1. Metastatic Breast Cancer Elderly Patients Dr Prue Francis Peter MacCallum Cancer Centre Melbourne, Australia

4. Mean age of global population is increasing Figure taken from United Nations World Population Prospects at http://esa.un.org/unpp/index.asp?panel=2 55 50 45 40 35 30 25 20 15 Year United States South Korea Japan China India Mexico Pakistan 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 Median age (years)

5. Elderly Patients Significant Variability in Fitness and Co-morbidities Physically fit and independent     Frail needing substantial functional assistance

7. Life expectancy in senior adults: a large variability reflecting health status variability Top 25th percentile ( FIT seniors) Lowest 25th percentile ( FRAIL seniors) 50th percentile ( MEDIAN life expectancy) Walter LC et al. JAMA 2001, 285, 2750-2756 Health status groups Domains Cognition Comorbidity Emotional conditions Function Geriatric syndromes Nutrition Pharmacy Socioeconomic conditions

8. Metastatic Breast Cancer Goals of Therapy To prolong life and control symptoms while maintaining a good quality of life In elderly important to minimize toxicity and maintain independent function

13. Metastatic Breast Cancer Chemotherapy in Elderly Instead of ..... Consider docetaxel paclitaxel + gemcitabine (GT) weekly nab-paclitaxel/paclitaxel CMF Capecitabine ( < 1000 mg/m 2 po bd) AC, EC, FAC, FEC liposomal or weekly anthracycline CMF oral cyclophosphamide + methotrexate (metronomic CM) vinorelbine + gemcitabine vinorelbine or gemcitabine

15. ANZ 0001 Advanced Breast Cancer 1 st line chemotherapy trial Eligibility: Unsuited to more intensive chemotherapy RANDOMIZE ECOG PS (0-1 v 2-3) liver or brain metastases Intermittent Capecitabine 2000mg/m 2 d1-14 q3w Continuous Capecitabine 1300mg/m 2 d1-21 q3w Classical CMF oral C d1-14, ivMF d1,8 q4w

16. ANZ 0001 Intermittent Capecitabine N=107 % Continuous Capecitabine N=107 % Classical CMF N=109 % Age < 50 9 11 21 50-59 27 36 23 60-69 (median 62 yrs) 41 35 30 70+ 23 18 26 ECOG PS 0-1 88 88 86 2 10 9 12 3 2 3 2 Liver and/or brain metastases 45 48 47 ER+ or PR+ 62 67 64 Adjuvant CMF 19 20 21 AC+CMF 10 9 7 AC 6 5 5 Taxane 2 4 4

17. ANZ 0001 Progression Free Survival Number at risk Combined Capecitabine 214 51 18 8 CMF 109 19 3 1 Median Hazard Ratio (95% CI) 6 0.86 (0.67 - 1.10) 7 1.00 Logrank p-value: 0.2 0 6 12 18 24 30 36 42 48 months from randomization 0 0.2 0.4 0.6 0.8 1 proportion progression-free Capecitabines CMF

18. ANZ 0001 Overall Survival 0 6 12 18 24 30 36 42 48 months from randomization 0 0.2 0.4 0.6 0.8 1 proportion alive Capecitabine CMF Number at risk Combined Capecitabine 214 149 77 31 13 CMF 109 72 29 8 4 Median Hazard Ratios (95% CI) 22 0.72 (0.55 -0 .94) 18 1.00 Logrank p-value: 0.02

19. ANZ 0001 Duration of protocol treatment (%) Capecitabine improved overall survival by being equally active, less toxic and more tolerable than CMF. Stockler et al, J Clin Oncol (online Oct 2011) Intermittent Capecitabine n=107 Continuous Capecitabine n=107 Classical CMF n=109 6 months or less 61 59 79 7 to 11 months 21 24 17 12 or more months 19 17 5

23. Metastatic Breast Cancer Elderly Patients Help elderly patients and their loved ones choose the appropriate pathways