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PO68 TREATMENT WITH ERIBULIN (HALAVEN) IN HEAVILY PRE-TREATED PATIENTS WITH METASTATIC BREAST CANCER
Abstracts / The Breast 22 S3 (2013) S19–S63
PO67 CLINICAL BENEFIT OF ETHINYLESTRADIOL AS A SALVAGE ENDOCRINE THERAPY FOR THE HEAVILY PRETREATED METASTATIC BREAST CANCER Hirotaka Iwase1, Naoto Kondo2, Toshinari Yamashita3, Seigo Nakamura4, Masahiko Ikeda5, Tero Kawasoe6, Akiyo Horio2, Mutsuko YamamotoIbusuki1, Hiroji Iwata2, Yutaka Yamamoto1 1 Kumamoto University, Kumamoto, Japan; 2Aichi Cancer Center Hospital, Nagoya, Japan; 3Tokyo Metropolitan Komagome Hospital, Tokyo, Japan; 4 Showa University School of Medicine, Tokyo, Japan; 5Fukuyama City Hospital, Fukuyama, Japan; 6Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan Background: Estrogens usually stimulate the progression of estrogen receptor (ER) positive breast cancer. Paradoxically, high-dose estrogens may suppress the growth of these tumors in certain circumstances, such as after long-term estrogen deprivation therapies. Methods: A multi-center prospective cohort study (UMIN registration number; 000002831) was performed to evaluate the efficacy and safety of ethinylestradiol (EE2) treatment (1.5-3 mg/day, oral). Sixty-six postmenopausal patients (median age 62 years-old) with ER positive advanced or recurrent breast cancer were registered from Jan 2010 to Feb 2013. All of the patients were already treated by sequential endocrine therapies (median 4 lines), such as aromatase inhibitors, SERMs or fulvestrant. Chemotherapies (median; 2 lines) were also done for 70% of the patients. The dose of EE2, 1.5 mg or 3 mg/day, was chosen by the investigators considering the comorbidity or performance status of the patients. Results: In intent to treat analysis, the response rate was 30.3% (20/66) and the clinical benefit rate was 39.4% (26/66). The stable disease (< 6 months) was 21.2% (14/66) and progressive disease was 15.2% (10/66). Ten cases (15.2%) withdrew within 2 weeks due to early endocrine-related flare symptoms, such as nausea, vomiting, hot flush, muscle-skeletal pain. Another 6 cases was not able to evaluate the efficacy by any imaging. In the evaluable cases treated for over 4 weeks (n=49), RR was 40.8% (20/49) and CBR was 53.1% (26/49). Time to treatment failure in the 26 responders including 10 cases ongoing was a median of 7.5 months (range 2 to 14.5+). Vaginal bleeding or endometrial thickening was also frequently observed in patients receiving longterm treatment. Cerebral infarction as a severe adverse event was seen in one patient during this trial. There were no report of deep venous thrombosis and second malignancies. Additionally, some patients said that their skin and vaginal dryness was improved compared to during the aromatase inhibitor treatment. Conclusions: The mechanism of this estrogen tumor-suppressive action has been reported as estrogen-induced apoptosis. Although we should be careful to the adverse events, ethinylestradiol treatment (1.5-3 mg/ day) is beneficial as a salvage endocrine therapy for heavily pretreated metastatic breast cancer.
PO68 TREATMENT WITH ERIBULIN (HALAVEN) IN HEAVILY PRE-TREATED PATIENTS WITH METASTATIC BREAST CANCER M. Lynge1, G.I. Liposits2, S. Linnet2, S.T. Langkjer1 1 Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; 2 Department of Oncology, Herning Hospital, Herning, Denmark Background: There is a need of improvement of the currently available treatment for heavily pre-treated patients with metastatic breast cancer. Some patients become either refractory or do not respond to treatments involving antracyclines and taxanes. Eribulin is a non-taxane microtubule dynamics inhibitor. A randomised study has shown that eribulin monotherapy is superior to treatment of physician choice (The EMBRACE study 2011). The aim of this study was to evaluate eribulin treatment effects in real life patients focusing on antitumor activity, baseline characteristics, discontinuations of treatment and adverse events.
S43
Materials and Methods: Patients with breast cancer and in treatment with eribulin were examined retrospectively. Data was collected from 30 patients previously treated with either an anthracycline, a taxane or other cytotoxic chemotherapy. Patients were defined accordingly to status of ER and HER2 expression, most common metastatic sites and number of organs involved. Eribulin was administrated intravenously on day 1 and 8 of a 21 day cycle. Accordingly to registration of adverse events the results are based on patient prospectively reported side effects during treatment. Results: The median age of the patients was 53.6 years (range 4075 years). 33.3% (N=10) of the patients had luminal (A and B) type breast cancer, 50% (N=15) had HER-2 positive disease and 16.7% (N=5) had triple negative breast cancer (TNBC). The most common metastatic sites were bone (70%), liver (60%), lung (53.3%), and lymph nodes (53.3%). CNS metastases were reported in 5 cases (16.7%). Patients (N=30) had received a median of five prior chemotherapy regimens (range 2-7). Objective response rate (ORR) was 23.3%. Disease control rate (DCR=CR+PR+SD) was concluded 40% (N=12). The median number of doses administrated was 4.6 (range 1-12). Patients with luminal type cancer recieved median 6 cycles (range 2-12), HER-2 positive patients received median 3 cycles (2-7), and TNBC patients received median 3 cycles (2-5). Delayed dose administration and dose reduction were undertaken in respectively 37.7% and 23.3%. Adverse events were reported in 26 of 30 patients receiving Eribulin. CTCEA 3.0 version was applyed. The most common adverse events were fatigue (73.3%), peripheral neuropathy (46.7%), pyrexia (40%) and arthralgia/myalgia (36.7%). Of all reported graded adverse events (n= 106) 83% was grade 1 and 2 compared to only 17% (n=18) reported as grade 3 and 4. Conclusions: Eribulin seems to be an effective treatment option for heavily pre-treated patients with meatstatic breast cancer. Patients tolerate the eribulin administration very well as the profile of reported adverse events primarily involves grade 1 and 2. This in spite of the fact, that treatment with eribulin for many of the patients was the last line of chemotherapy before best supportive care.
PO69 ERIBULIN IN PRACTICE, REVIEW OF 70 CASES FROM SINGLE INSTITUTE AND COMPARISON WITH JAPAN PHASE 2 STUDY Junichiro Watanabe, Seiichiro Nishimura, Kaoru Takahashi Shizuoka Cancer Centre, Shizuoka, Japan Background: Eribulin mesylate, a novel microtubule dynamics modulator, demonstrated survival benefit or antitumor activity in metastatic breast cancer (MBC) patients (pts) in some clinical trials, although, utility of eribulin in practice has not been well discussed. Patients and Methods: MBC pts resistant to anthracycline (A) and taxane (T) were considered to receive eribulin. Eribulin mesylate of 1.4 mg/m2 (maximum 2.0 mg/body) administered on day(D)s 1 and 8 in 3-week cycle, unless neutrophil count was grade (G) 0/1 on D1 and G0-2 on D8. HER2+ patient received eribulin mesylate of 1.4 mg/m2 (max. 2.0 mg/body) on D1 concurrently with 6 mg/kg (loading dose 8 mg/ kg) of trastuzumab in 3-week cycle. Since prophylactic G-CSF was not approved, pt who showed G>2 neutropenia on any D1 or D8 underwent dose-reduction of eribulin mesylate from 1.4 to 1.1 mg/m2 subsequently to avoid febrile neutropenia (FN). Results: From July 2011 to June 2013, median age of 60 (range 31-76), 70 female MBC pts have been treated with eribulin. Receptor status was as follows; ER+ 48 (68.6%), HER2+ 16 (22.9%), triple-negative 14 (20.0%). They had received median 2 (range 1-12) prior chemotherapy regimens, and 84.3% of them had received A and/or T for MBC. Of 49 patients (70.0%) had visceral disease. Pts received median 4 cycles of eribulin (range 1-26). Concurrent trastuzumab was administered in 12 of 16 HER2+ pts. Relative dose intensity (RDI) of pts who received eribulin monotherapy >2 cycles was 68.05% (range 23.00-99.42). Median time to treatment-failure (TTF) was 119.0 days (95% confidence interval [CI]; 55.0-278.0) and median overall survival (OS) was 545.0 days (95%CI; 177.0-663.0). TTF was not influenced by ER, HER2, prior regimens,
PO67 CLINICAL BENEFIT OF ETHINYLESTRADIOL AS A SALVAGE ENDOCRINE THERAPY FOR THE HEAVILY PRETREATED METASTATIC BREAST CANCER Hirotaka Iwase1, Naoto Kondo2, Toshinari Yamashita3, Seigo Nakamura4, Masahiko Ikeda5, Tero Kawasoe6, Akiyo Horio2, Mutsuko YamamotoIbusuki1, Hiroji Iwata2, Yutaka Yamamoto1 1 Kumamoto University, Kumamoto, Japan; 2Aichi Cancer Center Hospital, Nagoya, Japan; 3Tokyo Metropolitan Komagome Hospital, Tokyo, Japan; 4 Showa University School of Medicine, Tokyo, Japan; 5Fukuyama City Hospital, Fukuyama, Japan; 6Japanese Red Cross Kumamoto Hospital, Kumamoto, Japan Background: Estrogens usually stimulate the progression of estrogen receptor (ER) positive breast cancer. Paradoxically, high-dose estrogens may suppress the growth of these tumors in certain circumstances, such as after long-term estrogen deprivation therapies. Methods: A multi-center prospective cohort study (UMIN registration number; 000002831) was performed to evaluate the efficacy and safety of ethinylestradiol (EE2) treatment (1.5-3 mg/day, oral). Sixty-six postmenopausal patients (median age 62 years-old) with ER positive advanced or recurrent breast cancer were registered from Jan 2010 to Feb 2013. All of the patients were already treated by sequential endocrine therapies (median 4 lines), such as aromatase inhibitors, SERMs or fulvestrant. Chemotherapies (median; 2 lines) were also done for 70% of the patients. The dose of EE2, 1.5 mg or 3 mg/day, was chosen by the investigators considering the comorbidity or performance status of the patients. Results: In intent to treat analysis, the response rate was 30.3% (20/66) and the clinical benefit rate was 39.4% (26/66). The stable disease (< 6 months) was 21.2% (14/66) and progressive disease was 15.2% (10/66). Ten cases (15.2%) withdrew within 2 weeks due to early endocrine-related flare symptoms, such as nausea, vomiting, hot flush, muscle-skeletal pain. Another 6 cases was not able to evaluate the efficacy by any imaging. In the evaluable cases treated for over 4 weeks (n=49), RR was 40.8% (20/49) and CBR was 53.1% (26/49). Time to treatment failure in the 26 responders including 10 cases ongoing was a median of 7.5 months (range 2 to 14.5+). Vaginal bleeding or endometrial thickening was also frequently observed in patients receiving longterm treatment. Cerebral infarction as a severe adverse event was seen in one patient during this trial. There were no report of deep venous thrombosis and second malignancies. Additionally, some patients said that their skin and vaginal dryness was improved compared to during the aromatase inhibitor treatment. Conclusions: The mechanism of this estrogen tumor-suppressive action has been reported as estrogen-induced apoptosis. Although we should be careful to the adverse events, ethinylestradiol treatment (1.5-3 mg/ day) is beneficial as a salvage endocrine therapy for heavily pretreated metastatic breast cancer.
PO68 TREATMENT WITH ERIBULIN (HALAVEN) IN HEAVILY PRE-TREATED PATIENTS WITH METASTATIC BREAST CANCER M. Lynge1, G.I. Liposits2, S. Linnet2, S.T. Langkjer1 1 Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; 2 Department of Oncology, Herning Hospital, Herning, Denmark Background: There is a need of improvement of the currently available treatment for heavily pre-treated patients with metastatic breast cancer. Some patients become either refractory or do not respond to treatments involving antracyclines and taxanes. Eribulin is a non-taxane microtubule dynamics inhibitor. A randomised study has shown that eribulin monotherapy is superior to treatment of physician choice (The EMBRACE study 2011). The aim of this study was to evaluate eribulin treatment effects in real life patients focusing on antitumor activity, baseline characteristics, discontinuations of treatment and adverse events.
S43
Materials and Methods: Patients with breast cancer and in treatment with eribulin were examined retrospectively. Data was collected from 30 patients previously treated with either an anthracycline, a taxane or other cytotoxic chemotherapy. Patients were defined accordingly to status of ER and HER2 expression, most common metastatic sites and number of organs involved. Eribulin was administrated intravenously on day 1 and 8 of a 21 day cycle. Accordingly to registration of adverse events the results are based on patient prospectively reported side effects during treatment. Results: The median age of the patients was 53.6 years (range 4075 years). 33.3% (N=10) of the patients had luminal (A and B) type breast cancer, 50% (N=15) had HER-2 positive disease and 16.7% (N=5) had triple negative breast cancer (TNBC). The most common metastatic sites were bone (70%), liver (60%), lung (53.3%), and lymph nodes (53.3%). CNS metastases were reported in 5 cases (16.7%). Patients (N=30) had received a median of five prior chemotherapy regimens (range 2-7). Objective response rate (ORR) was 23.3%. Disease control rate (DCR=CR+PR+SD) was concluded 40% (N=12). The median number of doses administrated was 4.6 (range 1-12). Patients with luminal type cancer recieved median 6 cycles (range 2-12), HER-2 positive patients received median 3 cycles (2-7), and TNBC patients received median 3 cycles (2-5). Delayed dose administration and dose reduction were undertaken in respectively 37.7% and 23.3%. Adverse events were reported in 26 of 30 patients receiving Eribulin. CTCEA 3.0 version was applyed. The most common adverse events were fatigue (73.3%), peripheral neuropathy (46.7%), pyrexia (40%) and arthralgia/myalgia (36.7%). Of all reported graded adverse events (n= 106) 83% was grade 1 and 2 compared to only 17% (n=18) reported as grade 3 and 4. Conclusions: Eribulin seems to be an effective treatment option for heavily pre-treated patients with meatstatic breast cancer. Patients tolerate the eribulin administration very well as the profile of reported adverse events primarily involves grade 1 and 2. This in spite of the fact, that treatment with eribulin for many of the patients was the last line of chemotherapy before best supportive care.
PO69 ERIBULIN IN PRACTICE, REVIEW OF 70 CASES FROM SINGLE INSTITUTE AND COMPARISON WITH JAPAN PHASE 2 STUDY Junichiro Watanabe, Seiichiro Nishimura, Kaoru Takahashi Shizuoka Cancer Centre, Shizuoka, Japan Background: Eribulin mesylate, a novel microtubule dynamics modulator, demonstrated survival benefit or antitumor activity in metastatic breast cancer (MBC) patients (pts) in some clinical trials, although, utility of eribulin in practice has not been well discussed. Patients and Methods: MBC pts resistant to anthracycline (A) and taxane (T) were considered to receive eribulin. Eribulin mesylate of 1.4 mg/m2 (maximum 2.0 mg/body) administered on day(D)s 1 and 8 in 3-week cycle, unless neutrophil count was grade (G) 0/1 on D1 and G0-2 on D8. HER2+ patient received eribulin mesylate of 1.4 mg/m2 (max. 2.0 mg/body) on D1 concurrently with 6 mg/kg (loading dose 8 mg/ kg) of trastuzumab in 3-week cycle. Since prophylactic G-CSF was not approved, pt who showed G>2 neutropenia on any D1 or D8 underwent dose-reduction of eribulin mesylate from 1.4 to 1.1 mg/m2 subsequently to avoid febrile neutropenia (FN). Results: From July 2011 to June 2013, median age of 60 (range 31-76), 70 female MBC pts have been treated with eribulin. Receptor status was as follows; ER+ 48 (68.6%), HER2+ 16 (22.9%), triple-negative 14 (20.0%). They had received median 2 (range 1-12) prior chemotherapy regimens, and 84.3% of them had received A and/or T for MBC. Of 49 patients (70.0%) had visceral disease. Pts received median 4 cycles of eribulin (range 1-26). Concurrent trastuzumab was administered in 12 of 16 HER2+ pts. Relative dose intensity (RDI) of pts who received eribulin monotherapy >2 cycles was 68.05% (range 23.00-99.42). Median time to treatment-failure (TTF) was 119.0 days (95% confidence interval [CI]; 55.0-278.0) and median overall survival (OS) was 545.0 days (95%CI; 177.0-663.0). TTF was not influenced by ER, HER2, prior regimens,