Cancer du sein et sujet âgé - Longue Vie et Autonomie · 1 Cancer du sein et sujet âgé Docteur...

1

Cancer du sein et sujet âgé

Docteur Etienne BrainOncologie Médicale

Hôpital René Huguenin / Institut CurieSaint-Cloud, France

[email protected]

• 2006: Mrs BON… IR… 84 yo– Previous history: HBP; high blood sugar?– Fully independent, no depression, feels ”better” than most her

friends– Husband: 86 yo w/ severe advanced Parkinson, 2 children– Breast self exam � T1c N0 M0 left breast– 54 kg (stable)/167 cm, no anorexia, – Treatment: metoprolol, lisinopril, hydrochlorothiazide,

atorvastatine• 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

A frailty revealed…

2

• LVEF by MUGA scan normal

• Not in GERICO 06 trial, but OK for the oncology staff!

• The lady “accepted”….

… treatment decision process

• LVEF by MUGA scan normal

• Not in GERICO 06 trial, but OK for the oncology staff!

• The lady “accepted”….

• 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 2017 i.e. 95 yo)

… treatment decision process & respect

3

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

4

China has the largest elderly population (92 millio n)… but this is only 7% of the Chinese population!!!

www.worldmapper.org

Binder-Foucard INCa report 2013

5

De Angelis Lancet Oncol 2013

Relative survival accounts for mortality from causes other

than the relevant cancer, which can vary widely between

countries

Breast

Ovary

20071991 2002

2013 2015

6

• 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 40-49 1 in 68– Age 50-59 1 in 37– Age 60-69 1 in 26– Ever 1 in 8

Worldwidebreastcancer.com

Current dilemna and extreme positions

1. Therapeutic nihilism– Elderly patients do not receive any treatment

2. The intermediate position?– Elderly patients may benefit from treatments

3. Blind therapeutic enthusiasm– Elderly patients receive futile/non beneficial

treatments

� Place and role of geriatrician and oncologistPelike from Attica 480–470 BC

Musée du Louvre

7

Phénotype

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

BC biology according to age

de Kruijf Mol Oncol 2014, Jenskins Oncologist 2014

8

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 screening > 70?

16

Warner NEJM 2011; Royce JAMA 2014; Gross JAMA 2014

Age(yr)

Nb of trial(s) Relative riskof death (95%CI)

60-69 Malmö &Ostergöland

0.68 (0.54-0.87)

70-79 Ostergöland 1.12 (0.73- 1.72)

75+: YES YOU CAN, but– No mass screening– Depends on life expectancy

9

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

Treated with chemotherapy ifER+ N+ stage I/II breast cancer

Initial treatment for stage II breastcancer by age

SEER database ; 49616 women with stage I/II breast cancer ≥67y

BCS = breast conserving surgery ; XRT = radiotherapy

Undertreatment

Schonberg JCO 2010

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Breast cancer mortality

Other cause mortality

• Univariate HR 1.66 (95% CI 1.34-2.06), p<0.001

• Multivariable HR 1.63(95% CI 1.23-2.16), p<0.001

Cau

sesp

ecifi

cde

ath

Substudy from TEAM trial (adjuvant exemestane)

Age <65y Age ±75yAge 65 – 74y

Schonberg JCO 2010, Van de Water JAMA 2012

Under & overtreatment

Kendal Cancer 2008

Competing causes for mortality

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• A sizeable proportion of elderly with operable breast cancer die of NON-CANCER-related causes

• Absolute benefit of treatments is lower

N = 14048 new early breast cancer, ≥50y, FUP 4,7y

Overtreatment

Ali Br J Cancer 2011

Radiothérapie

12

Hughes J Clin Oncol 2013

After BCS: TAM vs XRT + TAM (CALGB 9343)

334/636 deaths(21 i.e 6.3% due to BC)

Radiotherapy

• Omission if pT1 ER+? (NCCN)– According to life expectancy– > 80 yo, multi-morbidities, good compliance to endocrine treatment?

• Low risk patients– Once-per-week fraction schedule (Whelan regimen)

– Accelerated partial breast irradiation (APBI)• Larger radiation doses given to the localized tumour bed (instead of to the

entire breast)

� Spare extensive and burdensome transportations

But don’t neglect the psychological burden of recurrenc e!

Khan Semin Radiat Oncol 2012

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Les traitements

Le cancer du sein de la femme âgée se prête volontiers à

l’hormonothérapie car il est plus souvent RH+

Mais entre anti-aromatase (letrozole/FEMARA, anastro zole/ARIMIDEX, exemestane/AROMASINE 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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• TAM / 0

15105

60 %

50 %

40 %

30 %

20 %

10 %

rech

ute

26,5

38,3

45,0

24,7

15,1

33,2

contrôle

TAM 5A

• IA / TAM

Réduction du risque de rechute

Bénéfice absolu à 10

ans

RO+ 41 % 13,6 %

Réduction du risque de rechute

Bénéfice absolu à 10

ans

RO+ Post-MP

20 % 5 %

AI 5A

COMPLIANCEis the issue!!!

TAM AINeurocognition

Sexuality

Hot flushes

Thrombosis & embolism

Uterus cancer

Gynecological tractus

Vaginal discharge

Cataract

Arthralgias & myalgias

Osteoporosis

Fractures

Dryness

Cardiovascular

Lipid profile

?

15

Copyright © American Society of Clinical Oncology

Morales, L. et al. J Clin Oncol; 26:3147-3152 2008

Getting a grip on aromatase inhibitor–associated arthr algiasDawn L. Hershman

724 patients � 265 (40%) 65+ � 164 (23%) 70+

Baselga. N Engl J Med 2012Pritchard. Clin Breast Cancer 2013

70+ vs <70Similar efficacy & incidences of AEs

More on-treatment deathsBut

Prior chemo x 2 if <70

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• European phase IIIb• Expanded-access multicenter trial• 2133 patients, 26% 70+• Key AEs: stomatitis, fatigue, anemia, NIP

Jerusalem. Ann Oncol 2016

<70 70+

AE-related treatment discontinuations (%) 13 24

Median duration of exposure (months) 5 4

Dose reduction/interruption (%) 27/54 38/61

Stomatitis any grade/3-4 (%) 52/8 56/12

Asthenia any grade/grade 3-4 (%) 21/3 29/6

Decreased appetite (%) 14 22

Hyperglycemia grade 3-4 (%) 2 5

NIP (%) 9 11

La chimiothérapie, c’est plus compliqué…

Car index thérapeutique plus étroit que l’hormonothéra pie

Des doses généralement ajustées (inférieures)

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Physiological variations x PK & PD

Mechanism Consequences

Absorption

Gastric dumping and secretions �

Absorption of proteins, vitamins and drugs �

Metabolism

Hepatocytes, blood flow, CYP P450 activity �

Interactions (CYP P450)

Protein synthesis, (de-) activation of drugs and 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

34

18

• Myelosuppression : greater in older patients– Lower threshold (<20%) for primary prophylaxis of febrile neutropenia w/ G-CSF

• Cardiomyopathy : more common in older patients– Certainly if underlying cardiac disease

• Mucositis, delayed nausea and vomiting• Peripheral or central neurotoxicity

– Debilitating and interfering w/ functionality and independence– !Concomitant problems that affect mobility and function (e.g. arthritis)

• Renal function : declines with age! ~ 1 mL/min/year – Creatinineserum = insufficient! Cockcroft-Gault CLcreatinine = better but not as

accurate as in younger patients � MDRD/CDK-EPI = best in elderly?

Benefit/risk balance of chemotherapy is narrower than other treatments, especially in elderly

• CPA & renal function

• Capecitabine– 750-1000 mg/m² x 2/d 2 wk/3

Gelman. J Clin Oncol 1984; Crivellari. J Clin Oncol 2 000; Bajetta. J Clin Oncol 2005

CMF

Chemotherapy � Specific doses!!!

19

0

0.2

0.4

Cumulative proportion with event

0.6

0.8

1.0Hazard ratio (>65:£65) = 2.2595% 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

431151

£65*>65*

*Patients at risk

£65

>65

• 630 patients (3 phase III) with 32 CHF26% >550 mg/m²

>50%: reduction of LVEF <30% w/ chemo

Doxorubicine, CHF and age

• HRage

2.25 (1.04–4.86) vs 3.28 (1.4–7.65) if >400 mg/m²

Swain. Cancer 2003

van Dalen. Cochrane Database Syst Rev 2006 & 2008;Aapro. Ann Oncol 2011; Accordino. J Clin Oncol 2014

• Careful assessment• Upper cumulative dose• Close monitoring (US>MUGA)• Less cardiotoxic strategy

– Infusion (≥6 hr vs shorter) HR 0.27 (95%CI 0.09-0.81)– Analogs (epirubicin) HR 0.36 (95%CI 0.12-1.11)– Liposomal formulations HR 0.20-0.38 (95%CI 0.05-0.75)– Iron chelating agent dexrazoxane HR 0.29 (95%CI 0.20-0.44)– Sequential administration if trastuzumab

• Cardiovascular risk reduction interventions– β- and ACE inhibitors

Anthracyclines

20

• 2 cornerstones– Paclitaxel <80 mg/m²qw– Docetaxel q3w but not standard @ 100 mg/m²!

• Same pharmacokinetics , but increased risk of neutropenia ± febrile if 65+– q3w 75 mg/m² grade 3-4 ANC/FN: 63%/16% vs 30%/0%– qw 35 mg/m² > 50% grade ≥ 3 � RD: 26 mg/m²– q2w 50 mg/m² GERICO-04

– Grade 3-4 neurosensory/motor toxicity 28%/14% (vs <18%/<8% if <65)

• Nab-paclitaxel– Efficacy comparable with solvent-based taxanes

– No need for steroid premedication

Taxanes

Del Mastro. Ann Oncol 2005;ten Tije. J Clin Oncol 2005; Girre. Ann Oncol 2008; Biganzoli. Cancer Treat Rev 2016

Oral chemotherapy

PROS CONS

ConvenienceLess need to visit clinic

Reduced complianceFailure to start therapy;

missed doses; overdosage

Greater feeling of control Patient persists takingdrug despite AEs

No difficulty w/ IVadministration

No AE w/ central line

Less cost to health caresystem and/or patient

Patients are lesstied to hospital

Less support frommeeting fellow patients

Rousseau. CROH 2010; Biganzoli. Eur J Cancer 2015

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La chimiothérapie adjuvante « marche » si on est attentif aux

effets secondaires…

DFS

OS

• CALGB (1975-1999)

• 4 randomized trials

• 6487 pts> 65 yo 542 (8%)> 70 yo 159 (2%)

• Results– Benefit identical– Toxicity careful!!

• Toxic deaths 1.5%

Adjuvant chemo for breast cancerAll

All

≤50

≤50

≥65

≥6551-64

51-64

Muss JAMA 2005

22

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 (%)

Pinder J Clin Oncol 2007

ACN =

4,712

OtherchemoN = 3,921

No chemo

N = 34,705

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)

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

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)

Adjuvant chemotherapy and mortality

Adjuvant chemo is useful FIRST

in ER-, pN0 or pN+, even > 70 yo

*: BC specific mortality

Giordano & Elkin J Clin Oncol 2006

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All

ER-

ER+

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

Muss NEJM 2009

GERICO 06 (EUDRACT N° 2005-000069-20, PHRC national 2005)

MC MC MC MC XRT

ADLTolerance

CGAADL + MNA +MMS + GDS +

CIRSG

QLQ-C30Willingness


CIRSG

QLQ-C30WillingnessTolerance


CIRSG

QLQ-C30WillingnessTolerance

1 & 2 yearDFS & OS

ADLTolerance

ADLTolerance

± trastuzumab

if HER2+++

trastuzumabif HER2+

q3w q3w q3w

4 cycles of “AC-like” chemoIn MC, M stands for liposomal non pegylated doxorub icin

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1. Febrile neutropenia 15%2. Risk of denutrition 15% vs 38%3. Impact on QoL (social & role functioning)4. Cardiac tolerance of trastuzumab5. No palmar plantar erythrodysesthesia6. DFS3A 85%

Copyright © American Society of Clinical Oncology

Jones, S. et al. J Clin Oncol; 27:1177-1183 2009

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

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Targeted treatments

Lack of specific data!But clinical evidence for benefit

Tyrosinekinase

domain

Ligand-bindingdomain

Erb-B1EGFRHER1

Erb-B2HER2/neu

Erb-B3HER3

Erb-B4HER4

Trans-membrane

TGF-αEGFEpiregulinBetacellulinHB-EGFAmphiregulin

Heregulin(neuregulin-1)

Heregulin(neuregulin-1)EpiregulinHB-EGFNeuregulins-2,3,4

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

26

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 No rth

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

– 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

27

- 2 gr 3 LVSD (0.5%) (95% CI, 0.1%-1.8%)- 13 significant asymptomatic LVEF decline (3.2%) (95% CI, 1.9%-5.4%)

Tolaney NEJM 2015

- Adjuvant! Online not accurate in older patients- Predict quite accurate for OS prediction

Standard decision tools

de Glas Lancet Oncol 2014 & Br J Cancer 2016

28

General recommendations for adjuvant chemo & tratsuzumab in elderly

• Focus on ER-

• Regimen– Validated 4 AC, 6 CMF– Option 4 TC– Capecitabine no– Docetaxel qw no– Sequential regimen no data– Liposomal doxorubicin ?

• Primary prophylaxis of febrile neutropenia w/ G-CSF

• No restriction on trastuzumab if chemo indicated– 4 TC + trastuzumab– Paclitaxel qw x 12 + trastuzumab– TCH x 6??? (carboplatin AUC 6!)

Miles Breast Cancer Res Treat 2013

Pertuzumab

29

Verma N Engl J Med 2013Dieras J Clin Oncol 2014

Barrios ASCO 2015

T-DM1

Kamilla 194 pts 65-69, 78 pts 70-74, 120 pts 75+

%< 70

N = 2,018

70+

N = 233*

HBP gade ≥ 3 4.2 6.9

Proteinuria grade ≥ 3 1.5 4.0

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

ATHENA: CT w/o anthracyclines + beva

*175 (7.8%) 70+, 51 (2.3%) 75+, 7 (0.3%) 80+

30

Biganzoli, Lancet Oncol 2012

APHINITY

31

80 pts HER2+ MBC≥ 70 Years

(≥65/≥60y with co-morbidity)

Pertuzumab +

Trastuzumab

Pertuzumab + Trastuzumab +metronomic CT

® 1:1 T-DM1

Primary endpointPFS at 6 months of PH or PHM

Pertuzumab 840 mg loading dose, further 420 mg q3w ivTrastuzumab 8 mg/kg loading dose, further 6 mg/kg q3w ivChemotherapy Metronomic chemotherapy: cyclophosphamide 50 mg/d p o continuouslyOn progression Option to have T-DM1 (3.6 mg/kg iv q3w) till progression

PD

Stratification: ER/PgR, previous HER2 treatment, G8Secondary endpointsOS, BCSS, toxicity, RR (RECIST v1.1), HRQoL, evolution of GA during treatment

EORTC 75111-10114(Co-PI Hans Wildiers & Etienne Brain)

32

Problèmedémographique

Rechercheclinique

peureprésentée

Mortalitéspécifique

et effetssecondairessignificatifs

Phénomène hétérogène

Espérance de vie ou

pronostic « hors cancer »

?

Definition of “old” x ageing heterogeneity

Age Top 25 th%Fit

50th%Intermediate

Lowest 25 th%Sick

50 40 33 24.5

70 21.3 15.7 9.5

75 17 11.9 6.8

80 13 8.6 4.6

85 9.6 5.9 2.9

90 6.8 3.9 1.8

95 4.8 2.7 1.1

Women life expectancy

Walter JAMA 2001

33

Multimorbidities across age

Piccirillo, Critical Rev Oncol Haematol 2008

dementia CHF

solid tumour AIDS

diabetes HBP

Kendal Cancer 2008

Competing causes for mortality

34

Do we have tools?

Comprehensive Geriatric Assessment

Assessment Instrument Administration Prognosis

Dependency, functionalstatus

PS, Activity of Daily Living (ADL), Instrumental ADL

Self administered +

ComorbidityCharlson Comorbidity Index (CCI), Cumulative Illness rating Scale-Geriatric (CIRS-G)

Self- or interviewer-administered or chart-based

+

Economic / social support

Life conditions, relatives, care-givers ?

CognitionFolstein Mini-mental State Examination (MMSE)

Interviewer-administered

+functional status

Depression Geriatric Depression Scale (GDS) Self administered +

Polypharmacy List ?

NutritionMini Nutritional Assessment (MNA), BMI

Interviewer-administered

+

Geriatricsyndromes

Dementia, delirium, falls+

functional status

Mobility/falls Timed-up-and-go-test, Tinetti Performance-tests ?

35

≥ 75 yo1st visit

New cancer or relapse

G8Physician± nurse

≤ 14/17> 14/17

Primary focus on*: systemic treatment?

Decision 1

YESNO

Standard health caresvigilance and geriatrician

sought according to needs

GA

* But not exclusively

Adjusted health cares± MDTB 2 and decision 2Geriatric interventions

1. Streamlining geriatrician time2. Involvement of oncologists3. Impact- Decisions 1 and 2- Geriatric interventions- Day hospital in geriatric oncology

MDTB 1 + geriatrician

Adapted recommendations for patient’s referral for GA at Instit ut Curie

MDTB: multi disciplinary tumor board


friends– Husband: 86 yo w/ severe advanced Parkinson, 2 children– Breast self exam � T1c N0 M0 left breast– 54 kg (stable)/167 cm, no anorexia, – Treatment: metoprolol, lisinopril, hydrochlorothiazide,




• Scoring– Oncologist: PS 0 � “Easy! Go for it“– Geriatrician


A frailty revealed…

36


friends– Husband: 86 yo w/ severe advanced Parkinson, 2 children– Breast self exam � T1c N0 M0 left breast– 54 kg (stable)/167 cm, no anorexia, BMI 19.4 (<25, 18.5-21)– Treatment: metoprolol, lisinopril, hydrochlorothiazide,




• Scoring– Oncologist: PS 0 � “Easy! Go for it“ !!!– Geriatrician


A frailty revealed… and assessed+5

+1+1 +2+2+2

+3+2+1

+1

+0

� Lee 7 ~ 50%� G8 = 13

6 key messages forelderly cancer patients

1. Age and standard approach upfront influence treatment decision in

40% cases but not always in the right direction!

2. Under and over-treament are frequent

3. Access to innovation is unbalanced

4. Geriatric problems are far more frequent than usually believed

– 2/3 impaired G8, > 50% functional dependence, >10% cognitive

dysfunctions, 20% depression, > 40% significant comorbidities, > 50%

risk of malnutrition, polypharmacy, etc.

5. � Comprehensive Geriatric Assessment CGA

– Brings to clinicians new information in > 2/3 cases

– Modifies clinical decision in 20-25% cases (function & nutrition)

6. Competing risks for mortality � call for a certain degree of assessment

of life expectancy to balance treatment decision

� need for specific researchCaillet J Clin Oncol 2011; Kenis Ann Oncol 2013; Bode EBCC9 2014, abstract 414

38

Agent Name Approval N Age ≥ 65 N Age ≥ 75

Palbociclib 2/201537 44% 8 10%86 25% --

Everolimus 7/2012 290 40% 109 15%Pertuzumab 6/2012 60 15% 5 1%Eribulin mesylate 11/2010 121 15% 17 2%

Lapatinib 1/201034 17% 2 1%

282 44% 77 12%

Ixabepilone 10/200745 10% 3 <1%32 13% 6 2.5%

Package Insert, “Geriatric Usage” section

Few older adults included in registration studies!Breast cancer as an example

Courtesy to Arti Hurria (adapted)

GERICO ≥ 2,000 patients2002 Creation (F Pein & AC Braud) Age Phase Primary endpoint N Ancillary Publication

2002 G-01: X+VNR PO breast, lung, prostate 70+ II ADL 80 PK CROH 2010

G-02: CT XELOX CCR M+ 70+ II ADL 60 PK JGO 2011

2004 G-03: per op brachyXRT breast < 3 cm pN0 70+ IIFaisabilité

Qualité40 Cost Brachy 2013

2005 G-04: CT TxT q2w breast M+ 70+ II IADL 27/60 NA Poster

G-05: CT TxT q2w NSCLC M+ 70+ II IADL 5/60 NA Poster

2006 G-06: CT adjuvant anthra (MC) breast ER- 70+ II ADL 40 Will CROH 2010

2008 G-07: validation CRASH 70+ Cohorte Composite NA NA NA

Sarcoma Aegide + G-CSF 70+ II R Composite NA NA NA

2009 G-09: breast M+ HER2+++ X + lapatinib 70+ II Composite 4/52 NA Poster

Retrospective L1 CT M+ breast (Bergonié) 75+ Cohorte Description 500 NA CROH 2001

DOGMES L1 DXR lipos (GINECO) 70+ II RR 60 NA EJC 2012

2010 G-10/GETUG P-03: CT TxT prostate + PK 75+ II R Composite 66/60 :144 PK Poster

PRODIGE 20 (G-08): CT ± beva CCR M+ 75+ IIR/III Composite 102 CTC/RX Pending

2011 ASTER 70s/G-11/PACS 10 : CT adj breastRH+ HER2- GGI

70+ IIIOS

(competing risks)897/1,080

1,671/2,000BiomarkersCost, Will

Poster, oral

2012 ELAN (PAIR ORL, GORTEC/GERICO) 70+ Multiple OS 380 NA Poster

SHS (cognition, acceptability, etc.) 70+ SHS Qualitative res NA Poster

2013 Frail lung (GFPC/GERICO), poly vs mono 70+ III OS + QoL 252 NA NA

2014UCGI-30 (G-12) XRT/CTneo vs XRT rectumOSAGE (Besançon)

75+IIII/II

R0 + IADLMTD, RR EOT

42054

2014 Pain (intergroupe soins support AFSOS) 70+ Cohorte Description > 1,000

2015 ASTER 2/3 + EORTC/BIG 70+ III Outcome + QoL 1,200/2,500

39

Protocol ASTER 70sGERICO 11 / PACS10

Adjuvant systemic treatment for oestrogen-receptor ( ER)-positive HER2-negative breast carcinoma in women ov er 70

according to Genomic Grade (GG): chemotherapy + end ocrine treatment versus endocrine treatment. A French UNIC ANCER

Geriatric Oncology Group (GERICO) and Breast Group (UCBG) multicentre phase III trial

MicroarrayqRT-PCR

CGA

EUDRACT N° 2011-004744-22, PHRC national 2011, NCT01564056

R**

1:1

All patientsLee ScoreG8, CCI

Polymedications

Genomic Grade(GG)

evaluation

CCIPolymedications

Events

Group IILow GG

NO CHEMOTHERAPY IS RECOMMENDED - Follow up

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

1, 2, 3 & 4 year

MMSE, IADLQLQ C30 & ELD15LVEFSocioeconomicStandard Lab

1 blood + serum

PolymedicationsMMSE, IADLQLQ C30 & ELD15LVEFSocioeconomicWillingnessStandard Lab1 blood + serum

G8, CCIPolymedicationsMMSE, IADLQLQ C30 & ELD15LVEFSocioeconomicWillingness

Standard Lab every year

1 blood + serum (M12 & M48)

Events

Chemo toleranceStandard Lab

Completecurativesurgery

Screening

** Group I include both high and equivocal GG cases

*Randomization stratified on pN, G8 and centre

time

GERICO 11 (EUDRACT N° 2011-004744-22, PHRC national 2011, NCT0 1564056)

2,000

1,100

900

Hypothesis B > A ∆+7.5% (A 80% vs B 87.5%) HR 0.60 α 5% β 10%

40

Inclusions on May 19 th, 2016(FR + BE) (48 months)

1,989

1,089

41

• Young patient

– Social and family obligations

(children)

– Quantity of life +++

• Elderly patient

– QoL+++

– Independence

– Staying at home

• Oncology

– Therapies and innovation

– Toxicity, response, survival

• RECIST

• NCI CTC v4.0

• Survival (DFS, PFS, DDFS,

OS)

– Fast-moving world

– "Molecular portrait" of

tumour & GEP

• Geriatrics

– Symptoms, diagnosis

– Quality of survival, i.e. amount of life with good QoL

• Cognition

• Functional status

• QoL

• Nutrition, etc.

– Requiring time

– "Global portrait" of patient & CGA

CGA

versus

or

+

?

Two worlds confronting

one another?

Genomic

defect

targeted

therapy

CGA

defect

targeted

geriatric

intervention

FEC, AACR, FAC, ASCO, anti-PDL1,

anti-PD1, CMF, SABCS, PD-1, PDL1,

DXR, PK/PD, CEX, 5FU CDDP, Calvert

AUC, ESMO, Chatelut AUC, CTC, TILs,

population PK, EORTC, FOLFIRI,

ctDNA, FOLFOX 7, CPA, DFS, CALGB,

DDFS, OS, TTP, NCI, CYP P450, JCO,

JNCI, HER2, PI3K, mTOR, Phase 0,

ECCO, ib and ab, Unicancer, EORTC,

SWOG, CALGB, etc.

Charlson, CIRSG, CGA, AD, MCI,

MNA, GDS, MMS, ADL, IADL,

GFI, CMR2, JAGS, EUGMS, G8,

CARG, Oncodage, VES-13, TRFs,

JGO, NIA, SoFOG, Walter’s score,

Lee’s score, CRASH, etc.

42

FEC, FAC, SoFOG, ADL, IADL, CMF,

SABCS, DXR, PK/PD, CEX, G8, EORTC,

5FU CDDP, MCI, Calvert and Chatelut

AUC, CARG, GDS, population PK, AD,

FOLFIRI, MMS, FOLFOX, CPA, CRASH,

SWOG, DFS, OS, TTP, NCI, GERICO,

TILs, CARG, anti-PDL1, anti-PD1,

EORTC TFE, JCO, JNCI, Charlson, JGO,

CIRSG, PD-1, PDL-1, ctDNA, EGS, EGA,

MNA, GFI, Unicancer, Lee’s score,

JAGS, etc.

To be practice changing,

let us be practice sharing!

Join our unique CME accredited training programme lead by international experts in the field ofgeriatrics AND oncology designed to provide specific skills in assessment, care pathways andtherapeutic choices about the elderly patients with cancer in order to provide the basis of theassessment and the multi-dimensional approach that should be applied to elderly cancerpatients.

Admission process opens on January 9, 2017

Find out more at www.siog.org

This course is an ESO recommended activity and is held with the support of

Pending auspices and endorsements:

Course director: Silvio Monfardini (IT) Course co-director: Etienne Brain (FR) Course coordinator: Giuseppe Colloca (IT)

43

www.siog.org

Cancer du sein et sujet âgé - Longue Vie et Autonomie · 1 Cancer du sein et sujet âgé Docteur...

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Transcript of Cancer du sein et sujet âgé - Longue Vie et Autonomie · 1 Cancer du sein et sujet âgé Docteur...