al. BMC Cancer 2008;8:17; 3.
Fong PC et al. N Engl J Med 2009; 361:123-134; 4. Gelmon KA et al. Lancet Oncol 2011; 12:852-861
Nouvelles thérapeutiques ciblées A 5505, A5504 :
Background
• FOXM1 is a transcription
factor normally repressed
by wild TP53
• TP53 mutations contribute
to the overexpression of
FOWM1 and its
proliferation-related target
genes, including Plk1
Nouvelles thérapeutiques ciblées A 5505, A5504 :
PFS by BRCAm status
• 82% reduction in risk of disease progression or death with olaparib
Nouvelles thérapeutiques ciblées A 5505, A5504 :
Primary efficacy endpoint
Dépistage A 5507 5508 : UK FOCSS Phases
• Phase 1
• Phase 2
 2002 – 2007/8
 2007/8 – 2012
 Annual screening
 4-monthly screening
 Local delivery
 Centralised delivery (webbased)
 CA125 cut-off
 Risk of Ovarian Cancer
Algorithm (ROCA)
Dépistage A 5507 5508 : Objective
• To compare IHC, MSI testing, tumour morphology and family
history to germline mutation status to determine which screening
strategy is superior at identifying those at risk for Lynch
Syndrome in unselected women with endometrial cancer
Dépistage A 5507 5508 : Conclusions from Phase 2
• 4-monthly screening for familial OC has
 Acceptable overall sensitivity (75-100%)
 PPV (13%) lower than Phase 1 (reflects lower referral threshold)
• Proportion of early stage cancers still disappointing and not
significantly better than with annual screening
• Use of call and recall system reduced avoidable delays
(by median 96 days)
• Improved survival if screened regularly or just lead time bias ?
Dépistage A 5507 5508 : Conclusions
• 17% suspected Lynch Syndrome
• Germline mutation rate at least 5%
• LS Morphologic features not adequate screening strategy
• Current family history criteria miss significant proportion of
women with LS
• EC was the sentinel cancer in majority of women with LS
Cancers du sein
Pr Farhat BENAYAD et Pr Thierry PETIT
Apprendre et reproduire
Cancers du sein
Phase néo-adjuvante
ACOSOG Z1041 (Alliance) : Definitive analysis of
randomized neoadjuvant trial comparing FEC
followed by Paclitaxel plus Trastuzumab
(FEC  P+T) with Paclitaxel plus Trastuzumab
followed by FEC plus Trastuzumab
(P=T  FET + T) in HER2+ operable Breast Cancer
A. Buzdar, V. Suman, F. Meric-Bernstam, M. Leitch, M. Ellis, J. Boughey; G. Unzeitig; M. Royce; K.
Hunt on behalf of ACOSOG Investigators
ACOSOG Z1041
Pathological Response Rates in the Breast
Arm 1
N = 138
Arm 2
N = 142
P-value
pCR in breast
56,5%
54,2%
0,72
95% CI
47,8-64,9%
45,7-62,6%
Pathological Response Rates in the Breast and Axilla among
cN1-3 patients
Arm 1
N = 89
Arm 2
N = 90
pCR in breast and
axilla
48,3%
46,7%
95% CI
37,6-59,2%
36,4-56,9%
P-value
0,88
A Randomized phase II trial investigating
the addition of carboplatin to neoadjuvant therapy
for triple-negative and HER2-positive early breast cancer
(GeparSixto – GBG 66)
Gunter von Minckwitz; Andreas Schneeweiss; Christoph T.Salat; Mahdi Rezai; Dirk M. Zahm; Peter
Klare; Jens U.Blohmer; Hans Tesch; Fariba Khandan; Sebastian Jus; Christian Jackisch; Keyur
Mehta; Valentina Nekljudova; Sibylle Loibl; Michael Untch
for the GBG/AGO-B study groups
Chemotherapy regimen
pCR Rates by Subtype
Impact of Neoadjuvant Chemotherapy
Plus HER2-targeting on
Breast Conservation Rates :
Surgical Results from CALGB 40601
David W. Ollila; Donald A. Berry; Constance Cirricione; Lisa A. Carey; Keith D. Amos; Norah Lynn
Henry; Eric P. Winer; Clifford Hudis; Mehra Golshan; Alliance for clinical Trials on Oncology; The
University of North Carolina at Chapel Hill; Chapel Hill, NC; The University of Texas MD Andreson
Cancer Center, Houston, TX; Alliance Statistical Canter, Duke University, Durham, NC; University
of Michigan Medical Center, New York, NY; Brigham and Women’s Hospital, Boston, MA
Pathologic Complete Response (pCR)
Cancers du sein
Phase adjuvante
CALGB 40101 – Protocol Schema
4 vs 6 Cycles of Therapy – Previously Reported
4-yr RFS
6 cycles
4 cycles
90,9%
91,8%
HR of 6:4
(95% CI)
P
1,03
(0,84-1,28)
0,77
4-yr OS
95,3%
96,3%
HR of 6:4
(95% CI)
P
1,12
(0,84-1,49)
0,44
Relapse-Free Survival
aTTom : 10 vs 5 Years Tamoxifen N = 6953
• Recurrence RR = 0,85
(95% CI 0,76-0,95; p = 0,003)
 Absolute reducation 4%
• Breast Cancer Mortality RR = 0,88
 Absolute reduction 2%
Grav et al., Abstract5. ASCO 2013
(95% CI 0,77-1,01; p = 0,06)