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Impact on autonomy of biweekly docetaxel as first-line chemotherapy (CT) regimen in elderly patients with metastatic breast cancer (MBC) – A FNCLCC Gerico Group Phase II multicentre trial
9th SIOG Meeting, October 16–18, 2008, Montreal, Canada: Posters high risk for the TN subtype. We have shown that this risk persists until age 70. We have also shown that AA women over 70 are more likely to have the ER+/PR+/HER2- subtype, the subtype with the best survival, while this variation is not seen in white women. We reconfirm that Hispanic women under 45 have an increased risk for the TN subtype. We have demonstrated that the association of age with breast cancer subtypes varies with race/ethnicity, and may reflect lifestyle and/or biologic differences. Breast cancer is not a homogeneous disease. To deliver the best and most efficacious therapy, age and race/ethnicity are important to consider when breast cancer subtypes are discussed. P.50 Activity and safety of trastuzumab in advanced breast cancer in elderly women (70 years) in italy S. Monfardini1 *, A. Brunello1 , D. Crivellari2 , F. Puglisi3 , A. Paccagnella4 , A. Molino5 , G. Mustacchi6 , M. Beda7 , A. Luciani8 , E. Simoncini9 , C. Pogliani10 , U. Basso1 . 1 Istituto Oncologico Veneto – I.O.V. – Padova; 2 CRO-Aviano; 3 University Hospital of Udine; 4 Medical Oncology Department of Mestre-Venezia; 5 Division of Medical Oncology, University of Verona; 6 Medical Oncology Division, Trieste; 7 Oncology Division, Camposampiero Hospital; 8 San Paolo Hospital, Milan; 9 Division of Medical Oncology, Brescia; 10 Hospital of Saronno, Italy Background: Despite the high prevalence of breast cancer (BC) in elderly pts, no specific trial of activity and safety of Trastuzumab (T) has addressed pts older than 70 years with HER2-positive disease, and the only available data are taken from subgroup analyses. Methods: Charts of pts 70 with inoperable locally advanced/metastatic BC over expressing HER2 treated with chemotherapy (CHT) and T in 10 Italian Centers were reviewed. Primary endpoints were Response Rate (RR), Time to Progression (TTP), toxicity and cardiac events. Results: Fifty-six pts were eligible, median age 74 years (range 70−92). ECOG PS range was 0−2. Twenty-eight pts (50%) were ER negative. 43 pts (76%) had G2-G3 tumors. Cardiovascular risk factors are reported in Table 1. Taxane-based regimens were used in 28 pts (50%), Vinorelbine-based in 23 pts (41%) and Trastuzumab monotherapy in 5 pts (9%). Basal LVEF was 64% (range 50−78%). A multidimensional geriatric assessment had been done in 22 pts. Partial or complete response was obtained in 32 pts out of 46 evaluable (RR= 69%). Other 12 pts had disease stabilization (21%). No difference in RR was seen among subgroups (Taxane vs Vinorelbine; age <80 vs 80 years; previously treated vs chemonaive pts; high vs low grade), yet a trend for increased response for pts with ER negative disease was observed (78 vs 58%, p = 0.08). Median TTP was 8.7 months at a median follow-up of 14 months. Toxicity did not correlate with CHT regimen or age. A reduction of LVEF >10% but <20% was observed in 3 out of 38 (8%) pts for whom serial echocardiograms were available. After a median of 11.5 months of treatment, two hypertensive crises, an episode of chest pain and an episode of atrial fibrillation occurred in 4 pts, the latter leading to treatment discontinuation. Conclusions: RR and TTP for elderly pts receiving CHT plus T appeared to be comparable to published data. Taxanes and Vinorelbine seem to have comparable activity and toxicity in this age class. Periodical assessment of cardiac safety is therefore strongly recommended in this category of pts due to the frequent concomitant cardiovascular comorbidity. Table 1: Cardiovascular risk factors (other than hypertension alone)
Previous anthracyclines Diabetes, obesity, hyperlipemia, hypertension Smoking Cardiac arrythmias Deep vein thrombosis Ischemic cardiopathy Cor pulmonale
# pts
%
22 11 7 4 3 2 1
39 20 12 7 5 4 2
S45 P.51 Impact on autonomy of biweekly docetaxel as first-line chemotherapy (CT) regimen in elderly patients with metastatic breast cancer (MBC) – A FNCLCC Gerico Group Phase II multicentre trial V. Girre1 *, F. Rousseau2 , E. Blot3 , S. Gourgou-Bourgade4 , F. Gouttenoire5 , J. Geneve5 , S. Delaloge6 . 1 Institut Curie, Paris, 2 Institut Paoli Calmettes, Marseille, 3 Centre Henri Becquerel, Rouen, 4 Centre Val d’Aurelle, Montpellier, 5 F´ed´eration Nationale des Centres de Lutte Contre le cancer, Paris, 6 Institut Gustave Roussy, Villejuif, France Purpose of the study: Besides quality of life and symptom palliation, the maintenance of autonomy appears as a major concern in elderly patients undergoing chemotherapy. Data regarding consequences on activities/instrumental activities of daily living (ADL/IADL) of taxane-based CT regimens for localized/advanced breast cancer are sparse. The main objective of this study dedicated to elderly women with first-line MBC was to assess the impact of a biweekly docetaxel regimen – expected to be associated with better tolerance profile than weekly or 3-weekly scheduleson autonomy, investigating instrumental activities of daily living (IADL) during and after treatment. Summarized description of the project: Women were eligible if they were >70 years, had measurable MBC not previously treated by CT for metastases, together with standard satisfactory haematological, renal and liver functions and scores of autonomy (IADL or ADL 4). After written informed consent, they were scheduled to receive up to 6 monthly cycles (Cy) of docetaxel biweekly (50 mg/m2 ). IADL and ADL scores were evaluated every second cycles, together with GDS (Geriatric Depression scale) and tumour assessment (RECIST criteria). Results: 27 pts were included between 05/2005 and 07/2006. Baseline characteristics were: median age 76 (70–86), PS0 48% and PS1 52%, median IADL and ADL scores 8 (4.5–8) and 6 (5.5–6), respectively, HRpositive 52.2%, and 54% had bone, 46% lung, 44% liver involvement. Prior adjuvant CT and hormone therapy were 30% and 48%, respectively. A total of 117 cycles were administered with a median delay of 14 days between two infusions. Median treatment duration was 3 months. The trial was stopped prematurely due to 2 toxic deaths both related to pulmonary events: one patient developed acute interstitial lung toxicity attributed to docetaxel and one developed an infection involving pneumocystis carinii. Significant grade 3−4 toxicities encountered on-treatment are shown below. At 2 months, 18% of pts had decrease in IADL, 9% in ADL, and 44% in geriatric depression scores. Among 26 evaluable pts, there were 4% CR, 23% PR (ORR 27%). Disease control rate was 41%, while 27% had progressive disease. Grade 3–4 toxicities
% Cy
% pts
Neutropenia Nail changes Febrile neutropenia Dyspnea Diarrhea Mucositis
14% 3% 0% 3% 1% 1%
27% 12% 0% 12% 4% 4%
Conclusions: Despite interesting disease control and low objective toxicities rates, especially on autonomy parameters, docetaxel biweekly was associated with unexpected fatal events precluding its routine use in elderly pts.
Previous anthracyclines Diabetes, obesity, hyperlipemia, hypertension Smoking Cardiac arrythmias Deep vein thrombosis Ischemic cardiopathy Cor pulmonale
# pts
%
22 11 7 4 3 2 1
39 20 12 7 5 4 2
S45 P.51 Impact on autonomy of biweekly docetaxel as first-line chemotherapy (CT) regimen in elderly patients with metastatic breast cancer (MBC) – A FNCLCC Gerico Group Phase II multicentre trial V. Girre1 *, F. Rousseau2 , E. Blot3 , S. Gourgou-Bourgade4 , F. Gouttenoire5 , J. Geneve5 , S. Delaloge6 . 1 Institut Curie, Paris, 2 Institut Paoli Calmettes, Marseille, 3 Centre Henri Becquerel, Rouen, 4 Centre Val d’Aurelle, Montpellier, 5 F´ed´eration Nationale des Centres de Lutte Contre le cancer, Paris, 6 Institut Gustave Roussy, Villejuif, France Purpose of the study: Besides quality of life and symptom palliation, the maintenance of autonomy appears as a major concern in elderly patients undergoing chemotherapy. Data regarding consequences on activities/instrumental activities of daily living (ADL/IADL) of taxane-based CT regimens for localized/advanced breast cancer are sparse. The main objective of this study dedicated to elderly women with first-line MBC was to assess the impact of a biweekly docetaxel regimen – expected to be associated with better tolerance profile than weekly or 3-weekly scheduleson autonomy, investigating instrumental activities of daily living (IADL) during and after treatment. Summarized description of the project: Women were eligible if they were >70 years, had measurable MBC not previously treated by CT for metastases, together with standard satisfactory haematological, renal and liver functions and scores of autonomy (IADL or ADL 4). After written informed consent, they were scheduled to receive up to 6 monthly cycles (Cy) of docetaxel biweekly (50 mg/m2 ). IADL and ADL scores were evaluated every second cycles, together with GDS (Geriatric Depression scale) and tumour assessment (RECIST criteria). Results: 27 pts were included between 05/2005 and 07/2006. Baseline characteristics were: median age 76 (70–86), PS0 48% and PS1 52%, median IADL and ADL scores 8 (4.5–8) and 6 (5.5–6), respectively, HRpositive 52.2%, and 54% had bone, 46% lung, 44% liver involvement. Prior adjuvant CT and hormone therapy were 30% and 48%, respectively. A total of 117 cycles were administered with a median delay of 14 days between two infusions. Median treatment duration was 3 months. The trial was stopped prematurely due to 2 toxic deaths both related to pulmonary events: one patient developed acute interstitial lung toxicity attributed to docetaxel and one developed an infection involving pneumocystis carinii. Significant grade 3−4 toxicities encountered on-treatment are shown below. At 2 months, 18% of pts had decrease in IADL, 9% in ADL, and 44% in geriatric depression scores. Among 26 evaluable pts, there were 4% CR, 23% PR (ORR 27%). Disease control rate was 41%, while 27% had progressive disease. Grade 3–4 toxicities
% Cy
% pts
Neutropenia Nail changes Febrile neutropenia Dyspnea Diarrhea Mucositis
14% 3% 0% 3% 1% 1%
27% 12% 0% 12% 4% 4%
Conclusions: Despite interesting disease control and low objective toxicities rates, especially on autonomy parameters, docetaxel biweekly was associated with unexpected fatal events precluding its routine use in elderly pts.