cancer du sein et sujet âgé - longuevieetautonomie.fr · oncologie médicale hôpital rené...
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Cancer du sein et sujet âgéCancer du sein et sujet âgé
Docteur Etienne BrainOncologie Médicale
Hôpital René Huguenin / Institut CurieSaint-Cloud, France
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A frailty revealed…
• 2006: Mrs BON… IR… 84 yo– No previous medical history (high blood sugar?)– Husband: 86 yo w/ severe advanced Parkinson, 2 children– Breast self exam � T1c N0 M0 left breast– 54 kg/167 cm
• Conservative surgery + axillary lymph node dissection• Conservative surgery + axillary lymph node dissection– Invasive ductal carcinoma, 17 mm, SBR II, 8 N-– ER- PgR-, Ki 67 40%, HER2-
• Adjuvant strategy– Chemotherapy with anthracylines (GERICO 06)? + XRT
• Scoring– Oncologist: PS 0 � “Easy! Go for it“– Geriatrician
• Functional status, cognition, nutrition, GDS � OK• However ! 3 falls < 1 year
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… treatment decision process
• LVEF by MUGA scan normal• Not in GERICO 06 trial, but OK for the oncology staff!• The lady “accepted”….
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… treatment decision process & respect
• LVEF by MUGA scan normal• Not in GERICO 06 trial, but OK for the oncology staff!• The lady “accepted”…. but DID she?
• Central venous access + 1 cycle of AC-like chemo �• Central venous access + 1 cycle of AC-like chemo �febrile neutropenia + severe stroke (cardiac arythmia?)– Chemotherapy stopped– Husband placed in nursing home– Delayed XRT– Recovered with neurological sequelae– Seniors residence– No relapse so far (last visit early 2015)
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Pelike from Attica480–470 BC
Musée du Louvre
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Pourquoi cette question ?
1. Le nihilisme thérapeutique : les sujets âgés ne reçoivent pas de traitement
2. La nuance : les sujets âgés peuvent bénéficier des traitementsdes traitements
3. L’enthousiasme thérapeutique aveugle : les sujets âgés reçoivent un traitement « futile »
� � � Places du gériatre et de l’oncologue
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2009
2050
http://www.un.org/esa/population/publications/ageing/ageing2009chart.pdf
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Projected number of cancer cases for 2000–2050 by a ge group (<45, 45–64, 65–84, 85+) based on projected census population estimates and delay-adj usted SEER-17 cancer incidence rates
Hayat The Oncologist 2007;12:20-37©2007 by AlphaMed Press
Incidence of cancer from 2010 to 2030 (Smith JCO 2009)• +11% < 65 yo• +67% > 65 yo
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Cancer du sein - Incidence
de Vathaire FRANCIM/INSERM 1996, IVS 2003
Age 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75+ Total63.3 119.7 187.3 177.3 182.8 211.3 220 231.1 220.4 89.2
40% ou 25% x 1.5 en 2030 ?
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De Angelis. Lancet Oncol 2013
Relative survival accounts for mortality from causes other than the relevant cancer, which can vary widely between countries
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• Most common shortcut in statistics“1 in 8 women will develop BC in their lifetime”
instead of“If everyone lived beyond the age of 70, 1 in 8 of those women
would get or have had BC”• Since BC risk increases w/ age, lifetime risk changes depending on age
– Age 20-29 1 in 2,000– Age 30-39 1 in 229– Age 30-39 1 in 229– Age 40-49 1 in 68– Age 50-59 1 in 37– Age 60-69 1 in 26– Ever 1 in 8
Worldwidebreastcancer.com/breast-cancer-statistics- worldwide
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Phénotype
Plus de formes hormonosensibles (RH+)Moins de formes agressives (triple négatif , HER2+++)Moins de formes agressives (triple négatif , HER2+++)
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60
70
80
90
100
ER+
• 205.736 femmes, cancers du sein > 20A• SEER 1990-2000• Récepteurs hormonaux (RH)
� Aux oestrogènes (RO ou RE, ou ER en anglais) et à la progestérone (RP ou PgR en anglais)� Négatifs (RH-) si tous les 2 sont absents� Positifs (RH+) si l’un ou l’autre est présent (RO ou RP)
0
10
20
30
40
50
20 - 29 30 - 39 40 - 49 50 - 59 60 - 69 70 - 79 > 80
PgR+ER-PgR-
Age
Grann Cancer 2005
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RO RP HER2 CK5-6/EGFR Ki67
Luminal A ++ ++ - - -
Luminal B ++ +/- - - +
Basal-like = triple négatif - - - + +
HER2 +/- +/- + -/+ +
La « nouvelle » classification
HER2 +/- +/- + -/+ +
Normal breast-like + + - -/+ -/+
Claudin-low +/- +/- -/+ +/- +/-
Apocrine - - +/- -/+ +
Perou, Nature 2000 ; Sorlie, PNAS 2001 & 2003 ; Sot iriou, PNAS 2003Reis Filho, Lancet 2011
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Cheang, Clin Cancer Res 2008; Durbecq, CROH 2008
• British Columbia Cancer Agency• 1986-1992• 4,046 pts
• Jules Bordet• 2,723 pts
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Dépistage
Pas d’indication d’extension du dépistage de masse > 7 4A(stades plus précoces dépistés mais aucun bénéfice démont ré sur survie)
Mais dépistage individuel à poursuivre selon état de sant é
Aucune étude conduite spécifiquement sur cette population
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Breast cancer screeningNEJM september 15,2011, Ellen Warnerno real benefit of screening after 70 years
Age N0 of trial(s) Relative risk of death
(95 CI)
60-69 yr 2 Malmö ans Ostergöland 0,68 (0,54-0,87)
70-79 1 Ostergöland 1,12 (0,73- 1,72)
17
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Age limits for BC screening
• France: 50-74 ans• Europe : idem• USA : idem• Recommandations for elderly : YES YOU • Recommandations for elderly : YES YOU
CAN…but it’s not included in THE national program
• A few ( very few) continue• The majority stops after 2 or 3 years
18
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Prise en charge initiale
Retard fréquent … d’où des stades plus tardifsRetard fréquent … d’où des stades plus tardifsDes standards fréquemment non respectés (sous-traitem ent)
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Prise en charge initiale• Registre Genève 1989-1999 : 407 sujets > 80A• Résultats
– Diagnostic tardif & bilan initial incomplet– Traitement spécifique suboptimal dans > 50% cas
Traitement % DFS5A HR (95% CI)
Bouchardy JCO 2003
Traitement % DFS5A HR (95% CI)
Aucun 12 46 1
Tamoxifène 32 51 0.4 (0.2-0.7)
Tumorectomie 7 63 0.4 (0.1-1.4)
Mastectomie 33 82 0.2 (0.1-0.7)
Tumorectomie + adjuvant 14 90 0.1 (0.03-0.4)
Divers 2 42 0.8 (0.2-2.5)
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A Population Based Study of the Management of Older Women with Breast Cancer taking into account
levels of Comorbidity
Tony Moran, Saiqa Tabasum, Christine Connor, Brian Magee, Vanessa Pope, Riccardo Audisio, Chris Holcombe, Nigel Bundred
Moran, EBCC-9, abstract 415
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Methods
� Women diagnosed in Gr Manchester, Merseyside and Cheshire in 2009 aged 60 and older
� Data collected from cancer registry and hospital notes notes
� Tumour characteristics, management and Charlson comorbidity score
� 1888 women (82% of those on registry) in study
Moran, EBCC-9, abstract 415
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Trastuzumab use60-64 yo vs 85+
36% vs 6%p<.001
Moran, EBCC-9, abstract 415
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40
60
80
100
(%)
p <0.001
Trastuzumab use60-64 yo vs 85+
36% vs 6%p<.0010
20
60-64 65-69 70-74 75-79 80-84 85+
Figure 2: Percentage of women with stage 1 or 2 dis ease and a Charlson score of 0 who underwent surgery (n=850)
Moran, EBCC-9, abstract 415
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Présentation clinique
Freyer Ann Oncol 2006
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Les traitements
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En pratique…
• 1.009 MBC65-74A 500> 75A 509
• 107 oncologues
Freyer Ann Oncol 2006
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Le cancer du sein de la femme âgée se prête volontiers à
l’hormonothérapie car il est plus souvent RH+
Mais entre anti -aromatase Mais entre anti -aromatase (letrozole/FEMARA, anastrozole/ARIMIDEX, exemestane/A ROMASINE
et anti-oestrogène (tamoxifène),la question de l’observance est majeure (et donc l’aju stement à la
tolérance)
En contexte adjuvant/précoce, l’hormonothérapie se do nne 5 ans en général (discussion sur les extensions au delà)
En contexte métastatique, l’hormonothérapie est le tra itementgénéralement de première intention (phénotype RH+ fré quent)
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Analogues dela LHRH
SERM = Anti-oestrogènesSelective Estrogen Receptor Modulators
• 35 ans d’utilisation• Standard
Déplétion en oestrogènes au mieuxréalisée par une inhibition spécifiquede l’aromatase qui convertit lesprécurseurs des oestrogènesen oestradiol et oestrone
Progestatifs
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Age Tamoxifène vs 0 Chimiothérapie vs 0
Rechute Mortalité Rechute Mortalité
< 40 44±10 39±12 40±6 29±7
Réduction (%) des risques annuels de rechute / mort alité
Leçons des méta -analyses
< 40 44±10 39±12 40±6 29±7
40-49 29±7 24±9 36±4 30±5
50-59 34±5 24±7 23±3 15±4
60-69 45±5 35±6 13±3 9±4
≥ 70 51±12 37±15 12±11 13±12
EBCTCG Lancet 1998 & 2005
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• TAM / 0
60 %
50 %
40 %
rech
ute
38,3
45,0
33,2
contrôle
TAM 5A
Réduction du risque de rechute
Bénéfice absolu à 10 ans
RO+ 41 % 13,6 %
15105
30 %
20 %
10 %
rech
ute
26,5
24,7
15,1
33,2 TAM 5A
• IA / TAM
Réduction du risque de rechute
Bénéfice absolu à 10 ans
RO+ Post-MP
20 % 5 %
AI 5A
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ATAC
BIG 1-980,82 (0,67-0,99) 0,045143<<<< 65
0,79 (0,64-0,97) 0,022867≥≥≥≥ 65
<<<< 65 5137
≥≥≥≥ 65 4229
nr nr
nr nr
HR (CI 95%) pN
Bénéfice des IA selon l’âge
0,30 0,50 0,60 0,80 1,00 1,25 1,50 2,00
ITA
0,20
≤≤≤≤ 65 nr nr
>>>> 65 nr nr
0,63 (0,40-1,00) 0,051265
≥≥≥≥ 60 0,58 (0,39-0,87) 0,081959ABCSG / ARNO
<<<< 60
nr
nr
No analysis according age in IES and ABCSG-6
TAM superiorAI superior
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Cancer controlatéralOstéoporose
MyalgiesHyperlipidémie
TAM IA
Cancer controlatéralThrombosesK endomètre
Bouffées de chaleurNeurocognitionFonction sexuelle
HyperlipidémieCardiovasculaire
?
Bouffées de chaleurThromboembolies
K endomètreSignes génitourinaires
Arthralgies/myalgiesOstéoporose
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Fractures
Etude Suivi(m)
AnnéessousTAM
IA(%)
Comparateur(%)
p
ATAC 68 0 ANA (11.0) TAM (7.7) < 0.0001
ATAC 33 0 ANA (5.9) TAM (3.7) < 0.0001ATAC
ARNO 95ABCSG 8
28 2-3 ANA (2) TAM (1) 0.015
BIG 1-98 25.8 0 LET (5.6) TAM (4.0) < 0.001
IES 55.7 2-3 EXE (7.0) TAM (4.9) 0.003
MA.17 30 4-6 LET(5.3) Placebo (4.6) 0.25
Et jusqu’à 80% d’arthralgies en plus….(20.3% vs 12.3%, p < 0.001 BIG 1-98)
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Getting a grip on aromatase inhibitor–associated arthr algiasDawn L. Hershman
Copyright © American Society of Clinical Oncology
Morales, L. et al. J Clin Oncol; 26:3147-3152 2008
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La chimiothérapie , c’est plus compliqué …
Car index thérapeutique plus étroit que l’hormonothérapieCar index thérapeutique plus étroit que l’hormonothérapie
Des doses généralement ajustées (inférieures)
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Physiological variations x PK & PD
Mechanism Consequences
AbsorptionGastric dumping and secretions �
Absorption of proteins, vitaminsand drugs �
MetabolismHepatocytes, blood flow, CYP P450 activity �Interactions (CYP P450)
Protein synthesis, (de-) activation of drugs and carcinogens �Interactions (CYP P450) carcinogens �
Distribution H2O, albumin, Hb �Vd hydrosolubles drugs �
Vd liposolubles drugs �
ExcretionGFR, tubular filtration �Biliary excretion �
Renal elimination of drugsexcreted by kidney �
Biliary elimination �
Balducci. Oncologist 2000; Wildiers. Clin Pharmacoki net 2003; http://www.ema.europa.eu
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Les grands médicaments
• Anthracyclines (adriamycine, épirubicine, schémas FEC 100 ou AC)– Myélotoxicité– Cardiotoxicité
• Alkylants (cyclophosphamide/Endoxan®, schéma FEC 100 ou AC)– Myélotoxicité– Attention à la fonction rénale
• Taxanes (docetaxel/Taxotère®, paclitaxel/Taxol®)– Myélotoxicité– Neuropathie– Onycholyse– Rétention hydrique
• Antimétabolites (5-flurorouracile, forme orale = capecitabine/Xeloda®)– Syndrome mains pieds– Diarrhée
38
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Chimiothérapie
• Des doses spécifiques– CMF et adaptation du CPA à la fonction rénale– Xeloda® 1000 mg/m² x 2/J– Taxol® < 80 mg/m²/s– Taxol® < 80 mg/m²/s– Taxotère® : PK identique mais risque accru de
neutropénie ± fièvre > 65A• q3w 75 mg/m² 63% et 16% vs 30% et 0%• qw 35 mg/m² > 50% grade ≥ 3 (RD : 26 mg/m²)• q2w 50 mg/m² GERICO-04
Gelman JCO 1984, Crivellari JCO 2000, Bajetta JCO 2005Del Mastro Ann Oncol 2005, ten Tije JCO 2005
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La chimiothérapie adjuvante « marche » si on est attentif aux
effets secondaires…effets secondaires…
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DFS
OS
• CALGB (1975-1999)• 4 randomized trials• 6487 pts
> 65 yo 542 (8%)> 70 yo 159 (2%)
Adjuvant chemo for breast cancerAll
All
≤50
≤50
≥6551-64
OS
• Results– Benefit identical– Toxicity careful!!
• Toxic deaths 1.5%
All ≤50
≥6551-64
Muss, JAMA 2005
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Cumulative proportion with event
0.8
1.0Hazard ratio (>65: ≤6≤6≤6≤65) = 2.2595% CI of (>65: ≤≤≤≤65) = (1.04–4.86)
Doxorubicine , cardiac heart failure(CHF) and ageDoxorubicine , cardiac heart failure(CHF) and age
• 630 patients (3 phase III) with 32 CHF– 26% >550 mg/m²– >50%: reduction of LVEF <30% w/CT
• HRage 2.25 (1.04–4.86) vs 3.28 (1.4–7.65) if >400 mg/m²
0
0.2
0.4
0.6
0.895% CI of (>65: ≤≤≤≤65) = (1.04–4.86)Log rank p-value = 0.029Wilcoxon p-value = 0.78
0 200 300 400 700 800 900 1000Cumulative dose of doxorubicin (mg/m 2)
600500100
468172
345110
29692
10328
61
41
203
5912
431!51
≤≤≤≤65*>65*
*Patients at risk
≤≤≤≤65
>>>>65
Swain. Cancer 2003
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Doxorubicin , CHF and age
• SEER 1992-2002: 43,338 women 66-80 years, no CHF history– stage I to III BC, chemotherapy vs no– AC: younger, fewer comorbidities, advanced (p=.001)– CHF10 years (%) AC
N = 4,712
Other chemoN = 3,921
No chemoN = 34,705
38.4 32.5 29
Pinder. J Clin Oncol 2007
38.4 32.5 29
• 66-70 years HR 1.26 (95% CI, 1.12-1.42) if AC• 71-80 years no impact of CT type
Baseline HR (95%CI)
Age (decade) 1.79 (1.66-1.93)
Black 1.40 (1.30-1.50)
Trastuzumab 1.46 (1.21-1.77)
Hypertension 1.45 (1.39-1.52)
Diabetes 1.74 (1.66-1.83)
Coronary 1.58 (1.39-1.79)
Left XRT 1.04 (0.98-1.11)
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… mais principalement si ER - !
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Giordano* Elkin
No. total
No. w/CT
I-III, ∀∀∀∀ ER , 65+41,390
4,500
I-III, ER-, 66+5,081
1,711
pN ER HR (95% IC) HR (95% IC)pN0 ∀∀∀∀ 1.05 (0.85-1.31) NA
pN+ + 1.05 (0.85-1.31) NA
Adjuvant chemotherapy and mortality
pN+ + 1.05 (0.85-1.31) NA
both - NA 0.85 (0.77-0.95)
pN+ - 0.72 (0.54-0.96) 0.76 (0.65-0.88)
pN+ > 70 yo - 0.74 (0.56-0.97)
Giordano & Elkin. J Clin Oncol 2006
Adjuvant chemo is useful FIRST
in ER-, pN0 or pN+, even > 70 yo
*: BC specific mortality
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We may try to avoid the risk of cardiotoxicity induced by
anthracyclines: TC & liposomal doxorubicin
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Fig 1. Disease-free survival (DFS) and overall surv ival (OS) (A) DFS by treatment; (B) DFS by treatmen t and age; (C) OS by treatment: 1 day; (D) OS by trea tment and age
Copyright © American Society of Clinical Oncology
Jones, S. et al. J Clin Oncol; 27:1177-1183 2009
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GERICO 06 (EUDRACT N°2005-000069-20, PHRC national 2005)
MC MC MC MC XRT± trastuzumab
if HER2+++
trastuzumabif HER2+
q3w q3w q3w
ADLTolerance
CGAADL + MNA +MMS + GDS +
CIRSG
QLQ-C30Willingness
CGAADL + MNA +MMS + GDS +
CIRSG
QLQ-C30WillingnessTolerance
CGAADL + MNA +MMS + GDS +
CIRSG
QLQ-C30WillingnessTolerance
1 & 2 yearDFS & OS
ADLTolerance
ADLTolerance
4 cycles of “AC -like” chemoIn MC, M stands for liposomal non pegylated doxorubic in
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1. Neutropénie fébrile 15%2. Risque dénutrition 15% vs 38%3. Impact QoL (social & role
functioning)4. Tolérance cardiaque du
trastuzumab5. Pas d’EPP6. DFS3A 85%
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CALGB / CTSU 49907CALGB / CTSU 49907
• 9/2001-12/2006
• 633 pts ≥ 65 yo
– 65% 70+
– 55% pT > 2 cm
– 71% pN+
– 68% ER+
• Capecitabine
– 76% compliance (> 80%)
• AC & CMF > capecitabine– Interaction +++ if ER-
– HRRFS 4.39 (95% CI: 2.9-6.7)
– HR 3.76 (95% CI: 2.23-6.34)j
> 65A6 CMF or 4 AC
6 capecitabine
– 68% ER+
• Non-inferiority trial
• Median folow up 2.4 years
• Capecitabine vs standard
– RFS3A 68% vs 85%
– OS3A 86% vs 91%
– Toxicity 33% vs 64%
– HROS 3.76 (95% CI: 2.23-6.34)j
Muss NEJM 2009
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All
DFS OSCALGB / CTSU 49907 (AC or CMF vs X)
ER-
ER+
Muss, NEJM 2009
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Kaplan–Meier survival analysis.
F. Perrone et al. Ann Oncol 2015;annonc.mdu564
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
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Mean differences in QoL scores of items presenting statistically significant differences at one or more time-points.
F. Perrone et al. Ann Oncol 2015;annonc.mdu564
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Green bars: CMFBlue bars: weekly docetaxel
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Chimiothérapie
� Rappel des recommandations précédentes pour ER- principalement�Schémas validés
� 4 AC 1A� 6 CMF 1A
�Schéma optionnel : TC� 4 TC > 4 AC 2B
– Analyse post hoc de sous-groupe d’un essai randomisé, n ~ 80– Analyse post hoc de sous-groupe d’un essai randomisé, n ~ 80
�! Capecitabine 2A� Schéma séquentiel (type 3 FEC 100 3 docetaxel)
�Pas de données� Analyse de toxicité rassurante
�TC 2B�MC 4C
� Discuter systématiquement prophylaxie primaire GCSFAccord professionnel
� Pas de restriction sur trastuzumab si chimiothérapie indiquée
Brain, Oncologie 2011
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Biganzoli, Lancet Oncol 2012
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Targeted treatments
Lack of specific data!But clinical evidence for benefit
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Ligand-bindingdomain
TGF-αEGFEpiregulinBetacellulinHB-EGFAmphiregulin
Heregulin(neuregulin-1)
Heregulin(neuregulin-1)EpiregulinHB-EGFNeuregulins-2,3,4
Tyrosinekinase
domainErb-B1EGFRHER1
Erb-B2HER2/neu
Erb-B3HER3
Erb-B4HER4
TransTrans--membranemembrane
Domaine de liaison
ATP
Domaine C Terminal(sites de phosphorylation) Transduction
du signal
Région trans-membranaire
Domaine extra-cellulaire
Domaine intra-cellulaire
Substrats deTyrosine Kinase
phosphorylés
Noyau
Membranecellulaire
LigandDomaineTyrosineKinase
Structure et fonction de l’EGF-R
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Trastuzumab
> 60 yo ≤≤≤≤ 16%
Piccart NEJM 2005
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The incidence of CHF from the Finnish Herceptin Stud y (FINHER), Herceptin Adjuvant trial (HERA), Breast Cancer International Collaborative Group trial 006 (006) with TCH and AC-TH analyzed separately, the N orth
Central Cancer Treatment Group trial 9831 (N9831), and NSABP B-31 (B-31).
Bird B R H , Swain S M Clin Cancer Res 2008;14:14-24
©2008 by American Association for Cancer Research
• NSABP B31– Age
– 2% < 50 yo vs 5.4% > 60 yo– LVEF > 4 AC
– 12% if LVEF < 55%– Concomitant > sequential– Hypertension comedications
• B31/N9831– 6.7% pts who had completed AC had a lower LVEF or
developed cardiac symptoms preventing the initiation of TZT
– 1/3 pts who started TZT discontinued it: 4.7% with symptomatic CHF, 14.2% with confirmed asymptomatic decline in LVEF, and the rest for noncardiac reasons
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• SEER database• 2,028 patients ≥ 66, stage I-III, 2005-2009, trastuzumab
– 71.2% < 76– 71.2% < 76– 66.8% w/o comorbidities (Charlson)– 85.2% w/ chemotherapy– 81.7% w/ complete trastuzumab treatment (> 9 months)– Factors correlated w/ incomplete treatment
• Age 80+ vs 66-70 OR 0.40 (0.30-0.55)• Comorbidities 2 vs 0 OR 0.65 (0.49-0.88)
Vaz-Luiz. J Clin Oncol 2014
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Bevacizumab(Avastin ®)
> 65 yo ≤ 20%
MBC L1
Miller N Engl J Med 2007
> 65 yo ≤ 20%
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ATE eventsChemo only
N = 782
Chemo + beva
N = 963
Global 1.7 3.8
No risk factor 1.0 1.8
ATE and bevacizumab (various cancers)(ATE = arterial thrombo embolism)
No risk factor 1.0 1.8
< 65 yo 1.4 2.1
≥≥≥≥ 65 yo (N = 279) 2.5 7.1
Previous history of ATE 3.4 15.7
≥≥≥≥ 65 yo and previous history 2.2 17.9
Scappaticci. J Natl Cancer Inst 2007
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%< 70
N = 2018
70+
N = 233*
HTN grade ≥ 3 4.2 6.9
Proteinuria grade ≥ 3 1.5 4.0
ATHENA: CT wo /anthracyclines + beva(breast cancer only )
ATE (A or V) 3.3 2.9
Stop for toxicity
ATE
CHF
15
1.8
0.3
23
2.9
0.6
HTN 1.8 2.9
Biganzoli. Annals Oncol 2011
*175 (7.8%) 70+, 51 (2.3%) 75+, 7 (0.3%) 80+
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Signatures ?
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Mammaprint®
295 pts < 53 yo
40 %
15 %
25,000 genes, 78 tumours, 70 genes, 17 pN0, all < 5 5 yo
van’t Veer, Nature 2002; van de Vijver, NEJM 2002
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MINDACT
• 6,600 pts < 70
– FEB 2007-AUG 2011– 11,291 registered pts– 6,673 enrolled (59.1%)
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Radiothérapie
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XRT
• Pathologie faible risque– Schémas hypofractionés– Irradiation partielle accélérée� Amélioration logistique/accès aux soins
• Omission si pT1 ER+ ?– Surtout si > 80A, comorbidités, bonne observance HT
• CALGB 9343 Hughes ASCO 2010 et NEJM 2004
Khan, Semin Radiat Oncol 2012
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Problèmedémographique
Rechercheclinique
peureprésentée
Phénomène hétérogène
Espérance de vie ou
pronostic « hors cancer »
?représentée
Mortalitéspécifique
et effetssecondairessignificatifs
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Competing causes of mortality
Cumulative probability of
death
Cumulative probability of
Breast NHL
Deaths attributed to the primary cancer (solid dots) and those attributed to comorbidity (open circles)
probability of death vs
attained age
CompetingHR of death
Kendal. Cancer 2008
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5 key messages for elderly BC patients
1. Under and over-treament are frequent2. Access to innovation is unbalanced3. Geriatric problems are far more frequent than usually
believed– 2/3 impaired G8, > 50% functional dependence, >10% cognitive
dysfunctions, 20% depression, > 40% significant comorbidities, > dysfunctions, 20% depression, > 40% significant comorbidities, > 50% risk of malnutrition, polypharmacy, etc.
4. ���� Comprehensive Geriatric Assessment CGA– Brings to clinicians new information in > 2/3 cases– Modifies clinical decision in 20-25% cases (function & nutrition)
5. Competing risks for mortality� call for a certain degree of assessment of life
expectancy to balance treatment decision
Caillet. J Clin Oncol 2011; Kenis. Ann Oncol 2013Bode. EBCC9 2014, abstract 414
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Protocol ASTER 70s
GERICO 11 / PACS10
MicroarrayqRT-PCR
CGA
GERICO 11 / PACS10
Adjuvant systemic treatment for oestrogen-receptor (ER)-positive HER2-negative breast carcinoma in women over 70 according to
Genomic Grade (GG): chemotherapy + endocrine treatment versus endocrine treatment. A French UNICANCER Geriatric Oncology Group
(GERICO) and Breast Group (UCBG) multicentre phase III trial
EUDRACT N°2011-004744-22, PHRC national 2011, NCT01 564056
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Toussaint, BMC Genomics 2009
8 genes (4 reporter + 4 reference)9 genes (6 reporter + 3 reference)
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http://www.eprognosis.org/
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4-year mortality score in general elderly populatio n
Health retirement study
• > 50 yo (40% > 70 yo)
− Construction 11,701 subjects
− Validation 8,009 subjects
Lee. JAMA 2006
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R**
1:1
All patients
Cy1+ GCSF
Cy2+ GCSF
Cy3+ GCSF
Cy4+ GCSF
q3w q3w q3w
HT 5 yr
Group I **High GG
Arm B = CT + HT
Arm A = HT HT 5 yrXRT
XRT
baseline 16 weeks 1, 2, 3 & 4 year
MMSE, IADLQLQ C30 & ELD15LVEFSocioeconomicStandard Lab
PolymedicationsMMSE, IADLQLQ C30 & ELD15LVEFSocioeconomicWillingness
G8, CCIPolymedicationsMMSE, IADLQLQ C30 & ELD15LVEFSocioeconomic
Chemo toleranceStandard Lab
Completecurativesurgery
Screening
GERICO 11 (EUDRACT N°2011-004744-22, PHRC national 2011, NCT0 1564056)
1,100
All patientsLee ScoreG8, CCI
Polymedications
Genomic Grade(GG)
evaluation
CCIPolymedications
Events
Group IILow GG
NO CHEMOTHERAPY IS RECOMMENDED - Follow up
1, 2, 3 & 4 year
1 blood + serumWillingnessStandard Lab1 blood + serum
SocioeconomicWillingness
Standard Lab every year
1 blood + serum (M12 & M48)
Events
Screening
** Group I include both high and equivocal GG cases
*Randomization stratified on pN, G8 and centre
time
2,000
900
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August 31st 2014
1391
738
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A frailty revealed… and assessed
• 2006: Mrs BON… IR… 84 yo– No previous medical history (high blood sugar?)– Husband: 86 yo w/ severe advanced Parkinson, 2 children– Breast self exam � T1c N0 M0 left breast– 54 kg/167 cm, BMI 19.4 (<25)
• Conservative surgery + axillary lymph node dissection
+5
+1
+1
• Conservative surgery + axillary lymph node dissection– Invasive ductal carcinoma, 17 mm, SBR II, 8 N-– ER- PgR-, Ki 67 40%, HER2-
• Adjuvant strategy– Chemotherapy with anthracylines (GERICO 06)? + XRT
• Scoring– Oncologist: PS 0 � “Easy! Go for it“– Geriatrician
• Functional status, cognition, nutrition, GDS � OK• However ! 3 falls < 1 year
���� Lee 7 ~ 50% 4-yr mortality
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FEC, AACR, FAC, ASCO, CMF, DXR, PK/PD, CEX, 5FU
CDDP, CalvertAUC, ESMO, ChatelutAUC, CTC, population PK, FOLFIRI, FOLFOX
7, CPA, DFS, DDFS, OS, TTP, NCI, CYP
P450, JCO, JNCI, HER2, PI3K, mTOR, Phase 0, ECCO, ib and
ab…etc.
Charlson, CIRSG, CGA, MNA, GDS, MMS, ADL,
IADL, GFI, CMR2, JAGS, G8, Oncodage, VES-13,
TRFs, JGO, NIA, Walter’s score, Lee’s
score…etc.
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FEC, FAC, ADL, IADL, CMF, DXR, PK/PD, CEX, 5FU CDDP, Calvert and Chatelut AUC, GDS, population PK, FOLFIRI, MMS, FOLFOX, CPA, DFS, OS, TTP, NCI, GERICO, EORTC TFE, JCO, JNCI, Charlson, JGO, CIRSG, EGS, EGA, MNA, GFI, Lee’sscore, JAGS…etc.
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15th SIOG Conference - Prague, Czech Republic
Geriatric oncology and Supportive Care: A global Ap proach to Advance the Science
SAVE THE DATE - 12 to 14 November 2015