Cytotoxic Therapy in Metastatic Breast Cancer

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1 Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer Cytotoxic Therapy in Metastatic Breast Cancer

2 Cytotoxic Therapy in Metastatic Breast Cancer Version 2002: von Minckwitz Versions : Dall / Fersis / Friedrichs / Harbeck / von Minckwitz / Möbus / Schneeweiss / Stickeler / Untch Version 2012: Harbeck / Möbus

3 Cytotoxic Therapy Disease-Free and Overall Survival 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

4 Treatment of Metastatic Breast Cancer Predictive Factors Therapy Factor Endocrine therapy receptor status (primary tumor, metastasis) 1a A ++ previous response 2b B ++ Chemotherapy previous response 1b A ++ Trastuzumab HER2 (primary tumor, better metastasis) 1a A ++ Bisphosphonates bone metastasis 1a A ++ (other biological factors see chapter predictive factors )

5 Cytotoxic Therapy Goals Oxford LoE: 1b 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: 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

6 Cytotoxic Therapy LoE: 1c 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

7 Cytotoxic Therapy Duration LoE GR 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 - Stop therapy in case of 1c A ++ Progression Non-manageable toxicity

8 Cytotoxic Therapy Drug Selection AGO: ++ The choice of cytotoxic drugs to be used depends on: Aggressiveness of disease and localization of metastases Previous treatments Combination with biologicals Tumor biology Health condition and age Patients expectations

9 Cytotoxic Therapy 1 st -Line Therapy Monotherapy: Doxorubicin, epirubicin, mitoxanthrone (A), liposomal doxorubicin (A lip ) 1b A ++ Docetaxel (q3w), paclitaxel (q1w) (T) 1b A ++ Nab-paclitaxel 2b B + Vinorelbine 3b B + Capecitabine 2b B + Polychemotherapy: A + T 1b A ++ Paclitaxel + Capecitabine 2b a B + Docetaxel + Capecitabine after adj. A 1b A + T + Gemcitabine after adj. A 2b B ++ (F) + A + C or A lip + C 1b B ++ CMF(1+8) 2b B +/- BMF (bendamustine) 1b B +/-

10 Cytotoxic Palliative Therapy after Anthracycline Treatment 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 +/-

11 Cytotoxic Therapy after Previous Taxane and Anthracycline Treatment Experimental therapies within studies ++ Capecitabine 2b B ++ Eribulin 1b B ++ Vinorelbine 2b B ++ (Peg)-liposomal Doxorubicin 2b B + Gemcitabine + Cisplatin / Carboplatin 2b B +/- Gemcitabine + Capecitabine 2b B +/- Gemcitabine + Vinorelbine* 2b B +/- Ixabepilone + Capecitabine* 1b B - *Cave neutropenia / therapeutic index!

12 Triple Negative Metastatic Breast Cancer (TNBC) Chemotherapy as for HER2 neg. pts. ++ Experimental therapies within studies ++ Platinum salts 4 C +/-

13 Palliative High Dose Chemotherapy High dose-therapy 1a A - - (No treatment outside studies)

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