ABC1 - P. Francis - Elderly patients

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ABC1 - P. Francis - Elderly patients

  1. 1. Metastatic Breast Cancer Elderly Patients Dr Prue Francis Peter MacCallum Cancer Centre Melbourne, Australia
  2. 2. Conflict of Interest <ul><li>Support from Roche, Amgen, GSK, Sanofi-aventis </li></ul><ul><li>Acknowledgement </li></ul><ul><li>Matti Aapro </li></ul>
  3. 3. Breast Cancer and Age <ul><li>~ 40% breast cancer diagnosed > 65 years </li></ul><ul><li>~ 20% breast cancer diagnosed > 75 years </li></ul><ul><li>Mean age of population is rising </li></ul><ul><li>Older women under-represented in breast cancer trials </li></ul>
  4. 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. 5. Elderly Patients Significant Variability in Fitness and Co-morbidities Physically fit and independent     Frail needing substantial functional assistance
  6. 6. Elderly Patients Comprehensive Geriatric Assessment <ul><li>Assess comorbidities and functional status </li></ul><ul><li>Provides extra information beyond ECOG Performance Status </li></ul><ul><li>Assists in prediction of treatment toxicity </li></ul><ul><li>Estimation of life expectancy and prognosis </li></ul><ul><li>A </li></ul>
  7. 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. 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
  9. 9. Metastatic Breast Cancer in Elderly Choice of Initial Treatment <ul><li>If ER+ve usually start with endocrine therapy unless life-threatening disease </li></ul><ul><li>Consider multiple lines of hormonal treatment in endocrine-responsive disease (AI, tamoxifen, fulvestrant, non-cross resistant AI, progestin) </li></ul><ul><li>Low dose estrogen therapy maybe effective after clinical benefit on aromatase inhibitor </li></ul><ul><li>Dental check and renal function before bisphosphonate (if bone metastases). Denosumab newer option </li></ul>
  10. 10. Metastatic Breast Cancer in Elderly Hormone Withdrawal <ul><li>Trial of 1 st line Tamoxifen vs CMF in elderly, 23% had disease control following tamoxifen withdrawal - benefit correlated with prior hormone response * </li></ul><ul><li>Also phase II data on clinical benefit after withdrawl of AI - 52% stable at 6 mths # </li></ul><ul><li>Hormone withdrawal - an underutilized non-toxic Rx ? </li></ul>* Taylor et al, Ann Int Med 1986 # Cigler, ASCO 2011, abstract # 559
  11. 11. Metastatic Breast Cancer Chemotherapy in Elderly <ul><li>older patients should not be excluded from receiving chemotherapy </li></ul><ul><li>consider in ER-ve or hormone-refractory disease </li></ul><ul><li>favour monotherapy over combinations </li></ul><ul><li>choose drugs/schedules with safer profiles </li></ul><ul><li>avoid excessive toxicity </li></ul><ul><li>minimize risk of febrile neutropenia </li></ul>
  12. 12. Chemotherapy Drugs in Elderly Consider Baseline Issues <ul><li>Cardiac problems (anthracyclines, trastuzumab) </li></ul><ul><li>Neuropathy (taxanes, vinorelbine) </li></ul><ul><li>Drug interactions (warfarin- capecitabine, lapatinib- digoxin) </li></ul><ul><li>Renal function (methrotrexate, capecitabine, bisphosphonates) </li></ul><ul><li>Risk poor compliance (oral medications) </li></ul>
  13. 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
  14. 14. Growing population, with high incidence of disease, are under-represented in clinical trials <ul><li>Percentage of trial enrolment of patients ≥65 years old (Southwest Oncology Group [SWOG] 1993–1996) 1 </li></ul>1. Hutchins LF, et al. N Engl J Med 1999;341:2061–7 2. Droz JP, et al. Crit Rev Oncol Hematol 2008;68:S1–8 Percentage patients 70 60 50 40 30 20 10 0 Prostate Bladder Colorectal Lung Pancreatic Ovarian Soft-tissue sarcoma Leukaemia Myeloma Head and neck Melanoma Brain Lymphoma Breast Cervical
  15. 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. 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. 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. 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. 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
  20. 20. CALGB 49907: Adjuvant Combination Chemotherapy Superior to Monotherapy in Older Patients > 65 yrs <ul><li>Significant improvement in disease-free survival and overall survival with CMF/AC </li></ul>Age ≥65 Stage T1–4, N0–3, M0 Performance Status 0–2 Capecitabine x 6 (n=307) CMF (q4 x 6) or AC (q3w x 4) (n=326) Muss HB, et al. NEJM 2009; 360(20):2055–65 % patients without progression % patients surviving 1.0 0.8 0.6 0.4 0.2 0 0 1 2 3 4 5 Years CMF/AC Cape CMF/AC Cape p=0.0009 p=0.019 1.0 0.8 0.6 0.4 0.2 0 0 1 2 3 4 5 Years
  21. 21. Metastatic Breast Cancer Phase III Chemotherapy Trial in Older Patients <ul><li>First line chemotherapy MBC > 60 years (n= 397) </li></ul><ul><li>epirubicin (35 mg/m 2 iv) days 1, 8 15 q 28 days </li></ul><ul><li>vs </li></ul><ul><li>gemcitabine (1250 mg/m 2 iv) days 1, 8, 15 q 28 days </li></ul><ul><li>Better OS (19.1 vs 11.8 months, p = 0.0004) </li></ul><ul><li>Better TTP (6.1 vs 3.4 months, p = 0.0001) </li></ul><ul><li>Better RR (40.3% vs 16.4%, p < 0.001) </li></ul>
  22. 22. Metastatic Breast Cancer Trastuzumab, Bevacizumab <ul><li>Age is risk factor for cardiotoxicity with trastuzumab, especially if history of cardiac disease or diabetes – careful cardiac monitoring </li></ul><ul><li>Age > 65 years increased risk for arterial thrombo-embolism with bevacizumab based Rx for advanced cancer </li></ul>
  23. 23. Metastatic Breast Cancer Elderly Patients Help elderly patients and their loved ones choose the appropriate pathways

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