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
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
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 non-
hematological toxicities (ie, loss of appetite, severe fatigue,
and mucositis)
• The incidence of treatment-related deaths increased
linearly with advancing patient age (P.0022)
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+
Muss et al. J Clin Oncol 2007
26
Loibl et al. Brest Cancer Res 2008
Older women experienced more febrile neutropenia (8% vs 4%)Primary prophylaxis with G-CSF not allowed
25
TC was superior in older patients as well as in younger women
Romond et al. JCO 2012; Perez et al. JCO 2008; Sutter et al. St Gallen 2007; Russel et al. JCO 2010
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)
Age >50 Post-AC LVEF
Adapted from Biganzoli et al. Crit Rev Oncol Hematol 2009
1
Focusing on elderly patients…
Adapted from Biganzoli et al. Crit Rev Oncol Hematol 2009
Weekly docetaxel and paclitaxel in elderly patients: safety data
• 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
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
2
1
3
4
Nab-paclitaxel
• Solvent-free paclitaxel; no need for premedication; at
least as effective as standard taxanes
The Breast 2011
The Breast 2011
till disease progression or toxicity
nab-paclitaxel 125 mg/m2
day 1, 8, 15 q 28
nab-paclitaxel 100mg/m2
day 1, 8, 15 q 28
R
Stratification factors:age 65-74 vs ≥ 75 yrs; diabetes yes, no G3-4 CIRS yes, no IADL deficient yes, no
• Age ≥ 65;
• Advanced HER2-neg breast cancer*
• No prior CT for advanced breast cancer*HER2- positive but considered not eligible for anti-HER2 therapy
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)
Nab-paclitaxel 100 mg/m2
days 1, 8, 15 q 28 x4Epirubicin 30 mg/m2
days 1, 8, 15 q 28 x 4
R
• 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 Recommendations1)
• 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
Conclusions
1Biganzoli et al. Lancet Oncol 2012
• 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
Conclusions (I)
Back up
Nab-paclitaxel
plus
capecitabine x 6
Adjuvant setting
• 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])
Age ≥ 65 yearsStage 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
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
AC x 4
or
CMF x 6R
N=100 N=107
A B