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F13 AML: How to characterize and treat elderly patients non fit for standard treatment
S10
Critical Reviews in Oncology/Hematology 72S1 (2009)
At a median of 7 years follow-up, the difference in DFS between TC and AC was significant (81% TC v 75% AC; P = 0.033; hazard ratio [HR], 0.74; 95% CI 0.56 to 0.98) as was OS (87% TC v 82% AC; P = 0.032; HR, 0.69; 95% CI 0.50 to 0.97). TC was superior in older patients as well as younger patients. There was no interaction of hormone-receptor status or HER-2 status and treatment. Older women experienced more febrile neutropenia with TC and more anemia with AC. Reference(s) Muss HB, Berry DA, Cirrincione CT, et al. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009; 360:2055−65 Wildiers H, Jurcut R, Ganame J, et al. A pilot study to investigate the feasibility and cardiac effects of pegylated liposomal doxorubicin (PL-DOX) as adjuvant therapy in medically fit elderly breast cancer patients. Crit Rev Oncol Hematol. 2008; 67: 133−8. Jones S, Holmes FA, O’Shaughnessy J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009; 27: 1177−83
F10 How to evaluate the heart of the elderly patients M. Ewer *. M.D. Anderson Cancer Center, Houston, TX, USA Abstract not available at time of printing. F11 Evidence in favor of taxane based combinations and no anthracycline in adjuvant and metastatic settings N. Harbeck *. Breast Center, University of Cologne, Cologne, Germany Purpose of the study: In breast cancer, anthracyclines and taxanes are the most effective chemotherapeutic agents and thus part of various standard regimens. In a potentially curable disease such as early breast cancer (EBC) but also in a chronic disease such as metastatic breast cancer (MBC), acute and delayed cardiotoxicity associated with anthracycline therapy is an issue that needs to be addressed. In particular, combined use of anthracyclines and targeted agents such as trastuzumab, lapatinib, or bevacizumab may cause cardiac problems. Method(s): Recently, several anthracycline (A)-free regimens have been proposed in the literature with efficacy data comparing well or even showing superiority to anthracycline-containing regimens. Result(s): For EBC, the TC (docetaxel-cyclophosphamide) regimen has been shown to be more effective than 4xAC regarding disease-free and overall survival. In subgroup analyses, this superiority was also seen independent of nodal status and patient age (Jones et al, JCO 2009). In HER2 positive disease, the BCIRG 006 trial showed that TCH (docetaxelcarboplatinum-trastuzumab) was as effective as AC → docetaxel regarding DFS and OS, again independent of nodal status (Slamon et al, SABCS 2006 and 2007). For MBC, numerous effective chemotherapeutic agents are available. Next to disease burden and patient preference, adjuvant pretreatment needs to be considered before deciding upon a certain option. If anthracycline-use is indicated, cumulative A-dose after adjuvant therapy and cardiac toxicity thresholds (doxorubicin ~500 mg/m2 ; epirubicin ~950 mg/m2 ) most likely warrant caution regarding use of free anthracyclines. Yet, liposomal formulations may still be a reasonable option. If additional targeted therapy is warranted, mostly taxanes and other nonanthracycline agents are validated combination partners, such as taxane + trastuzumab or capecitabine + lapatinib for HER2 positive or paclitaxel, docetaxel, or capecitabine + bevacizumab for HER2 negative disease. In particular, for taxanes, re-challenge after adjuvant use is possible and effective if a disease-free interval of 12 months or more has been achieved. Conclusion(s): A-free chemotherapy regimens are important and effective options in early and metastatic breast cancer, particularly for patients with co-morbidities or if combinations with targeted agents are warranted. While numerous chemotherapeutic options exist for MBC, TC for HER2 negative and TCH for HER2 positive disease are the best documented A-free options in early disease. The German AGO guidelines recommend these regimens with “+” if use of anthracyclines is not indicated. Yet, caution needs to be applied. Anthracyclines are among the most potent agents for breast cancer therapy and it is not yet clear, which A-free
10th SIOG Meeting, October 15–17, 2009, Berlin, Germany regimens can be safely used for which patient and risk group, in particular in the potentially curable early disease setting. Therefore, ongoing clinical EBC trials such as WSG Plan B or SUCCESS C in Germany are essential. F12 How safe is bevacizumab for elderly patients? X. Pivot1,2 *, C. Villanueva1 , F. Bazan1 , A. Thierry-Vuillemin1,2 , L. Chaigneau1 , E. Dobi1 , E. Curtit1 , L. Cals1 . 1 University Hospital J. Minjoz, Besan¸con, France, 2 Institut National de la Sant´e et de la Recherche M´edicale, Unit 645, Besan¸con, France Purpose of the study: Bevacizumab (BV) reached marketing authorization for its use in Europe and in the US in first line metastatic breast cancer (mBC) in association with taxanes [either docetaxel (D) or paclitaxel (P)]. Due to the specific ways of action reported for BV, one might wonder whether this compound is safe for the treatment of elderly patients. Method(s): Two subset analyses performed in elderly population in order to assess the safety and efficacy profile of BV [1,2] were presented at ASCO 2009. They were the AVADO and the MO19391 studies, carried out among pts aged 65 and 70 years, respectively. The AVADO study randomized BV 7.5 or 15 mg/kg or placebo + D 100mg/m2 in 736 pts in first line treatment for mBC. As for MO19391, it is an observational study in 2041 patients with mBC receiving first line BV-containing therapy. Results: In the AVADO study, among the 127 (17.3% of the total population) pts aged 65 years, pts had a similar treatment benefit compared to the entire study population. BV had limited additional impact on the known side effects of D. No grade 3 GI perforation, wound-healing complications, CHF or proteinuria were reported. In the MO19391 trial among the 171 (8% of the total population) pts aged 70 years, no increase in grade 3 toxicity was reported but hypertension. Grade 3 hypertension appeared to be more common among older subpopulation (7% versus 4% in the younger subset). Conclusions: In these retrospective analyses, the addition of BV was generally well tolerated in elderly pts with mBC. The magnitude of the benefit in pts aged 65 years in the AVADO trial was similar to that in the overall study population but failed to reach statistical significance, probably due to the small sample size. Reference(s) [1] L Biganzoli et al. Tolerability and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced breast cancer: subpopulation analysis of the MO19391 study. 45th annual meeting of the Am. Soc. Med Oncol. Abstr 1032, 2009. [2] X Pivot et al. Clinical benefit of bevacizumab + first-line docetaxel in patients with locally recurrent or metastatic breast cancer: AVADO study. 45th annual meeting of the Am. Soc. Med Oncol. Abstr 1994, 2009.
Saturday, October 17, 2009 08.00–09.20
Parallel Session V-a: Hematological malignancies F13 AML: How to characterize and treat elderly patients non fit for standard treatment K. Spiekermann *. Department of Internal Medicine III, University of Munich, Munich, Germany Abstract not available at time of printing. F14 MDS: a challenge, especially in elderly patients R. Stauder *. Department of Internal Medicine V, Haematology and Oncology, Innsbruck Medical University, Innsbruck, Austria Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal myeloid neoplasms that are preferentially diagnosed in the elderly. Actually, the median age at diagnosis is 72 years in the D¨usseldorf and
Critical Reviews in Oncology/Hematology 72S1 (2009)
At a median of 7 years follow-up, the difference in DFS between TC and AC was significant (81% TC v 75% AC; P = 0.033; hazard ratio [HR], 0.74; 95% CI 0.56 to 0.98) as was OS (87% TC v 82% AC; P = 0.032; HR, 0.69; 95% CI 0.50 to 0.97). TC was superior in older patients as well as younger patients. There was no interaction of hormone-receptor status or HER-2 status and treatment. Older women experienced more febrile neutropenia with TC and more anemia with AC. Reference(s) Muss HB, Berry DA, Cirrincione CT, et al. Adjuvant chemotherapy in older women with early-stage breast cancer. N Engl J Med. 2009; 360:2055−65 Wildiers H, Jurcut R, Ganame J, et al. A pilot study to investigate the feasibility and cardiac effects of pegylated liposomal doxorubicin (PL-DOX) as adjuvant therapy in medically fit elderly breast cancer patients. Crit Rev Oncol Hematol. 2008; 67: 133−8. Jones S, Holmes FA, O’Shaughnessy J, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009; 27: 1177−83
F10 How to evaluate the heart of the elderly patients M. Ewer *. M.D. Anderson Cancer Center, Houston, TX, USA Abstract not available at time of printing. F11 Evidence in favor of taxane based combinations and no anthracycline in adjuvant and metastatic settings N. Harbeck *. Breast Center, University of Cologne, Cologne, Germany Purpose of the study: In breast cancer, anthracyclines and taxanes are the most effective chemotherapeutic agents and thus part of various standard regimens. In a potentially curable disease such as early breast cancer (EBC) but also in a chronic disease such as metastatic breast cancer (MBC), acute and delayed cardiotoxicity associated with anthracycline therapy is an issue that needs to be addressed. In particular, combined use of anthracyclines and targeted agents such as trastuzumab, lapatinib, or bevacizumab may cause cardiac problems. Method(s): Recently, several anthracycline (A)-free regimens have been proposed in the literature with efficacy data comparing well or even showing superiority to anthracycline-containing regimens. Result(s): For EBC, the TC (docetaxel-cyclophosphamide) regimen has been shown to be more effective than 4xAC regarding disease-free and overall survival. In subgroup analyses, this superiority was also seen independent of nodal status and patient age (Jones et al, JCO 2009). In HER2 positive disease, the BCIRG 006 trial showed that TCH (docetaxelcarboplatinum-trastuzumab) was as effective as AC → docetaxel regarding DFS and OS, again independent of nodal status (Slamon et al, SABCS 2006 and 2007). For MBC, numerous effective chemotherapeutic agents are available. Next to disease burden and patient preference, adjuvant pretreatment needs to be considered before deciding upon a certain option. If anthracycline-use is indicated, cumulative A-dose after adjuvant therapy and cardiac toxicity thresholds (doxorubicin ~500 mg/m2 ; epirubicin ~950 mg/m2 ) most likely warrant caution regarding use of free anthracyclines. Yet, liposomal formulations may still be a reasonable option. If additional targeted therapy is warranted, mostly taxanes and other nonanthracycline agents are validated combination partners, such as taxane + trastuzumab or capecitabine + lapatinib for HER2 positive or paclitaxel, docetaxel, or capecitabine + bevacizumab for HER2 negative disease. In particular, for taxanes, re-challenge after adjuvant use is possible and effective if a disease-free interval of 12 months or more has been achieved. Conclusion(s): A-free chemotherapy regimens are important and effective options in early and metastatic breast cancer, particularly for patients with co-morbidities or if combinations with targeted agents are warranted. While numerous chemotherapeutic options exist for MBC, TC for HER2 negative and TCH for HER2 positive disease are the best documented A-free options in early disease. The German AGO guidelines recommend these regimens with “+” if use of anthracyclines is not indicated. Yet, caution needs to be applied. Anthracyclines are among the most potent agents for breast cancer therapy and it is not yet clear, which A-free
10th SIOG Meeting, October 15–17, 2009, Berlin, Germany regimens can be safely used for which patient and risk group, in particular in the potentially curable early disease setting. Therefore, ongoing clinical EBC trials such as WSG Plan B or SUCCESS C in Germany are essential. F12 How safe is bevacizumab for elderly patients? X. Pivot1,2 *, C. Villanueva1 , F. Bazan1 , A. Thierry-Vuillemin1,2 , L. Chaigneau1 , E. Dobi1 , E. Curtit1 , L. Cals1 . 1 University Hospital J. Minjoz, Besan¸con, France, 2 Institut National de la Sant´e et de la Recherche M´edicale, Unit 645, Besan¸con, France Purpose of the study: Bevacizumab (BV) reached marketing authorization for its use in Europe and in the US in first line metastatic breast cancer (mBC) in association with taxanes [either docetaxel (D) or paclitaxel (P)]. Due to the specific ways of action reported for BV, one might wonder whether this compound is safe for the treatment of elderly patients. Method(s): Two subset analyses performed in elderly population in order to assess the safety and efficacy profile of BV [1,2] were presented at ASCO 2009. They were the AVADO and the MO19391 studies, carried out among pts aged 65 and 70 years, respectively. The AVADO study randomized BV 7.5 or 15 mg/kg or placebo + D 100mg/m2 in 736 pts in first line treatment for mBC. As for MO19391, it is an observational study in 2041 patients with mBC receiving first line BV-containing therapy. Results: In the AVADO study, among the 127 (17.3% of the total population) pts aged 65 years, pts had a similar treatment benefit compared to the entire study population. BV had limited additional impact on the known side effects of D. No grade 3 GI perforation, wound-healing complications, CHF or proteinuria were reported. In the MO19391 trial among the 171 (8% of the total population) pts aged 70 years, no increase in grade 3 toxicity was reported but hypertension. Grade 3 hypertension appeared to be more common among older subpopulation (7% versus 4% in the younger subset). Conclusions: In these retrospective analyses, the addition of BV was generally well tolerated in elderly pts with mBC. The magnitude of the benefit in pts aged 65 years in the AVADO trial was similar to that in the overall study population but failed to reach statistical significance, probably due to the small sample size. Reference(s) [1] L Biganzoli et al. Tolerability and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced breast cancer: subpopulation analysis of the MO19391 study. 45th annual meeting of the Am. Soc. Med Oncol. Abstr 1032, 2009. [2] X Pivot et al. Clinical benefit of bevacizumab + first-line docetaxel in patients with locally recurrent or metastatic breast cancer: AVADO study. 45th annual meeting of the Am. Soc. Med Oncol. Abstr 1994, 2009.
Saturday, October 17, 2009 08.00–09.20
Parallel Session V-a: Hematological malignancies F13 AML: How to characterize and treat elderly patients non fit for standard treatment K. Spiekermann *. Department of Internal Medicine III, University of Munich, Munich, Germany Abstract not available at time of printing. F14 MDS: a challenge, especially in elderly patients R. Stauder *. Department of Internal Medicine V, Haematology and Oncology, Innsbruck Medical University, Innsbruck, Austria Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal myeloid neoplasms that are preferentially diagnosed in the elderly. Actually, the median age at diagnosis is 72 years in the D¨usseldorf and