SIOG Guidelines Update 2014: Use of Taxanes in Older Breast Cancer Patients Laura Biganzoli Medical Oncology Dept New Hospital of Prato Istituto Toscano Tumori Italy
Fundamental steps Task Force (TF) on Use of Taxanes in Older Breast Cancer Patients First meeting: 26th October in Copenhagen, during the SIOG 2013 Annual Conference Several drafts..(thanks to Rob Stepney, medical writer) Last draft circulated to all the members of the TF on September 2014 document still to be finalized Writing Committee Matti Aapro - Clinique de Genolier, Genolier, Switzerland Laura Biganzoli - New Hospital of Prato, Istituto Toscano Tumori, Prato, Italy Tadeusz Pienkowski - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology,Warsaw Poland Sibylle Loibl - German Breast Group, Neu-Isenburg; and Sana-Klinikum Offenbach, Germany Hans Wildiers - CSIR, KU Leuven, Belgium
Rationale & aims Taxanes are key agents in the treatment of breast cancer both in the neo/adjuvant and metastatic setting Review available data on the use of docetaxel, paclitaxel and nab-paclitaxel in elderly breast cancer patients Expert recommendations (position paper)
There is no significant data to support dose modification of docetaxel and paclitaxel based on age alone
Taxanes in early breast cancer In sequence with anthracyclines in the neo/adjuvant setting ie. (F)AC->T In anthracycline-free regimens in low-risk patients ie. TC F, 5-fluorouracil; A, anthracycline; T, taxane; TC, docetaxel plus cyclophosphamyde
26 N =4 adjuvant/neoadjuvant German studies antracycline/taxane based Age groups (< 60, 60 to 64, 64+) Higher rates of dose delays and reductions, hospitalization, therapy discontinuation, hematological toxicity, and some nonhematological toxicities (ie, loss of appetite, severe fatigue, and mucositis) Loibl et al. Brest Cancer Res 2008 CALGB 8541: three different dose schedule of CAF; CALGB 9344: AC +/- paclitaxel; CALGB 9741: AC paclitaxel q 3 vs 2 wks Age in Years at Enrollment: <50, 51-64, 65+ The incidence of treatment-related deaths increased linearly with advancing patient age (P.0022) Muss et al. J Clin Oncol 2007
25 TC was superior in older patients as well as in younger women Older women experienced more febrile neutropenia (8% vs 4%) Primary prophylaxis with G-CSF not allowed
Potential risk factors for CHF/cardiac events in adjuvant Trastuzumab trials NSABP B31* NCTG N9831 HERA ACREC Age 50+ Hypertension medic. Baseline LVEF (<55%) Post-AC LVEF Age 60+ Hypertension medic. Baseline LVEF (<55%) Baseline LVEF (<65%) High BMI (>25) Romond et al. JCO 2012; Perez et al. JCO 2008; Sutter et al. St Gallen 2007; Russel et al. JCO 2010 Age >50 Post-AC LVEF
1 Adapted from Biganzoli et al. Crit Rev Oncol Hematol 2009
Focusing on elderly patients Weekly docetaxel and paclitaxel in elderly patients: safety data 1 2 3 4 Adapted from Biganzoli et al. Crit Rev Oncol Hematol 2009 1 Hainsworth et al. Cancer 2000; 2 Perez et al. Breast Cancer Res Treat 2002, 3 ten Tije et al. Eur J Cancer 2004; 4 Del Mastro et al: Ann Oncol 2005 Efficay was age indepedent Grade 3 leucopenia,granulocytopenia, anorexia, bilirubin elevation and neurotoxicity increased linearly with age Patients over 65 years receiving second-line therapy had the shortest time to neurotoxicity (35% at 6 cycles) Ann Oncol 2011
Nab-paclitaxel Solvent-free paclitaxel; no need for premedication; at least as effective as standard taxanes The Breast 2011
The Breast 2011
Age 65; Advanced HER2-neg breast cancer* No prior CT for advanced breast cancer R *HER2- positive but considered not eligible for anti-her2 therapy nab-paclitaxel 125 mg/m2 day 1, 8, 15 q 28 Stratification factors: age 65-74 vs 75 yrs; diabetes yes, no G3-4 CIRS yes, no IADL deficient yes, no till disease progression or toxicity nab-paclitaxel 100mg/m2 day 1, 8, 15 q 28 Primary endpoint: Event-free survival (event= progressive disease or death without progression or decrease in function defined as loss of >= 1 ADL or IADL from baseline considered by the investigator to be treatment related and confirmed at the subsequent cycle)
R Epirubicin 30 mg/m2 days 1, 8, 15 q 28 x 4 Nab-paclitaxel 100 mg/m2 days 1, 8, 15 q 28 x4
Conclusions In the adjuvant setting taxanes are associated with increased toxicity compared with younger women, but can be added to anthracyclines in high-risk healthy elderly patients, or replace anthracyclines to reduce the cardiac risk (SIOG and Eusoma Recommendations 1 ) In HER-2 positive patients, the combination of docetaxel plus cyclophosphamide offers an alternative to anthracycline-taxane based chemotherapy and reduces the risk of trastuzumab-related cardiac toxicity 1 Biganzoli et al. Lancet Oncol 2012
Conclusions (I) Weekly taxanes are a reasonable option for the treatment of older patients with advanced breast cancer Close monitoring of side effects is recommended since fatigue (docetaxel) and neurotoxicity (paclitaxel) might have a negative impact on function Nab-paclitaxel represents a potential alternative to standard taxanes due to a favorable safety profile (when the 100-125 mg/m2 weekly dose-schedule is used) and shorter time to resolution of sensory neuropathy to a lesser grade without the the need for steroid premedication Studies are ongoing to define the role of nab paclitaxel in older patients
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Adjuvant setting Age 65 years Stage pt3/4 or pn2/3 or stage pt1/2 and pn0/1 (0-3 involved lymph nodes) with an increased risk according to the clinico-pathological or upa/pai-1 criteria AC x 4 or CMF x 6 A B R N=100 N=107 Nab-paclitaxel plus capecitabine x 6 Interim safety analysis after 207 patients completed treatment Treatment A better tolerated than nab-paclitaxel plus capecitabine (treatment discontinuation for AEs 6.6 vs 34.7%). More G 3-4 non-hematological AEs in arm B (59% vs 19%) At 48 months, rates of invasive disease-free survival equivalent between the treatments(hazard ratio [HR] 0.98, [P =.9597]) nab-paclitaxel 100 mg/m2 on days 1, 8, 15 q22 with a week of rest every 6 weeks in combination with capecitabine 2000 mg/m2, days 1-14 orally, divided into 2 daily doses every 3 weeks for 6 cycles