MULTIDISCIPLINARY MANAGEMENT OF METASTATIC DISEASE SYSTEMIC THERAPY F. Cardoso, MD Jules Bordet...
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Transcript of MULTIDISCIPLINARY MANAGEMENT OF METASTATIC DISEASE SYSTEMIC THERAPY F. Cardoso, MD Jules Bordet...
MULTIDISCIPLINARY MANAGEMENT OF MULTIDISCIPLINARY MANAGEMENT OF METASTATIC DISEASEMETASTATIC DISEASE
SYSTEMIC THERAPYSYSTEMIC THERAPY
F. Cardoso, MDF. Cardoso, MDJules Bordet Institute, Brussels, BelgiumJules Bordet Institute, Brussels, Belgium
BELGIAN BREAST MEETING 2008
October 4-5, 2008
Breast Cancer
Despite ↑ incidence - ↓ mortality
* Screening & early diagnosis
* Education & advocacy
but also
* Better treatment options
* Better treatment strategies
BUT
The evolution as been quite different between adjuvant and metastatic settings
WHY?
Different diseases?
Different biology?
Different aims
Different attitude of physicians?
Advances in EARLY BC are measured in YEARS (DECADES)
Cohort by year of dxTotal n=2152
1991-92
(1)
1994-55
(2)
1997-98
(3)
1999-01
(4)
Median
survival days
438 450 564 667
p value Cohort 1+2 vs 3 (0.002) Cohort 3 vs 4 (0.04)
Chia et al ASCO 2003 Population Based Study in British Columbia
Advances in METASTATIC BC are measured in DAYS – MONTHS(max: few years; median survival MBC= 2-3 yrs)
Are MBC guidelines needed? definitely YES
RISK OF RECURRENCE REMAINS PRESENT THROUGHOUT ALL PATIENTS’ LIFETIME
Saphner T et al. J Clin Oncol 1996; 14: 2738–2746.
Recurrence rate/year (%)
0 1 2 3 4 5 6 7 8 9 10
0
2
4
6
8
10
12
14
16
Time (years)
Node-negative
Node-positive
Are MBC guidelines needed? definitely YES
EBCC-ESO METASTATIC BREAST CANCER GUIDELINES
First step: 12 Recommendations Statements Published: The Breast 16, 9–10, 2007
1st Session: EBCC-4 (Nice, March 2006):
“Are MBC guidelines possible?” - YES
Preparatory work: Task Force created; meetings; some decisions:
1. MBC guidelines cannot be rigid 2. Should be built on principles and not on specific treatment
regimens3. Need to be in line with latest research findings (biology…)
The management of MBC is complex; therefore involvement of all appropriate specialities in a multi/interdisciplinary team (medical, radiation, surgical and imaging oncologists, palliative care, psycho-social, among others) is crucial.
1ST STATEMENT
12 RECOMMENDATIONS STATEMENTS
2nd STATEMENT
From first diagnosis of MBC, patients should be offered personalised appropriate psychosocial, supportive and symptom-related interventions as a routine part of their care.
MAIN ISSUES IN MBC MANAGEMENTMAIN ISSUES IN MBC MANAGEMENT
• Confirmation of diagnosis Confirmation of diagnosis
• Definition of main goal of treatmentDefinition of main goal of treatment
• Available therapiesAvailable therapies
• Factors determining the choice of treatmentFactors determining the choice of treatment
• Special subgroups (Endocrine-responsive, HER-2+, Special subgroups (Endocrine-responsive, HER-2+, basal-like)basal-like)
• New agentsNew agents
• Individualizing treatmentIndividualizing treatment
PATIENT PREFERENCES
Psychosocial, supportive and
palliative interventions
2nd STATEMENT
3rd STATEMENT
HER-2 seems to be quite consistent between P and M sites:In our series, only 6% discordance by IHC & 7% by FISH (most discordant cases showed greater HER-2 overexpression in M)
However: Conflicting results exist &Interlaboratory variability for both IHC and FISH is a big problem
For all other markers, including Hormonal receptors, the consistency levels are lower
CONFIRMATION OF DIAGNOSIS CONFIRMATION OF DIAGNOSIS
WHENEVER POSSIBLE A BIOPSY OF THE METASTATIC LESION SHOULD BE PERFORMED
DEFINITION OF MAIN GOALS OF TREATMENTDEFINITION OF MAIN GOALS OF TREATMENT
CRUCIAL: Identify the small but very important subset of MBC patients can achieve complete
remission and a long survival – ISOLATED MET
FOR ALL OTHERS
MBC is incurableThe main treatment goal is PALLIATION, transform it
into a chronic diseaseIncrease survival, if possible
Maintain/improve QoLSymptom control
Test new agents/approaches before adjuvant setting
3rd & 4th STATEMENTS
ANY STEM CELL CAN SEED MORE
• Primary cancer must be controlled
• Metastatic foci must be controlled
HOWEVER
We must continue to strive to do better … and keep cure a goal for the future…
Adapted from W Wood, EBCC-6, 2008
• There are few proven standards of care in MBC management
• Well-designed, independent, prospective randomised trials are a priority
• Every proposed option must have a sound scientific rationale, preferably evidence-based
MAIN MESSAGES
AVAILABLE SYSTEMIC THERAPIESAVAILABLE SYSTEMIC THERAPIES
10th STATEMENT
FACTORS to consider in TREATMENT SELECTION
• DISEASE FREE INTERVALDISEASE FREE INTERVAL• PREVIOUS THERAPIES & PREVIOUS THERAPIES &
RESPONSERESPONSE• BIOLOGICAL FACTORS (HR, BIOLOGICAL FACTORS (HR,
HER-2)HER-2)• TUMOR BURDEN (number & TUMOR BURDEN (number &
site of mets)site of mets)• NEED FOR RAPID NEED FOR RAPID
DISEASE/SYMPTOM CONTROLDISEASE/SYMPTOM CONTROL
• BIOLOGICAL AGEBIOLOGICAL AGE• MENOPAUSAL STATUSMENOPAUSAL STATUS• CO-MORBIDITIESCO-MORBIDITIES• P.S.P.S.• SOCIO-ECONOMIC & SOCIO-ECONOMIC &
PSYCHOLOGICAL FACTORSPSYCHOLOGICAL FACTORS• PATIENT’S PREFERENCESPATIENT’S PREFERENCES
From the disease
From the patient
6th STATEMENT
AVAILABLE SYSTEMIC THERAPIESAVAILABLE SYSTEMIC THERAPIES
ADVANCED BREAST CANCERADVANCED BREAST CANCER
Available therapiesAvailable therapies
• ENDOCRINE vs. CHEMOTHERAPY
• COMBINATION vs. SEQUENTIAL SINGLE AGENTS
• WHICH DRUGS? WHICH SCHEDULES?
• MAINTENANCE THERAPY
• WHEN TO STOP
MAIN QUESTIONS / CONTROVERSIES
Endocrine therapy is the preferred option for hormonal receptor positive disease, unless there is concern or proof of endocrine resistance.
The optimal first-line hormonal treatment for postmenopausal patients is an aromatase inhibitor; however tamoxifen remains a viable option.
For pre-menopausal women, tamoxifen combined with ovarian suppression/ablation is the first choice except for tamoxifen resistant tumours.
Optimal post-aromatase inhibitor treatment is uncertain. Maintenance hormonal treatment after chemotherapy is not established but is reasonable.
Concomitant chemo + endocrine therapy should be discouraged.
12 RECOMMENDATIONS7th STATEMENT
LOW RISK GROUPLOW RISK GROUPHR-positiveHR-positive
ENDOCRINE THERAPYENDOCRINE THERAPY+/-+/-
BIOLOGICAL AGENT BIOLOGICAL AGENT
ADVANCED BREAST CANCERADVANCED BREAST CANCER
Available therapiesAvailable therapies
HER-2 negativeHER-2 negative HER-2 positiveHER-2 positiveNo threatening diseaseNo threatening disease
ENDOCRINE THERAPYENDOCRINE THERAPY+/-+/-
HERCEPTIN HERCEPTIN (Tandem trial; others ongoing)(Tandem trial; others ongoing)
ENDOCRINE TREATMENT STRATEGIES IN ADVANCED ENDOCRINE TREATMENT STRATEGIES IN ADVANCED BREAST CANCERBREAST CANCER
19701970 19801980 19901990 20002000
TamoxifenTamoxifen TamoxifenTamoxifen
Megestrol acetateMegestrol acetateAminoglute-Aminoglute-thimidethimide
33rdrd generation AI generation AI
Exemestane/Exemestane/Megestrol acetateMegestrol acetate
33rdrd generation AI generation AI
Faslodex® or SermFaslodex® or Sermor non cross- or non cross- resistant AIresistant AI
Megestrol acetateMegestrol acetate
II
IIII
II
IIII
IIIIII
II
IIII
IIIIII
« Level-1 » evidence-based « Level-1 » evidence-based
EstrogensEstrogensEstrogensEstrogens EstrogensEstrogens
AIAI
Post AIPost AI Much uncertainty persists ! Much uncertainty persists ! Adapted from M. Piccart
Prior AI therapyPrior AI therapy
Fulvestrant LD* + 250 mg / month
+ placebo for exemestane
(n=330)
Fulvestrant LD* + 250 mg / month
+ placebo for exemestane
(n=330)
Exemestane 25 mg po od
+ placebo for
fulvestrant (n=330)
Exemestane 25 mg po od
+ placebo for
fulvestrant (n=330)
*LD, loading dose (500*LD, loading dose (500 mg dmg day ay 1 + 250 mg day 14)1 + 250 mg day 14)
ENDPOINTSENDPOINTS• primaryprimary TTPTTP• secondarysecondary OR rateOR rate duration of duration of
responseresponse CB rateCB rate survivalsurvival quality of lifequality of life
pharmacokineticspharmacokinetics safetysafety
ELIGIBILITYELIGIBILITY• histological histological
confirmationconfirmation• postmenopausal postmenopausal
statusstatus• progression progression
following AIfollowing AI• ER+ and / or PgR+ER+ and / or PgR+• measurable diseasemeasurable disease• performance statusperformance status
0–20–2
ROLE OF FASLODEXROLE OF FASLODEX
ROLE OF FASLODEXROLE OF FASLODEX
EFECT TRIALEFECT TRIAL
TTP (ITT): Kaplan-Meier PlotP
rop
ort
ion
Pat
ien
ts P
rog
ress
ion
-Fre
e
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 3 6 9 12 15 18 21 24 27
3.73.7Median (months)
HR = 0.963, 95% CI(0.819, 1.133), p = 0.6531
Cox analysis, p = 0.7021
ExemestaneFulvestrant
FulvestrantExemestane
MonthsAt Risk:Fulvestrant 351 195 96 50 25 12 4 2 Exemestane 342 190 98 41 21 12 8 6
Pro
po
rtio
n P
atie
nts
Res
po
nd
ing
MonthsAt Risk:Fulvestrant 20 20 16 11 8 3 0 0 Exemestane 18 18 15 10 5 4 3 3
FulvestrantExemestane
9.813.5Median (months)
ExemestaneFulvestrant
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 3 6 9 12 15 18 21 24 27
DURATION OF RESPONSE (from randomisation)
p21rasp21ras
Raf
Nucleus
Mek
ERERERER
Histone acetylation
ER-dependent growth
ERERERER
p38 MAPKp38 MAPK
AIB1AIB1 CBPCBP
Membrane
c-jun c-fos
MAPK
PP
P
P
CROSS-TALK BETWEEN THE ER CROSS-TALK BETWEEN THE ER AND THE GF PATHWAYS AND THE GF PATHWAYS
HER2 EGFr
EREREREREE22
ERERERERTamTam
PI3KPTENPTEN
Cell proliferation
AkTAkT
BADBAD FKHRFKHRGSK-3GSK-3 mTORmTOR
SURVIVALSURVIVAL
Cell proliferation
FasLFasL
N-CORN-COR
Failure of mTOR inhibition to improve the activity of Failure of mTOR inhibition to improve the activity of lezotrole in advanced breast cancer lezotrole in advanced breast cancer
Results of a phase III trial in 992 patientsResults of a phase III trial in 992 patients
SABCS 06, abst. 6091
Median PFS (mo) (95% ci)
CR + PR (%)
Stable disease (≥ 24 weeks)
Clinical benefit (%)
PD as best response (%)
Temsirolimus + lezotroleN = 493
Lezotrole + placeboN = 499
9.2 (7.2 – 11.1) 9.2 (7.4 – 11.1)
24 24
16
40
14
19
43
18
HOW TO IMPROVE TREATMENT OF LUMINAL BC???
LOW RISK GROUPLOW RISK GROUPHR-positiveHR-positive
ENDOCRINE THERAPYENDOCRINE THERAPY+/-+/-
BIOLOGICAL AGENT BIOLOGICAL AGENT
ADVANCED BREAST CANCERADVANCED BREAST CANCER
Available therapiesAvailable therapies
HER-2 negativeHER-2 negative HER-2 positiveHER-2 positiveNo threatening diseaseNo threatening disease
ENDOCRINE THERAPYENDOCRINE THERAPY+/-+/-
HERCEPTIN HERCEPTIN (Tandem trial; others ongoing)(Tandem trial; others ongoing)
TANDEM STUDY: Randomized trial of ANASTROZOLE TANDEM STUDY: Randomized trial of ANASTROZOLE ± ± TRASTUZUMAB in advanced HER2+, HR+ breast cancerTRASTUZUMAB in advanced HER2+, HR+ breast cancer
N=207Median age 55 yearsVisceral disease 1/3
Prior chemo 1/2
Anastrozole
Cross-over 70%
6,8% Response rate 20,3%2,4m Median P.F.S. 4,8m p 0.0016
23,9m Median O.S. 28,5m
32,1m Median O.S. 41,9mif no liver mets p 0.03
Mackey et al., SABC 06, abst. 03
Anastrozole+
Trastuzumab
Trastuzumab added to anastrozole RR, PFS (and possibly OS if no liver mets) IMPORTANCE OF STARTING BIOLOGICAL AGENT SOONAdapted from M. Piccart
ADVANCED BREAST CANCERADVANCED BREAST CANCER
Available therapiesAvailable therapies
• ENDOCRINE vs. CHEMOTHERAPY• WHICH DRUGS? WHICH SCHEDULES?• COMBINATION vs. SEQUENTIAL SINGLE AGENTS• MAINTENANCE THERAPY• WHEN TO STOP
MAIN QUESTIONS
12 RECOMMENDATIONS
The choice between sequential use of single cytotoxic drugs and combination chemotherapy should be taken after consideration of the factors mentioned in paragraph 6, with greatest emphasis on the need for a rapid and significant response and quality of life.
For the majority of patients, overall survival outcomes from sequential use of single cytotoxic drugs are equivalent to combination chemotherapy.
Duration of each regimen and number of regimens should be tailored to each individual patient.
9th STATEMENT
Docetaxel vs. Docetaxel vs. Docetaxel + CapecitabineDocetaxel + Capecitabine
PHASE III TRIAL DOCETAXEL VS DOCETAXEL + CAPECITABINE IN MBC PTS FAILING ANTHRACYCLINES
O’Shaughnessy J et al. J Clin Oncol 2002;20:2812–23
DocetaxelCapecitabine +
docetaxel
n 256 255
L1/L2 (%) 31/53 35/48
Anthracyclines (%) 100 100
ORR (%) 30 42
TTP (months) 4.2 6.1
OS (months) 11.5 14.5
Phase III Registration Trial Planned Interim Analysis
Endpoint GT T p-value
Ind ORR 45.5% 25.5% <0.00005(95% C.I.) (38.5, 52.4) (19.2, 31.8)
Median TTP 5.2 2.9 <0.0001(95% C.I.) (4.2, 8.6) (2.6, 3.7)
Median OS, mos 18.5 15.8(95% C.I.) (16.5, 21.2) (14.4, 17.4)
Paclitaxel vs. Paclitaxel vs. Paclitaxel + GemcitabinePaclitaxel + Gemcitabine
COMBINATION vs. SEQUENTIAL SINGLE AGENTSCOMBINATION vs. SEQUENTIAL SINGLE AGENTS
NO OR MINIMAL CROSSOVER
BUTSubsequent Chemotherapy
PG vs. PDocetaxel 10.5% 10.3%Gemcitabine 3.8% 14.1%
T vs. TCCapecitabine 17 % Docetaxel 20 %
BENEFIT OF COMBINATION IS ONLY LEVEL-2 EVIDENCE-BASEDBENEFIT OF COMBINATION IS ONLY LEVEL-2 EVIDENCE-BASED
• Discuss with patients; new treatment option…• Consider combination in « high risk » fit patients
PACLITAXEL VERSUS DOXORUBICIN VERSUS BOTHPACLITAXEL VERSUS DOXORUBICIN VERSUS BOTHCROSSOVER PART OF TRIAL DESIGNCROSSOVER PART OF TRIAL DESIGN
AA TT ATAT
3434
6.26.2
1414
20.120.1
3333
5.95.9
20 20
22.222.2
4646
8.08.0
--
22.422.4
p valuep value
SS
SS
SS
NSNS
RR%-1st lineRR%-1st line
MEDIAN TTF, mosMEDIAN TTF, mos
MEDIAN OS, mosMEDIAN OS, mos
RR% - 2nd lineRR% - 2nd line
QOLQOL Different toxicities, similar tolerabilityDifferent toxicities, similar tolerability
Sledge, ASCO ‘ 97Sledge, ASCO ‘ 97
739 MBC pts
>Toxicity>Impact on daily life
No or very small gain in survivalUses up “all weapons” faster
COMBINATIONCOMBINATION
>RRFaster symptom/disease control
SEQUENTIAL SINGLE AGENTSSEQUENTIAL SINGLE AGENTS
<ToxicitySimilar survival
Better overall QoLBetter management of resources
<RRSlower symptom/disease control
ESO-EBCC MBC RECOMMENDATIONS
Sequential use of single cytotoxic drugs should be the preferred choice except if:
rapidly progressing diseaselife threatening visceral metastasesneed for rapid disease/symptom control
9th STATEMENT –
2008 Proposal
Define the subgroup of pts who need first line combination because we will not be able to rescue the; with 2nd or 3rd line CT
ADVANCED BREAST CANCERADVANCED BREAST CANCER
MAIN ISSUESMAIN ISSUES
• Confirmation of diagnosis Confirmation of diagnosis
• Definition of main goal of treatmentDefinition of main goal of treatment
• Available therapiesAvailable therapies
• Factors determining the choice of treatmentFactors determining the choice of treatment
• SPECIAL SUBGROUPSSPECIAL SUBGROUPS (Endocrine-responsive, (Endocrine-responsive, HER-2+,HER-2+, basal-like) basal-like)
• New agentsNew agents
• Individualizing treatmentIndividualizing treatment
PATIENT PREFERENCES
Psychosocial, supportive and
palliative interventions
12 RECOMMENDATIONS8th STATEMENT
Trastuzumab should be offered EARLY to ALL HER-2-positive MBC patients, after failure of endocrine therapy if this is appropriate.
Trastuzumab in combination with endocrine therapy is under evaluation in clinical trials and can not yet be considered as standard.
Currently, the optimal management of patients progressing on trastuzumab is uncertain and active research is ongoing in this area.
PIVOTAL PHASE III TRASTUZUMAB COMBINATION TRIAL PIVOTAL PHASE III TRASTUZUMAB COMBINATION TRIAL OVERALL SURVIVAL IN HER2 3+ PATIENTSOVERALL SURVIVAL IN HER2 3+ PATIENTS
Smith IE. Anticancer Drugs 2001;12:S3–10
1.0
0.8
0.6
0.4
0.2
00 5 10 15 20 25 30 35 4045 50
18 25
Time (months)
Prob
abili
ty o
f sur
viva
l
40%
H + P
P
Longer OS: 25.1 vs. 20.3 ms Longer OS: 25.1 vs. 20.3 ms (p=0.046)(p=0.046)
Longer TTPLonger TTP: 7.4 vs. 4.6 ms (p: 7.4 vs. 4.6 ms (p0.001)0.001)
Higher RRHigher RR: 50 vs. 32% (p: 50 vs. 32% (p0.001)0.001)
Longer durationLonger duration: 9.1 vs. 6.1 ms (p: 9.1 vs. 6.1 ms (p0.001)0.001)
H + CT KEY MESSAGES
OPTIMAL USE OF OPTIMAL USE OF TRASTUZUMABTRASTUZUMABIMPORTANCE OF EARLY ADMINISTRATIONIMPORTANCE OF EARLY ADMINISTRATION
1.0
0.8
0.6
0.4
0.2
0
Estim
ated
pro
babi
lity
0 3 6 9 12 15 18 21 24 27 30Months
15.3 27.721.9
Herceptin® + docetaxel (n=92)Docetaxel alone/crossover (n=41) Docetaxel alone (n=53)
M77001 trial: estimated M77001 trial: estimated survivalsurvival
OPTIMAL DURATION OF TRASTUZUMAB TREATMENTOPTIMAL DURATION OF TRASTUZUMAB TREATMENT
– Response rate (48.0 vs. 27.0%; p=0.01)– Clinical benefit rate (75.3 vs 54%; p=0.007)– Time to progression (8.2 vs 5.6 mos; p=0.03)– Overall survival (25.5 vs 20.4 mos; non sign. trend)– No increase in toxicity
Study Design of GBG 26
X: X: Capecitabine 2500 mg/m² d 1 – 14 q 22
R
XH: Capecitabine 2500 mg/m² d 1 – 14 q 22
and continuation of Trastuzumab 6 mg/kg q22
156 pts (from 482 pts needed) recruited between 01/04
- 05/07 ; Recruitment stopped after FDA registration of
lapatinib on advice of IDMC
RESULTS OF THE BIG-GBG TBP
&
Bulk of retrospective data
PUTTING INTO PERSPECTIVE
• Adds to the bulk of existing retrospective data (eg Hermine study)
• The only randomised trial that reached reasonable accrual…
• No safety issues
BUT… LANDSCAPE IS CHANGING: New anti-HER2 drugs
• When to continue trastuzumab with another CT regimen vs. changing to another anti-HER-2 therapy (i.e. Lapatinib)?
• Which are the pts that benefit from continuing trastuzumab vs. shifting to another anti-HER-2 drug vs. shifting to a combination strategy
• MAIN MESSAGE: the HER-2 pathway should continue to be blocked in HER-2 + pts even after progression (for how long?)
THE FUTURE THE FUTURE • NEW AGENTS
• “NEW-OLD AGENTS” (i.e. Capecitabine, liposomal anthracyclines, new taxanes…)
• NEW BIOLOGICAL AGENTS (i.e. Lapatinib, Sunitinib, Bevacizumab…)
• COMBINATION OF “STANDARD” + BIOLOGICAL AGENTS
• COMBINATION OF BIOLOGICAL AGENTS
• BIOMARKERS (Treatment tailoring)
MBC – SYSTEMIC THERAPIESMBC – SYSTEMIC THERAPIES
ADVANCED BREAST CANCER TREATMENTADVANCED BREAST CANCER TREATMENTStill an art…but with GUIDENCEStill an art…but with GUIDENCE
STANDARDS STANDARDS OF CAREOF CARE
TREATMENT TREATMENT TAILORING TAILORING
(BIOLOGICAL (BIOLOGICAL MARKERS)MARKERS)
PATIENT’SPATIENT’SPREFERENCESPREFERENCES
MULTI-DISCIPLINARY TEAM (medical, radiation, surgical and imaging oncologists, palliative
care, psycho-social)
Appropriate PSYCHOSOCIAL, SUPPORTIVE and PALLIATIVE
interventions essential part of routine care
QUALITY OF LIFE ASSESSMENTS
PREVIOUS PREVIOUS THERAPIES, THERAPIES,
OTHER OTHER FACTORSFACTORS
NEW AGENTSNEW AGENTS
RATIONAL USE RATIONAL USE OF AVAILABLE OF AVAILABLE
AGENTS & AGENTS & RESOURCESRESOURCES
KNOWING WHEN KNOWING WHEN TO STOP!!TO STOP!!
CLINICAL CLINICAL TRIALSTRIALS
It matters not how long we live, but how.
“Festus”, Philip James Bailey
BACK-UP
TREATMENT OF WOMEN WITH ADVANCED BREAST CANCERTREATMENT OF WOMEN WITH ADVANCED BREAST CANCERTAKE-HOME MESSAGES - 1TAKE-HOME MESSAGES - 1
• Management of MBC is Management of MBC is complexcomplex; ; multi-disciplinary teammulti-disciplinary team essential essential
• From diagnosis, offer pts appropriate psychosocial, supportive From diagnosis, offer pts appropriate psychosocial, supportive and palliative interventions as a routine part of their careand palliative interventions as a routine part of their care
• PatientsPatients should be invited & encouraged to actively should be invited & encouraged to actively participateparticipate in in all decision-makingall decision-making
• Few Standards of care; ENTER PTS IN WELL-DESIGNED TRIALSFew Standards of care; ENTER PTS IN WELL-DESIGNED TRIALS
• Main therapy goal: PALLIATION (except Main therapy goal: PALLIATION (except small subsetsmall subset who can who can achieve achieve CR & long survivalCR & long survival; treat aggressively); treat aggressively)
• Treatment choiceTreatment choice must take into account several pt- & disease- must take into account several pt- & disease-associated associated factorsfactors (i.e. DFI, previous Rx, ps, HER, HER-2, etc…) (i.e. DFI, previous Rx, ps, HER, HER-2, etc…)
• Hormonal therapyHormonal therapy is the preferred option for HR + MBC, unless is the preferred option for HR + MBC, unless there is concern or prove of endocrine resistance there is concern or prove of endocrine resistance
• Maintenance hormonal treatmentMaintenance hormonal treatment after CT is not established but is after CT is not established but is reasonablereasonable
• HER-2 positive MBCHER-2 positive MBC is a separate disease and should be treated is a separate disease and should be treated accordingly; probably the same for accordingly; probably the same for basal-like BCbasal-like BC
• For the majority of patients, OS outcomes from sequential use of For the majority of patients, OS outcomes from sequential use of single agents are equivalent to combination CTsingle agents are equivalent to combination CT
NEED: New agents but also rational use of available agents (TREATMENT TAILORING – Biological markers)
TREATMENT OF WOMEN WITH ADVANCED BREAST CANCERTREATMENT OF WOMEN WITH ADVANCED BREAST CANCERTAKE-HOME MESSAGES - 2TAKE-HOME MESSAGES - 2
CONFIRMATION OF DIAGNOSIS CONFIRMATION OF DIAGNOSIS
• Is the metastatic lesion representative of the primary tumor?
• Does the biology of the cancer changes during the metastasis process?
• Are HR, HER-2 & other markers concordant between primary and metastatic sites?
SHOULD A BIOPSY OF THE METASTATIC LESION BE MANDATORY?
RISK EVALUATION IN MBCRISK EVALUATION IN MBC
YesYes Hormone receptorsHormone receptors NoNo
> 2 years> 2 years Disease-free intervalDisease-free interval < 2 years< 2 years
limitedlimited No. of metastasesNo. of metastases extensiveextensive
soft tissue, bonesoft tissue, bone Sites of metastasesSites of metastases visceraviscera
NoNo Vital organ involvementVital organ involvement YesYes
RISK EVALUATIONRISK EVALUATION
LOWLOW MODERATE, HIGHMODERATE, HIGH