Cancer du sein et sujet âgéCancer du sein et sujet âgé

Docteur Etienne BrainOncologie Médicale

Hôpital René Huguenin / Institut CurieSaint-Cloud, France

etienne.brain@curie.fr

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

… treatment decision process

• LVEF by MUGA scan normal• Not in GERICO 06 trial, but OK for the oncology staff!• The lady “accepted”….

… 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)

Pelike from Attica480–470 BC

Musée du Louvre

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

2009

2050

http://www.un.org/esa/population/publications/ageing/ageing2009chart.pdf

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

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 ?

De Angelis. Lancet Oncol 2013

Relative survival accounts for mortality from causes other than the relevant cancer, which can vary widely between countries

• 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

Phénotype

Plus de formes hormonosensibles (RH+)Moins de formes agressives (triple négatif , HER2+++)Moins de formes agressives (triple négatif , HER2+++)

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

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

Cheang, Clin Cancer Res 2008; Durbecq, CROH 2008

• British Columbia Cancer Agency• 1986-1992• 4,046 pts

• Jules Bordet• 2,723 pts

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

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

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

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)

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)

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

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

Trastuzumab use60-64 yo vs 85+

36% vs 6%p<.001

Moran, EBCC-9, abstract 415

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

Présentation clinique

Freyer Ann Oncol 2006

Les traitements

En pratique…

• 1.009 MBC65-74A 500> 75A 509

• 107 oncologues

Freyer Ann Oncol 2006

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)

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

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

• 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

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

Cancer controlatéralOstéoporose

MyalgiesHyperlipidémie

TAM IA

Cancer controlatéralThrombosesK endomètre

Bouffées de chaleurNeurocognitionFonction sexuelle

HyperlipidémieCardiovasculaire

?

Bouffées de chaleurThromboembolies

K endomètreSignes génitourinaires

Arthralgies/myalgiesOstéoporose

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)

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

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)

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

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

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

La chimiothérapie adjuvante « marche » si on est attentif aux

effets secondaires…effets secondaires…

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

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

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)

… mais principalement si ER - !

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

We may try to avoid the risk of cardiotoxicity induced by

anthracyclines: TC & liposomal doxorubicin

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

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

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%

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

All

DFS OSCALGB / CTSU 49907 (AC or CMF vs X)

ER-

ER+

Muss, NEJM 2009

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: journals.permissions@oup.com.

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: journals.permissions@oup.com.

Green bars: CMFBlue bars: weekly docetaxel

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

Biganzoli, Lancet Oncol 2012

Targeted treatments

Lack of specific data!But clinical evidence for benefit

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

Trastuzumab

> 60 yo ≤≤≤≤ 16%

Piccart NEJM 2005

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

• 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

Bevacizumab(Avastin ®)

> 65 yo ≤ 20%

MBC L1

Miller N Engl J Med 2007

> 65 yo ≤ 20%

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

%< 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+

Signatures ?

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

MINDACT

• 6,600 pts < 70

– FEB 2007-AUG 2011– 11,291 registered pts– 6,673 enrolled (59.1%)

Radiothérapie

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

Problèmedémographique

Rechercheclinique

peureprésentée

Phénomène hétérogène

Espérance de vie ou

pronostic « hors cancer »

?représentée

Mortalitéspécifique

et effetssecondairessignificatifs

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

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

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

Toussaint, BMC Genomics 2009

8 genes (4 reporter + 4 reference)9 genes (6 reporter + 3 reference)

http://www.eprognosis.org/

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

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

August 31st 2014

1391

738

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

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.

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.

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