Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer Cytotoxic Therapy in Metastatic Breast Cancer
Cytotoxic Therapy in Metastatic Breast Cancer 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 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 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 )
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
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
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
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
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 +/-
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 +/-
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!
Triple Negative Metastatic Breast Cancer (TNBC) Chemotherapy as for HER2 neg. pts. ++ Experimental therapies within studies ++ Platinum salts 4 C +/-
Palliative High Dose Chemotherapy High dose-therapy 1a A - - (No treatment outside studies)