Cytotoxic Therapy in Metastatic Breast Cancer

Diagnosis and Treatment of Patients
with Primary and Metastatic Breast Cancer
© AGO
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1
Cytotoxic Therapy in
Metastatic Breast Cancer
Cytotoxic Therapy in
Metastatic Breast Cancer
© AGO
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.

Guidelines Breast
Version 2012.1

www.ago-online.de

Version 2002:
von Minckwitz
Versions 2003–2011:
Dall / Fersis / Friedrichs / Harbeck / von
Minckwitz / Möbus / Schneeweiss /
Stickeler / Untch
Version 2012:
Harbeck / Möbus
Cytotoxic Therapy
Disease-Free and Overall Survival
© AGO
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Oxford / AGO
LoE / GR
Guidelines Breast
Version 2012.1

www.ago-online.de

A survival benefit has been shown
in recent single prospective
randomized studies
1b
An increase in survival during time in
clinical studies has been shown in
retrospective analyses
2a
Treatment of Metastatic Breast Cancer
Predictive Factors
© AGO
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1
Therapy
Factor
Oxford / AGO
LoE / GR
Endocrine
therapy
receptor status
(primary tumor, metastasis)
previous response
1a
2b
A
B
++
++
Chemotherapy
previous response
1b
A
++
Trastuzumab
HER2
(primary tumor,
better metastasis)
1a
A
++
bone metastasis
1a
A
++
www.ago-online.de
Bisphosphonates
(other biological factors see chapter „predictive factors“)
Cytotoxic Therapy
Goals
© AGO
Oxford LoE: 1b
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1
GR: A
AGO: ++
Mono-chemotherapy:


Favourable therapeutic index
Indicated in case of


Slow, not life-threatening progression
Insensitive to or progression during endocrine therapy
Poly-chemotherapy:


www.ago-online.de
Unfavourable therapeutic index
Indicated to achieve rapid remission in the case of



Extensive symptoms
Imminent life-threatening metastases
Survival benefit in comparison to sequential singleagent therapies with the same compounds not proven
Therapeutic index evaluates overall efficacy, toxicity and impact on quality of life
Cytotoxic Therapy
© AGO
LoE: 1c
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1
www.ago-online.de
GR: A
AGO: ++

Evaluate compliance before therapy (especially
in elderly patients, with reduced PS, or
significant co-morbidities)

Assess subjective and objective toxicities,
symptoms and PS repeatedly

Use dosages according to published protocols

Assess tumor burden at baseline and approx.
every 2 months, i.e. every 2-3 cycles
Cytotoxic Therapy
Duration
© AGO
Oxford / AGO
LoE GR
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1
As long as therapeutic index remains positive
 Treatment until best response
2b B
 Treatment until progression
2b B
 Change to alternative regimen
before progression
2b B
+
+
-
www.ago-online.de

Stop therapy in case of


Progression
Non-manageable toxicity
1c A
++
Cytotoxic Therapy
Drug Selection
© AGO
AGO: ++
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1
The choice of cytotoxic drugs to be used depends on:
www.ago-online.de

Aggressiveness of disease and localization of metastases

Previous treatments

Combination with biologicals

Tumor biology

Health condition and age

Patients expectations
Cytotoxic Therapy
1st-Line Therapy
© AGO
Oxford / AGO
LoE / GR
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1
Monotherapy:





Doxorubicin, epirubicin, mitoxanthrone (A),
liposomal doxorubicin (Alip)
Docetaxel (q3w), paclitaxel (q1w) (T)
Nab-paclitaxel
Vinorelbine
Capecitabine
1b
1b
2b
3b
2b
A
A
B
B
B
++
++
+
+
+
1b
2ba
1b
2b
1b
2b
1b
A
B
A
B
B
B
B
++
+
+
++
++
+/+/-
Polychemotherapy:

www.ago-online.de






A+T
Paclitaxel + Capecitabine
Docetaxel + Capecitabine after adj. A
T + Gemcitabine after adj. A
(F) + A + C or Alip + C
CMF(1+8)
BMF (bendamustine)
Cytotoxic Palliative Therapy
after Anthracycline Treatment
© AGO
e. V.
Oxford / AGO
LoE / GR
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1
www.ago-online.de

Docetaxel q3w
1a
A
++

Paclitaxel q1w
1a
A
++

Capecitabine
2b
B
++

Nab-paclitaxel
2b
B
++

Peg-liposomal doxorubicin
2b
B
+

Vinorelbine
2b
B
+

Docetaxel + Peg-liposomal Doxo
1b
B
+/-

Etoposid / cisplatinum
2b
B
+/-
Cytotoxic Therapy after Previous
Taxane and Anthracycline Treatment
© AGO
Oxford / AGO
LoE / GR
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1






www.ago-online.de



Experimental therapies within studies
Capecitabine
Eribulin
Vinorelbine
(Peg)-liposomal Doxorubicin
Gemcitabine + Cisplatin / Carboplatin
Gemcitabine + Capecitabine
Gemcitabine + Vinorelbine*
Ixabepilone + Capecitabine*
*Cave neutropenia / therapeutic index!
2b
1b
2b
2b
2b
2b
2b
1b
B
B
B
B
B
B
B
B
++
++
++
++
+
+/+/+/-
Triple Negative Metastatic
Breast Cancer (TNBC)
© AGO
e. V.
Oxford / AGO
LoE / GR
in der DGGG e.V.
sowie
in der DKG e.V.
Guidelines Breast
Version 2012.1
Chemotherapy as for HER2 neg. pts.
www.ago-online.de
++

Experimental therapies within studies

Platinum salts
4
++
C
+/-
Palliative High Dose Chemotherapy
© AGO
e. V.
in der DGGG e.V.
sowie
in der DKG e.V.
Oxford / AGO
LoE / GR
Guidelines Breast
Version 2012.1

High dose-therapy
(No treatment outside studies)
www.ago-online.de
1a A
--