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Background The Safari study (UMIN000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive advanced breast cancer treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure in patients with estrogen receptor-positive advanced breast cancer. The current study is an ad hoc analysis that focused on the relationship between the patient factors and overall survival after recurrence by adding factors generally associated with overall survival after recurrence. Methods The overall survival after recurrence in patients with estrogen receptor-positive human epidermal growth factor receptor 2 negative recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model. Results A total of 598 cases were used for the analysis of overall survival after recurrence. Multivariate analysis revealed that favorable overall survival (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥3 years), low nuclear or histological grade (G3 vs. G1), long time to treatment failure of initial palliative endocrine therapy (≥12 months) and long time to initial palliative chemotherapy (≥2 years). Conclusion The results of this study indicate that sequential endocrine monotherapy may be a useful treatment option for patients with estrogen receptor-positive/human epidermal growth factor receptor 2 negative recurrent breast cancer who have been successfully treated with initial long-term palliative endocrine therapy.

Background: Only old evidence exist to back up the use of medroxyprogesterone acetate (MPA) in endocrine therapy. Therefore, this study aimed to explore the factors that influence the time to treatment failure (TTF) of MPA in real world settings as late-line treatment following aromatase inhibitors and fulvestrant. Methods: This was a cohort study that used the database of the Safari study, on estrogen receptor-positive (ER+) post-menopausal advanced breast cancer previously treated with fulvestrant (UMIN000015168). We created Kaplan-Meier curves for TTF treated with MPA. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the TTF of MPA. Results: Fist, we made Kaplan-Meier curves by treatment line for MPA in TTF analysis population 1 (n = 244), excluding HER2+ and HER2 with unknown status. The median TTF for MPA was 8.2 months (95% CI 5.1–14.9) for first- and second-line treatments, 3.0 months (95% CI 2.5–3.9) for third-line treatment, and 4.1 months (95% CI 3.5–5.0) for fourth or later treatment lines. The first- and second-line treatments had significantly longer TTF than the third-line treatment (P < 0.001) and fourth-line or later treatments (P < 0.001). No difference in TTF was observed between the third and fourth or later treatment lines. Similar results were obtained in the analysis population 2 (n = 203) for TTF, excluding cases in which MPA was considered to have been used in palliative care. The median TTF for MPA was 7.9 months (95% CI, 5.1-16.0) for first- and second-line treatments, 3.0 months (95% CI 2.8–4.6) for third-line treatment, and 4.3 months (95% CI 3.7–5.6) for fourth or later treatment lines. The first- and second-line treatments had significantly longer TTF than the third-line treatment (P < 0.001) and the fourth-line or later treatments (P < 0.001). No difference in TTF was observed between the third and fourth or later treatment lines. Second, Table 1 shows the clinicopathological factors involved in the TTF of MPA. In univariate analysis, long DFI (≥ 6 years), small nuclear or histological grade, and the presence of visceral metastases correlated with significantly long TTF (P < 0.05). Whereas PgR, adjuvant chemotherapy, and adjuvant endocrine therapy did not affect the TTF of patients treated with MPA. However, in the multivariate regression analysis, only longer DFI (≥ 6 years) was correlated with a significantly longer TTF. Third, we compared the clinicopathologic factors in the groups that received MPA as the fourth or later treatment lines and achieved a TTF of more than 1 year with those that did not. There were no characteristic clinicopathological factors distinct between the two groups. Conclusion: In actual clinical practice, patients treated with MPA alone as the fourth or subsequent treatment lines showed a TTF of 4 months, suggesting that there is merit in using MPA even in late treatment lines, especially in patients with long DFI and those who are difficult to treat with other antineoplastic agents. Table 1. Univariate and Multivariate analyses to investigate association between clinicopathological factors and TTF of MPA (n=170) Citation Format: Kaho Utsunomiya, Hidetoshi Kawaguchi, Yutaka Yamamoto, Shigehira Saji, Norikazu Masuda, Takahiro Nakayama, Kenjiro Aogi, Keisei Anan, Shoichiro Ohtani, Nobuaki Sato, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Satoshi Morita, Miki Yamaguchi, Toshinari Yamashita, Daisuke Yotsumoto, Masakazu Toi, Shinji Ohno. Retrospective study using database for the effectiveness of medroxyprogesterone acetate in patients with ER-positive/HER2-negative postmenopausal advanced breast cancer: An additional analysis of the JBCRG-C06 Safari study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-15.

BackgroundOnly old evidence exists to back up the use of medroxyprogesterone acetate. Therefore, this study aimed to explore the factors that influence the time to treatment failure of medroxyprogesterone acetate in real-world settings as late-line treatment.MethodsThis was a cohort study that used the database of the Safari study on oestrogen receptor-positive post-menopausal advanced breast cancer (UMIN000015168). We created Kaplan–Meier curves for time to treatment failure with medroxyprogesterone acetate. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the time to treatment failure of medroxyprogesterone acetate.ResultsFrom the 1031 patients in the Safari study, 279 patients were selected as the population for the analysis of effectiveness of medroxyprogesterone acetate monotherapy. In the analysis of medroxyprogesterone acetate by treatment line, the median time to treatment failure was 3.0 months for third-line treatment and 4.1 months for fourth and subsequent treatment lines. In cases where medroxyprogesterone acetate was used as a third-line or later endocrine treatment, multivariate analysis showed that the length of the disease-free interval was correlated with the length of time to treatment failure of medroxyprogesterone acetate (P = 0.004). With medroxyprogesterone acetate monotherapy as the fourth-line or later treatment, 20% of the patients achieved a time to treatment failure of 12 months or longer.ConclusionIn actual clinical practice, patients treated with medroxyprogesterone acetate alone as the fourth or subsequent treatment lines showed a time to treatment failure of 4 months, suggesting that there is merit in using medroxyprogesterone acetate even in late treatment lines, especially in patients with long disease-free interval and those who are difficult to treat using other antineoplastic agents.

Aim To assess the utility of the perioperative use of direct oral anticoagulants for patients with hepatocellular carcinoma (HCC) with cancer-associated thrombosis. Case report An 83-year-old woman was admitted with a solitary HCC (10-cm diameter), as well as with multiple sites of venous thromboembolism and macroscopic portal vein tumor thrombosis. She had appropriate liver function without viral hepatitis, triple-positive tumor markers, and secondary polycythemia. Edoxaban at 30 mg was initiated 10 days before surgery to remove HCC. Complete remission of the pulmonary embolism and stability of the deep vein thrombosis and massive superior mesenteric vein thrombosis were recognized preoperatively. An extended left hepatectomy was successfully performed. To avoid hemorrhage complications, we used intravenous administration of nafamostat mesylate for 2 days, thereafter we restarted edoxaban. Superior mesenteric vein thrombosis resolved 5 months after surgery. Conclusion Perioperative oral administration of edoxaban was useful in multidisciplinary treatment for a patient with advanced HCC with cancer-associated thrombosis.

SummaryPurpose To date, it is not clear which anticancer agent is useful in combination with trastuzumab and pertuzumab As the first and second selective regimens for advanced or metastatic breast cancer (AMBC), this multicenter, open-label, phase II trial (JBCRG-M03: UMIN000012232) presents a prespecified analysis of eribulin in combination with pertuzumab and trastuzumab. Methods We enrolled 50 patients with no or single prior chemotherapy for HER2-positive AMBC during November 2013–April 2016. All patients received adjuvant or first-line chemotherapy with trastuzumab and a taxane. The treatment comprised eribulin on days 1 and 8 of a 21-day cycle and trastuzumabplus pertuzumab once every 3 weeks, all administered intravenously. While the primary endpoint was the progression-free survival (PFS), secondary endpoints were the response rate and safety. Results Of 50 patients, 49 were eligible for safety analysis, and the full analysis set (FAS) included 46 patients. We treated 8 (16%) and 41 (84%) patients in first- and second-line settings, respectively. While 11 patients (23.9%) had advanced disease, 35 (76.1%) had metastatic disease. The median PFS was 9.2 months for all patients [95% confidence interval (CI): 7.0–11.4]. In the FAS, 44 patients had the measurable lesions and the complete response rate (CR) was 17.4%, and partial response rate (PR) was 43.5%. The grade 3/4 adverse events were neutropenia (5 patients, 10.2%), including febrile neutropenia (2 patients, 4.1%), hypertension (3 patients, 6.1%), and other (1 patient). The average of the left ventricular ejection fraction did not decline markedly. No symptomatic left ventricular systolic dysfunction was observed. Conclusions In patients with HER2-positive AMBC, eribulin, pertuzumab, and trastuzumab combination therapy exhibited substantial antitumor activity with an acceptable safety profile. Hence, we have started a randomized phase III study comparing eribulin and a taxane in combination with pertuzumab and trastuzumab for the treatment of HER2-positive AMBC. Trial registration ID: UMIN-CTR: UMIN000012232.

Purpose To investigate the effectiveness and safety of bevacizumab–paclitaxel combination therapy as first- or second-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer in daily clinical practice. Methods In this prospective multicenter observational study, bevacizumab–paclitaxel was administered at the discretion of attending physicians. Cohorts A and B had hormone receptor-positive and triple-negative breast cancer (TNBC), respectively. Primary endpoint was overall survival (OS). Multivariate analyses were conducted to identify prognostic factors. Results Between November 2012 and October 2014, 767 patients were enrolled from 155 institutions across Japan. Effectiveness was analyzed in 754 eligible patients (cohort A, 539; cohort B, 215) and safety in 750 treated patients (median observation period, 19.7 months). Median OS (95% CI) was 21.7 (19.8–23.6) months in eligible patients; 25.2 (22.4–27.4) months and 13.2 (11.3–16.6) months in cohorts A and B, respectively; and 24.4 (21.9–27.2) months and 17.6 (15.2–20.0) months in patients receiving first- and second-line therapy, respectively. Factors affecting OS (hazard ratio 95% CI) were TNBC (1.75, 1.44–2.14), second-line therapy (1.35, 1.13–1.63), ECOG performance status ≥ 1 (1.28, 1.04–1.57), taxane-based chemotherapy (0.65, 0.49–0.86), cancer-related symptoms (0.56, 0.46–0.68), and visceral metastasis (0.52, 0.40–0.66). Incidences of grade ≥ 3 AEs hypertension, neutropenia, peripheral neuropathy, proteinuria, and bleeding were 35.7%, 27.2%, 7.2%, 3.7%, and 0.3%, respectively. Conclusions In Japanese clinical practice, combined bevacizumab–paclitaxel was as effective as in previous studies. Factors that independently predicted poor prognosis in the present study are consistent with those identified previously. Trial registration Trial no. UMIN000009086.

Background: There are now many treatment options for estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC). However, there are few reports indicating the optimal treatment sequence for this disease. Information to predict response to treatment is vital for personalized therapy and determining the most beneficial approach for individual patients. In this study, we attempted to determine predictive factors of response to hormonal therapy and survival outcomes using the large-scale databases constructed in the Safari study (UMIN000015168), a retrospective, multicenter cohort study involving 1,072 Japanese patients receiving fulvestrant 500mg for ER+ ABC. We examined the association between clinicopathological factors and time to failure (TTF) of fulvestrant in Japanese ABC patients. Methods: Among 1072 patients, 247 patients were selected for this study. Inclusion criteria was as follows: 1) patients treated with either SERM or AI in the adjuvant setting (AS) with known starting and finishing date of the treatment (patients relapsed on adjuvant treatment were excluded), 2) patients treated with SERM, AI and SERD in the metastatic setting (MS) as the first and the second line treatment. Influence of the adjuvant hormonal therapy on the TTF of the first line and the second line treatment and overall survival (OS) was assessed. Cox proportional hazards model was used for this analysis. Results: Patients treated with SERM in AS had significantly longer TTF of 1st line and 1st+2nd line of hormonal therapy in MS (1st line: HR 1.519, 95% CI 1.04-2.218, p=0.0307, 1st+2nd line: HR 2.372, 95% CI 1.584-3.551, p Conclusions: Interestingly, once AI-treated patients in AS have relapsed, their hormone sensitivity is lower and survival outcomes are worse compared with SERM-treated patients in AS in this cohort. Our results have consistency with the results of ABCSG-12 trial showing a pronounced higher risk of death for anastrozole-treated patients (Annals of Oncology 26: 313–320, 2015). Since it is a cohort of selected patients who were successfully treated with fulvestrant, prospective analysis would be therefore warranted. Citation Format: Takahiro Nakayama, Hidetoshi Kawaguchi, Norikazu Masuda, Kenjiro Aogi, Keisei Anan, Yoshinori Ito, Shoichiro Ohtani, Nobuaki Sato, Shigehira Saji, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Satoshi Morita, Miki Yamaguchi, Hiroko Yamashita, Toshinari Yamashita, Yutaka Yamamoto, Daisuke Yotsumoto, Masakazu Toi, Shinji Ohno. Influence of the adjuvant hormonal therapy on hormone sensitivity and survival outcomes in ER+ and HER2−advanced breast cancer: A subgroup analysis of the JBCRG-C06 Safari study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-11.

Background: After the CONFIRM trial, fulvestrant 500 mg (F500) became a standard treatment for patients with estrogen receptor positive (ER+) advanced/metastatic breast cancer (AMBC). The JBCRG-C06 Safari study (UMIN 000015168) showed that earlier F500 use, a longer time from diagnosis to F500 use, and no prior chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with ER+ and HER2-negative AMBC (Kawaguchi H, et al. Breast Cancer Res Treat, 2017; Kawaguchi H, et al. Curr Med Res Opin, 2018). We had carried out subgroup analyses on real world data from the Safari study focusing on ER+ and HER2+ AMBC with the objective to examine further on potential interactions between TTF and the following: F500 single treatment or F500 with anti-HER2 therapy; presence or absence of visceral metastasis; progesterone receptor (PgR) status; and prior chemotherapy for AMBC. Material & methods: The Safari study was a retrospective, multicenter cohort study, conducted in 1072 patients at 16 sites in Japan for ER+ AMBC. Patients starting treatment with F500 between Nov 2011 and Dec 2014 were registered. After the data cleaning through the central review, 94 patients (9.6%) has been included in this sub-analysis among the 978 patients in which HER2 status was confirmed by the documentation. The relationship between baseline clinical/pathological factors, treatment line, and TTF (time from start to cessation of F500 treatment for any reason, including toxicity and death) were analyzed using Kaplan-Meier methods. Univariate analysis of TTF data was performed by Cox hazards model using: age, histological type, histological/nuclear grade, visceral-metastases, stage, PgR, period from AMBC diagnosis to F500 use, treatment line of F500, prior chemotherapy. Results: Median age at diagnosis of AMBC was 57.5yrs (33-85); 59(33-85) and 56.5(39-75) for F500 with/ without anti-HER2 therapy. Median age of fulvestrant start was 61yrs (35-96). 21.3% had de novo metastatic disease; 78.7% recurrent disease; 37.2% visceral metastases. All patients’ ER status was positive, and PgR status was positive in 65.9%, negative 25.5% respectively. HER2 IHC 3+ patients accounted for 44.7%, IHC 2+/1+ for 38.3%. In the case of IHC 2+/1+, HER2-positivity was confirmed by FISH. F500 alone was administered in 52 patients, while F500 with anti-HER2 therapy in 42 patients. At median follow up of 3.9 years, median TTF was 4.4m (95% CI: 3.3-5.7); 3.7m (95% CI: 2.9-5.9), 5.1m(95% CI: 3.6-6.4) for the F500 alone group, F500 with anti-HER2 therapy group respectively (p = 0.5973). F500 with/ without anti-HER2 therapy was administered in 1stor 2nd-line in 20 (21.3%), and ≥3rd-line in 74(78.7%) patients. Median TTF was 6.6m (95% CI: 4.6-8.5) and 3.7m (95% CI: 2.8-5.2) in the 1stor 2nd-line and ≥3rd-line respectively (p value:0.0145). Although no statistically significant difference was found, TTF tended to be shorter in the group receiving chemotherapy prior to F500 (median TTF: 3.7m vs 5.5m). No other clinical parameters including age, PgR status, metastatic sites were associated with the effectiveness. The median OS was 7.8-years (95% CI: 5.9-9.5), which had not been influenced by with/ without anti-HER2 therapy. The toxicity profile we observed was similar to that in the registration trial. Conclusions: Our findings suggest that F500 with/without anti-HER2 therapy appears to be effective also in the ER+ and HER2-positive ABMC setting which is consistent with the limited results previously published. Earlier line use of F500 use may be useful in HER2-positive patients as well as HER2-negative patients. Citation Format: Misato Hagi, Hidetoshi Kawaguchi, Norikazu Masuda, Shigehira Saji, Yutaka Yamamoto, Takahiro Nakayama, Kenjiro Aogi, Keisei Anan, Yoshinori Ito, Shoichiro Ohtani, Nobuaki Sato, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Miki Yamaguchi, Hiroko Yamashita, Toshinari Yamashita, Daisuke Yotsumoto, Satoshi Morita, Masakazu Toi, Shinji Ohno. Outcomes of fulvestrant therapy among Japanese women with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of the JBCRG-C06 safari study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-13.

Background: To evaluate the survival risk is an important factor to decide or treatment options for recurrent breast cancer patients with estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2 negative (HER2−), though there are not enough supporting reports from large-scale databases. The Safari study (UMIN000015168) is a newly conducted retrospective, multicenter cohort study including 1072 ER+ advanced breast cancer Japanese patients treated with fulvestrant 500 mg mostly as a second or later line hormonal therapy. The follow-up data of Safari study is evaluated to focus on any relationship between clinicopathological factors and post-recurrence survival (PRS) in ER+ HER2− recurrent breast cancer patients. Methods: PRS was defined as the duration from the date of initial treatment for recurrent breast cancer to death. The Cox hazards model was used to evaluate the relationship between the clinical factors and PRS. We also performed multivariate analysis on PRS using factors that showed a statistical difference (p < 0.15) in univariate analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) and p-values are described. All tests were two-sided and p Citation Format: Kenjiro Aogi, Hidetoshi Kawaguchi, Norikazu Masuda, Takahiro Nakayama, Keisei Anan, Yoshinori Ito, Shoichiro Ohtani, Nobuaki Sato, Shigehira Saji, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Satoshi Morita, Miki Yamaguchi, Hiroko Yamashita, Toshinari Yamashita, Yutaka Yamamoto, Daisuke Yotsumoto, Masakazu Toi, Shinji Ohno. Factors associated with prolonged post-recurrence survival in patients with postmenopausal estrogen receptor-positive breast cancer taking fulvestrant: A follow-up data of the JBCRG-C06 Safari study factors associated with prolonged post-recurrence survival in patients with postmenopausal estrogen receptor-positive breast cancer taking fulvestrant: A follow-up data of the JBCRG-C06 Safari study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-55.

Background Assessing survival risk is important for discussing treatment options with estrogen receptor-positive (ER+) advanced breast cancer (ABC) patients. However, there are few reports from large-scale databases on the survival risk factors in ER+ ABC. The Safari study (UMIN000015168) was a retrospective, multicenter cohort study involving 1072 Japanese patients receiving fulvestrant 500 mg mostly as a second- or later-line endocrine therapy for ER+ ABC. The follow-up data after the Safari study were examined, focusing on any relationship between clinicopathological factors and overall survival (OS) in ER+ ABC patients. Methods OS in patients with ER+ ABC was analyzed by univariate and multivariate analyses with a Cox proportional hazards model in this study. Results A total of 1031 cases were evaluable for OS analysis. Multivariate analysis showed that younger age ( Conclusions In ER+ ABC patients whose treatment history included fulvestrant, younger age, longer time from ABC diagnosis to fulvestrant use, no prior palliative chemotherapy use, PgR−, and lower histological or nuclear grade correlated positively with prolonged OS.

Applications in which multiple users share the states in real-time over a network have been rapidly spreading, but network latency degrades their quality of service (QoS) and quality of experience (QoE). Although Fog computing effectively mitigates this problem, user allocation methods suitable for these applications with strict latency requirements have not yet been studied. Therefore, this paper proposes both offline and online methods that assume state sharing for user allocation in Fog environments. These methods not only reduce the mean of delays within each group composed of users who share the same states but also guarantee fairness among the users. The simulations demonstrate that our methods complete the allocation in a realistic time and outperform the baseline methods and architectures.

Background The Safari study (UMIN 000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive (ER+) advanced breast cancer (ABC) treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival (OS) after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure (TTF) in patients with ER + ABC. The current study is an ad-hoc analysis that focused on the relationship between the patient factors and OS after recurrence by adding factors generally associated with OS after recurrence. Methods The OS after recurrence in patients with ER + human epidermal growth factor receptor 2 negative (HER2−) recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model. Results A total of 598 cases were used for the analysis of OS after recurrence. Multivariate analysis revealed that favorable OS (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥ 3 years), low nuclear or histological grade (G3 vs. G1), long TTF of initial palliative endocrine therapy (≥ 12 months), and long time to initial palliative chemotherapy (≥ 2 years). Conclusion In patients with ER + HER2 − recurrent breast cancer who received endocrine therapy as the primary palliative treatment, the low proliferation activity of the tumor at the first diagnosis, sensitivity to initial endocrine therapy after the recurrence, and long time to the initiation of chemotherapy might be correlated with the favorable OS after recurrence. Trial registration: University Hospital Medical Information Network: UMIN 000015168, 2014/09/16

Background This study aimed to investigate whether schedule modification is safe and effective in patients intolerant to the standard eribulin dose and schedule. Methods Patients with metastatic breast cancer (MBC) treated with both anthracycline and taxane and ≤ 3 prior regimens of chemotherapy for MBC received eribulin at the standard dose and schedule (1.4 mg/m2 on days 1 and 8 of a 21-day cycle) in the first cycle; change of dosing schedule (1.4 mg/m2 on days 1 and 15 of a 28-day cycle) was determined by change in neutrophil count, platelet count, aspartate aminotransferase, alanine aminotransferase, total bilirubin, serum creatinine, and non-hematological toxicity on day 8 of the first cycle or day 1 of the second cycle. Clinical benefit rate (CBR; primary endpoint), time to treatment failure (TTF), overall survival (OS), and safety were evaluated. Results Of the 88 patients who were enrolled and received standard eribulin therapy in the first cycle, 42 patients were moved to the bi-weekly therapy group and 40 continued standard therapy. In the bi-weekly and standard therapy groups, mean relative dose intensity was 62.7 and 90.9%, CBR was 31.0 and 25.0%, median TTF was 81.5 and 75 days, and OS was 523 and 412 days, respectively. Neither group reported severe adverse events. Conclusion This is the first study to show that a bi-weekly eribulin schedule is tolerable and has comparable efficacy in patients intolerant to the standard eribulin schedule. Clinical trial registration University Hospital Medical Information Network (UMIN) Center (ID: UMIN 000008491). Electronic supplementary material The online version of this article (10.1007/s12282-018-0843-y) contains supplementary material, which is available to authorized users.

Background: Pertuzumab provided overall and progression-free survival (PFS) benefits in HER2-positive metastatic breast cancer patients (pts) in the CLEOPATRA (Clinical evaluation of docetaxel, pertuzumab and trastuzumab) study. However, few studies have described the efficacy of other drugs in combination with pertuzumab plus trastuzumab. Here, we present a pre-specified analysis of eribulin in combination with pertuzumab plus trastuzumab as first- and second-line therapy for advanced or metastatic breast cancer (AMBC) in a multicenter, open-label phase II study (UMIN000012232, JBCRG-M03). Methods: HER2-positive AMBC with no or single prior chemotherapy for AMBC were enrolled. All pts were administered trastuzumab and taxane as adjuvant or first-line chemotherapy. Treatment consisted of eribulin 1.4 mg/m2 on days 1 and 8 of a 21-day cycle and trastuzumab (8 mg/kg loading dose, then 6 mg/kg) plus pertuzumab (840 mg/body loading dose, then 420 mg/ body) once every 3 weeks, all administered intravenously. The primary endpoint was PFS, and secondary endpoints included overall response rate (ORR) and safety. PFS was determined using Kaplan–Meier analysis. Tumor response was assessed according to RECIST ver. 1.1. Results: Fifty pts were enrolled from November 2013 to April 2016. Forty-nine pts were eligible for safety analysis and the full analysis set (FAS) included 46 pts. The median age was 56 years (23–70), and 8 (16%) and 41 (84%) pts were treated in first- and second-line settings, respectively. Eleven pts (23.9%) were de-novo Stage 4, and 35 pts (76.1%) had progressed in metastatic disease after completion of local therapy. Median PFS was 9.3 months (M) (95% confidence interval [CI]: 6.4–12.3). Table 1 shows the efficacy data for each treatment line and includes ORR, complete response rate (CR), partial response rate (PR), stable disease rate (SD), progressive disease rate (PD), not evaluable rate (NE) and PFS in the FAS. The median relative dose intensities of eribulin, trastuzumab, and pertuzumab were 93.3% (77.0%–100%), 100% (96.0%–100%), and 100% (89.7%–100%), respectively, in the FAS. The grade 3/4 adverse events (AE) were neutropenia in 5 pts (10.2%), including 2 pts (4.1%) with febrile neutropenia; hypertension in 3 pts (6.1%), and other AEs in only one patient. The average of the ejection fraction did not decrease significantly. Symptomatic left ventricular systolic dysfunction was not observed. Conclusion: In pts with HER2-positive AMBC, first- and second-line therapy of eribulin in combination with pertuzumab plus trastuzumab demonstrated substantial antitumor activity with an acceptable safety profile. We are planning a phase III study comparing eribulin with taxanes in combination with pertuzumab plus trastuzumab for the treatment of HER2-positive AMBC. Efficacy data for each treatment lineTreatment LineTotal (n=46)First line (n=8)Second line (n=38)PFS (95% CI), months9.3 (6.4-12.3)20.8 (2.8-38.7)8.7 (7.2-10.2)ORR (%)28 (60.9)7 (87.5)21 (55.3)CR (%)8 (17.4)3 (37.5)5 (13.2)PR (%)20 (43.5)4 (50.0)16 (42.1)SD (%)11 (23.9)1 (12.5)10 (26.3)PD (%)5 (10.9)05 (13.2)NE (%)2 (4.3)02 (5.3) Citation Format: Kawaguchi H, Yamashita T, Masuda N, Kitada M, Narui K, Hattori M, Yoshinami T, Matsunami N, Yanagihara K, Kawasoe T, Nagashima T, Bando H, Yano H, Hasegawa Y, Nakamura R, Kashiwaba M, Morita S, Ohno S, Toi M. Phase II study of eribulin in combination with pertuzumab plus trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-07.

The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2-) cases.The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p .001), no prior chemotherapy (p .001), and F500 treatment line (p .001) were correlated with prolonged TTF (median = 5.39 months).In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

In the original publication, the name of the fourth author should be: Takafumi Sangai and his affiliation should be.

Personalised breast cancer therapy requires pathological characterisation of tumours. The proliferative index, based on Ki67, is pivotal, but a standard method has not been established. Here we look for an easy and practical way to evaluate Ki67.Immunohistochemical staining of estrogen receptors, progesterone receptors, HER2 and Ki67 (MIB-1) was performed on resected specimens from 406 primary invasive ductal carcinomas. Ki67 labelling index (LI) from manual counting was compared with visual assessment using a 5-grade scale (Eye-5). Next, 10 pathologists evaluated 100 samples with marked hot spots by using Eye-5. Another 100 samples without marking were also assessed by eight pathologists. One year later, two pathologists reviewed 222 cases with Eye-5. Prognosis was analysed among estrogen receptor-positive cases with postoperative endocrine therapy.Eye-5 showed good correlation to LI. All 136 cases of score 4-5 had LI20% and all 56 cases of score 1 had LI20%, which means that manual counting was not necessary for about half of the cases. Interobserver and intraobserver variability was low even when a hot spot was not fixed. Eye-5 also correlated with histological grade and lymph node metastasis. Combining Eye-5 and histological grade created a new algorism to predict LI, which allows 80% of all cases (74% of luminal cases) without manual counting. Cases of Eye-5 score 1-2 had significantly better survival than score 3-5.Visual assessment of Ki67 by a 5-grade scale (Eye-5) is fast, easy, and reliable with acceptably low interobserver and intraobserver variability. Eye-5 can replace LI in many luminal tumours, and is a strong candidate as a standard method of evaluating Ki67.

Drug cost is considered an important factor in treatment compliance for cancer patients. However, it is difficult to calculate individual drug costs. We were previously unable to provide sufficient information on costs to cancer patients starting drug therapy. Therefore, we developed a tool, in the form of a spreadsheet, which calculates drug costs for breast cancer treatment. This software tool runs on every terminal for electronic medical charts in our hospital. To evaluate the tool, we created 10 fictional breast cancer patient sets. Five pharmacists calculated the drug costs for a single regimen using method A (without software) and method B (with software). The pharmacists then calculated the drug costs for 3 regimens in the same way. We compared the time taken to calculate costs using method A and method B. For the single regimen, the mean time for method B (22.6±6.9 s) was 6.4-times shorter than that for method A (145.2±28.3 s, p0.0001). For the 3 regimens, the mean time for method B (35.5±5.0 s) was 8.9-times shorter than that for method A (315.8±43.1 s, p0.0001). The differences observed were statistically significant. By using the software, we were able to shorten the calculation time for drug costs, and therefore, alleviate the burden on medical staff.

1026 Background: The EMBRACE study established eribulin as a standard treatment for metastatic breast cancer (MBC). However, eribulin at the standard dose and schedule (1.4 mg/m2 on days 1 and 8 ev...

e17797 Background: Drug cost is considered an important factor in the continuation of treatment for cancer patients. However, it is difficult to calculate individual drug cost. We were not able to ...