Cost of Pegfilgrastim for the Prophylaxis of Chemotherapy-induced Febrile Neutropenia in Patients with Breast Cancer Receiving Perioperative Chemotherapy in Daily Practice in Japan: A Posthoc Analysis in a Single-center Retrospective Study.

This study aimed to estimate the medical costs associated with febrile neutropenia (FN) prophylaxis with pegfilgrastim and evaluate its impact on survival outcomes in daily practice in Japan. In this single-center retrospective study, we obtained data from 296 Japanese patients with breast cancer receiving fluorouracil, epirubicin, and cyclophosphamide (FEC)-100 chemotherapy; the patients were divided into the pegfilgrastim and non-pegfilgrastim groups. We analyzed the median costs of chemotherapy, drugs for all adverse events (AEs) and FN, and hospitalization due to FN. We also assessed the survival outcomes. The pegfilgrastim group showed a significantly higher median total cost (JPY 872320.0 vs. JPY 466715.0, p<0.001). This difference was associated with the prophylactic use of pegfilgrastim. The median costs of the drugs for all AE treatments were JPY 9030.4 and JPY 24690.6, with the non-pegfilgrastim group showing a significantly higher cost (p<0.001). In 11 patients hospitalized for FN management, no significant difference in hospitalization cost was observed between the pegfilgrastim and non-pegfilgrastim groups (JPY 512390.0 vs. JPY 307555.0, p=0.102). No significant difference in the 3-year overall survival was observed between the pegfilgrastim and non-pegfilgrastim groups (79.9% vs. 88.3%, p=0.672). In this study, although the total medical cost in daily practice increased because of primary prophylaxis with pegfilgrastim, the 3-year overall survival was not impacted by the use of pegfilgrastim. Our study data suggested that the primary prophylaxis pegfilgrastim should be used during FEC-100 chemotherapy based on the patient-related FN risk factors, instead of routine use.

Status of incremental costs of first-line treatment recommended in Japanese clinical guidelines for metastatic breast cancer patients.

BACKGROUND: The increasing incidence and prevalence of breast cancer alongside diagnostic and treatment technology advances have produced a debate about the financial burden cancer places on the healthcare system and concerns about access. METHODS: This study was conducted at 51 hospitals belonging to the Breast Cancer Study Group of the Japan Clinical Oncology Group using a web-based survey. The survey period conducted from July 2021 to June 2022. The study population included patients with metastatic breast cancer who received the related treatment as their first-line therapy. The proportion of patients who selected that regimen as their first-line treatment was tabulated. The total cost increase for each current standard therapy in comparison to conventional treatments was calculated. RESULTS: A total of 702 patients (pts) were surveyed. Of those enrolled, 342 (48.7%) received high-cost treatment [estimated monthly drug costs exceeding ~500 000 Japanese Yen (JPY)]. Of these, 16 pts (4.7%) were receiving very high-cost treatment, amounting to more than 1 000 000 JPY per month. Fifty three (15.5%) of the patients who received high-cost treatment were 75 years of age or older. Of these, 1 pt (0.3%) were receiving very high-cost treatment. Analyses of incremental costs by current drugs showed that abemaciclib was costly with total additional cost of 6 365 670 JPY per patient. The total additional cost of the regimen per patient that included palbociclib was the second highest at 4011248 JPY, followed by atezolizumab at 3209033 JPY. CONCLUSIONS: The findings indicate that evaluating the financial implications of high-cost treatments requires considering not only drug prices but also analysis of total cost increase.

Comparison of proportions and prognostic impact of pathological complete response between evaluations of representative specimen and total specimen in primary breast cancer after neoadjuvant chemoradiotherapy: an ancillary study of JCOG0306.

BACKGROUND: In JCOG0306 trial, a phase II study to examine the efficacy of neoadjuvant chemotherapy followed by radiation therapy (NAC-RT) to primary breast cancer, pathological complete response (pCR) was evaluated from specimens of the representative cross-section including the tumor center that had been accurately marked [representative specimen (RS) method]. In this ancillary study, we examined if the RS method was comparable to the conventional total specimen (TS) method, which is widely employed in Japan, to identify the pCR group showing excellent prognosis. METHODS: We obtained long-term follow-up data of 103 patients enrolled in JCOG0306 trial. As histological therapeutic effect, pCR (ypT0 and ypT0/is) and quasi-pCR [QpCR, ypT0/is plus Grade 2b (only a few remaining invasive cancer cells)] were evaluated with RS and TS methods. Concordance of pCR between these two methods and associations of the pCR with prognosis were examined. RESULTS: ypT0, ypT0/is, and QpCR were observed in 28 (27.2%), 39 (37.9%), and 45 (43.7%) patients with RS method, whereas these were 20 (19.4%), 25 (24.3%) and 40 (38.9%) with TS method, respectively. Between RS and TS methods, concordance proportions of ypT0 and ypTis were 92.2% and 86.4%, respectively. Risk of recurrence of ypT0/is group was lower than that of non-ypT0/is group (HR 0.408, 95% CI [0.175-0.946], P = 0.037) and risk of death of ypT0/is group was lower than that of non-ypT0/is group (HR 0.251, 95% CI [0.073-0.857], P = 0.027). The ypT0 and ypT0/is groups with RS method showed excellent prognosis similarly with those with TS method, and RS method was able to differentiate the OS and RFS between pCR and non-pCR than TS method significantly even if pCR was classified ypT0 or ypT0/is. With TS method, QpCR criteria stratified patients into the better and worse prognosis groupsmore clearly than pCR criteria of ypT0 or ypT0/is. CONCLUSIONS: RS method was comparable to TS method for the evaluation of pCR in the patients who received NAC-RT to primary breast cancer provided the tumor center was accurately marked. As pCR criteria with RS method, ypT0/is appeared more appropriate than ypT0.

Analysis of Adverse Events Associated with Trastuzumab Deruxtecan in Patients with Gastric and Breast Cancer: A Retrospective Study.

Trastuzumab deruxtecan (T-DXd) has displayed demonstrable efficacy and manageable toxicity in previously treated patients with advanced gastric and breast cancer, and it has been approved in Japan. However, there is a lack of data on the optimal management in clinical practice. Therefore, we assessed the adverse event (AE) profiles of T-DXd in patients with advanced gastric or breast cancer to provide guidance for appropriate management. This retrospective study was conducted at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. We reviewed the medical records of patients with advanced gastric or breast cancer who received T-DXd between May 2020 and December 2021. AEs occurring within the first three cycles of T-DXd were evaluated according to Common Terminology Criteria for Adverse Events version 5.0. Thirty-six patients were enrolled (gastric: n = 19, breast: n = 17). All 15 males had gastric cancer, whereas 4 and 17 females had gastric and breast cancer, respectively. Interstitial lung disease (ILD) occurred in five patients (14%), but no patients had severe ILD. Gastrointestinal (GI) toxicities, including nausea (61%), vomiting (22%), decreased appetite (33%), and diarrhea (39%), were the most common AEs. The incidence of GI toxicities did not differ by cancer type; however, nausea was significantly more common in females (81 vs. 33%; p < 0.01). T-DXd was safely administered in clinical practice in patients with previously treated advanced gastric or breast cancer. The management of GI toxicities is important in the clinical implementation of T-DXd.

Pilot trial of an electronic patient-reported outcome monitoring system in patients with metastatic breast cancer undergoing chemotherapy.

BACKGROUND: Electronic patient-reported outcomes monitoring (ePROM) is a useful communication tool for patients and healthcare providers in cancer chemotherapy. In this study, we examined the feasibility of our newly developed ePROM system, which we refer to as "Hibilog". METHODS: An ePROM app was developed by extracting 18 items from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE). Symptom monitoring was conducted every two weeks for patients with metastatic breast cancer undergoing chemotherapy. The primary outcome was the response rate to the ePROM system. The secondary outcomes were response time, item missing rate, and distribution of responses for each symptom. RESULTS: A total of 71 cases (mean age 52.6 years) were analyzed. Performance status was 0 in 76% of the cases and 1 or higher in 24%. First-line treatment was being administered in 30% of cases, second-line treatment in 17%, and third-line or higher treatment in 53%. The response rate to the ePROM system from registration to week 40 remained high at around 80%, indicating good compliance. The average response time was 5.5 min and the missing rate for each item was below 0.4%. Among 1,093 responses, the top 3 symptoms causing interference with daily life were Fatigue (63%), Numbness and tingling (48%), and General pain (46%). CONCLUSION: Our developed ePROM system was able to capture symptoms accurately in patients with metastatic breast cancer undergoing chemotherapy while maintaining a high response compliance.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

Prognostic impact of adjuvant endocrine therapy for estrogen receptor-positive and HER2-negative T1a/bN0M0 breast cancer.

PURPOSE: Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. METHODS: We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. RESULTS: Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32-0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39-0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). CONCLUSIONS: The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease.

Metastasis-directed therapy for oligometastases in breast cancer.

The concept of oligometastases was first proposed to describe a disease state between localized cancer and extensive metastasis. After the emergence of variations in the definition of oligometastasis, in April 2020 the European Society for Radiotherapy and Oncology and the European Organization for Research and Treatment of Cancer defined oligometastases as the presence of one to five metastatic lesions that can be safely treated. However, the pathogenesis of oligometastases remains unknown, and it is uncertain which patients will benefit from metastasis-directed therapy. Breast cancer with oligometastases is generally managed with systemic therapy. Retrospective studies have suggested that the addition of metastasis-directed therapy, such as surgery, radiofrequency ablation and stereotactic body radiation therapy, may increase overall survival in breast cancer patients with oligometastases, but as yet there have been no prospective studies. Phase II trials of stereotactic body radiation therapy or fractionated irradiation for oligometastases of breast cancer have demonstrated impressive rates of local control and overall survival. Although the efficacy of stereotactic body radiation therapy in the SABR-COMET was largely anticipated, it is noteworthy that only 18% of the patient population had breast cancer. For this reason, various trials were planned or are being conducted globally to investigate the efficacy of metastasis-directed therapy for oligometastases of breast cancer. Metastasis-directed therapy for oligometastases has been shown to be effective, and stereotactic body radiation therapy and other therapies are commonly used internationally and are considered to be safe. However, the efficacy of metastasis-directed therapy for oligometastases has not yet been proven. The results of future clinical trials are thus eagerly awaited.

Mitigation of paclitaxel-induced peripheral neuropathy in breast cancer patients using limb-cooling apparatus: a study protocol for a randomized controlled trial.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common adverse events that can significantly impair the quality of life of patients. Although limb cooling may be beneficial for preventing CIPN, logistical challenges exist in ensuring consistent efficacy and safety. The purpose of this randomized controlled trial is to validate whether limb cooling with strict temperature control can reduce CIPN in patients with breast cancer receiving weekly paclitaxel as a perioperative treatment. Methods: This study is a multicenter, double-blinded, randomized controlled trial. We plan to enroll patients with breast cancer who are scheduled to receive 12 weekly doses of paclitaxel (60 min 80 mg/m2 intravenous infusion) as perioperative chemotherapy. Patients will be randomly divided into the intervention or control groups and undergo limb cooling therapy maintained at a constant temperature of 13°C and 25°C, respectively. The primary endpoint is the proportion of patients who report Patient Neurotoxicity Questionnaire (PNQ) ≥ D in their limbs by the end of the study treatment or at the time of discontinuation. Discussion: The results of this trial will contribute to the establishment of new evidence for limb cooling therapy in the mitigation of CIPN and present a safe and stable cooling device that may be suitable for use in the clinic. Clinical trial registration: https://jrct.niph.go.jp/en-latest-detail/jRCT2032210115, identifier jRCT2032210115.

Factors associated with financial toxicity in patients with breast cancer in Japan: a comparison of patient and physician perspectives.

BACKGROUND: Financial toxicity (FT) is a notable concern for patients with breast cancer worldwide. The situation regarding FT in Japan, however, has not been well explored. This study examined FT in patients with breast cancer in Japan and presented an overview of the group study's overall findings. METHODS: The survey used the Questant application and primarily targeted patients with breast cancer attending research facilities and physicians who are members of the Japanese Breast Cancer Society. The Japanese version of the Comprehensive Score for FT (COST) was used to quantify patients' FT. Multiple regression analysis was used to identify factors related to FT in patients with breast cancer in Japan and evaluate the sufficiency of information support level (ISL) for medical expenses. RESULTS: We collected 1558 responses from patients and 825 from physicians. In terms of factors affecting FT, recent payments had the highest impact, followed by stage, and related departments positively affecting FT. Conversely, factors such as income, age, and family support were found to negatively affect FT. A significant discrepancy was identified between patients and physicians in perceived information support, with patients frequently feeling unsupported and physicians believing that they have provided adequate support. Furthermore, differences in the frequency of explanations and opportunities to ask questions about medical costs across FT grades were found. The analysis also showed that physicians with a better understanding of information support needs and greater knowledge of medical costs tended to provide more support that is comprehensive. CONCLUSION: This study emphasizes the importance of addressing FT in patients with breast cancer in Japan and highlights the need for enhanced information support, deeper understanding by physicians, and collaborative efforts among professionals to mitigate financial burden and provide personalized, tailored support for individual needs.

The impact of obesity and endocrine therapy on the prognosis of premenopausal women with hormone receptor-positive breast cancer: A single-institute retrospective study.

BACKGROUND: Higher body mass index (BMI) is associated with worse prognosis in pre- and postmenopausal patients with breast cancer (BC). However, there is insufficient evidence regarding the optimal adjuvant endocrine therapy for obese premenopausal women with hormone receptor (HR)-positive BC. AIM: To evaluate the impact of obesity and adjuvant endocrine therapy on prognosis in premenopausal patients with BC. METHODS AND RESULTS: We retrospectively reviewed the medical record of premenopausal women who received curative surgery for clinical stage I-III HR-positive BC from 2007 to 2017. Patients were classified into five groups according to BMI: underweight (UW), normal weight (NW), obese 1 degree (OB1), obese 2 degree (OB2), and obese 3 degree (OB3) categories. The primary analysis was a comparison of BC-specific survival (BCSS) according to BMI (UW/NW vs. OB1-3) and adjuvant endocrine therapy (with or without ovarian function suppression [OFS]). Of 13 021 patients, the data of 3380 patients were analyzed. BCSS in OB1-3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40-4.02: p = .0009). In OB1-3 patients who received tamoxifen (TAM), BCSS was significantly worse than that in UW/NW patients (p = .0086); however, a significant difference was not shown in patients who received TAM and OFS (p = .0921). CONCLUSION: High BMI was associated with worse prognosis in premenopausal patients with HR-positive BC who received adjuvant TAM. The role of OFS as adjuvant endocrine therapy remains unclear, and further studies are required to explore the adequate management of obese premenopausal patients.

Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients.

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients' quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001-3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01).

Pertuzumab retreatment for HER2-positive advanced breast cancer: A randomized, open-label phase III study (PRECIOUS).

No standard options existed for human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer that progresses after second-line trastuzumab emtansine therapy before 2020. The purpose of this study was to examine the efficacy of pertuzumab retreatment after disease progression following pertuzumab-containing therapy for HER2-positive locally advanced or metastatic breast cancer for the first time. This randomized, open-label, multicenter phase III trial was undertaken in 93 sites in Japan. Eligible patients with HER2-positive breast cancer who had received pertuzumab, trastuzumab, and chemotherapy as first- and/or second-line therapy were randomly assigned (1:1) to: (i) pertuzumab, trastuzumab, and physician's choice chemotherapy (PTC), or (ii) trastuzumab and physician's choice chemotherapy (TC). The primary end-point was investigator-assessed progression-free survival (PFS). Between August 1, 2015 and December 31, 2018, 219 patients were randomized to PTC (n = 110) or TC (n = 109). Median follow-up was 14.2 months (interquartile range, 9.0-22.2), and median PFS was 5.3 months (95% confidence interval [CI], 4.0-6.6) with PTC and 4.2 months (95% CI, 3.2-4.8) with TC (stratified hazard ratio 0.76 [95% CI upper limit 0.967]; p = 0.022). Progression-free survival was improved by adding pertuzumab in all prespecified subgroups. The PTC arm showed a trend towards better overall survival and duration of response, but similar objective response and health-related quality of life. The incidence of treatment-related adverse events was similar between groups except for diarrhea. Pertuzumab retreatment contributes to disease control for HER2-positive locally advanced or metastatic breast cancer previously treated with pertuzumab-containing regimens.

Assessment of a cancer genomic profile test for patients with metastatic breast cancer.

Comprehensive cancer genomic profile (CGP) tests are being implemented under Japanese universal health insurance system. However, the clinical usefulness of CGP test for breast cancer patients has not been evaluated. Of the 310 patients who underwent CGP testing at our institution between November 2019 and April 2021, 35 patients with metastatic breast cancer whose treatment strategy was discussed by our molecular tumor board within the study period were investigated after exclusion of 2 cases that could not be analyzed. The turn-around time, drug accessibility, and germline identification detection were evaluated. The subtype was luminal in 20 patients (57.1%), triple-negative in 12 patients (34.3%), and luminal-HER2 in 3 patients (8.6%). Actionable gene mutations were detected in 30 patients (85.7%), and 7 patients (20.0%) were recommended for clinical trial participation, with the drug administered to 2 patients (5.7%). Three patients (8.6%) died due to disease progression before the test results were disclosed. We report the results of an initial assessment of the utility of CGP testing for patients with metastatic breast cancer under Japanese universal health insurance system. Conducting CGP tests at a more appropriate time could provide patients with greater benefit from treatments based on their specific gene mutations.

Serial circulating tumor DNA monitoring of CDK4/6 inhibitors response in metastatic breast cancer.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) significantly improve progression-free survival and have become the standard therapy for estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer patients. Treatment surveillance by radiological imaging has some limitations in detection and repeated biopsy genomic profiling is not clinically feasible. Serial circulating tumor DNA (ctDNA) analysis may provide insights into treatment response. Here we performed serial ctDNA analysis (n = 178) on 33 patients. Serial ctDNA analysis identified disease progression with sensitivity of 75% and specificity of 92%. In eight of 12 patients (61%) responding to CDK4/6i who eventually developed progressive disease, serial sampling every 3 or 6 months captured the initial rise of ctDNA with an average lead time of 3 months. In three of eight patients that did not respond to CDK4/6i (progressive disease at first radiological assessment, 3 months), biweekly sequencing within the first cycle of CDK4/6i treatment (1 month) detected sustained ctDNA levels (≥0.2% variant allele frequency), with lead time of 2 months. Serial ctDNA analysis tracked RECIST response, including clinically challenging scenarios (bone metastases or small-sized target lesions), as well as detecting acquired genetic alterations linked to CDK4/6i resistance in the G1 to S transition phase. Circulating tumor DNA analysis was more sensitive than carcinoembryonic antigen or cancer antigen 15-3 serum tumor markers at monitoring tumor response to CDK4/6i treatment. Our findings indicated the possible clinical utility of serial ctDNA analysis for earlier progressive disease detection and real-time monitoring of CDK4/6i response.

Trastuzumab and fulvestrant combination therapy for women with advanced breast cancer positive for hormone receptor and human epidermal growth factor receptor 2: a retrospective single-center study.

BACKGROUND: Trastuzumab and fulvestrant combination therapy is one of the treatment options for patients with hormone receptor- and human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer; however, there are limited studies evaluating the efficacy of this combination therapy. METHODS: We retrospectively reviewed the data of women with hormone receptor- and HER2-positive metastatic breast cancer who received trastuzumab and fulvestrant combination therapy between August 1997 and August 2020 at the Cancer Institute Hospital. The primary endpoint of this study was progression-free survival, and the secondary endpoints were response rate, overall survival and safety. RESULTS: We reviewed the data of 1612 patients with recurrent or metastatic breast cancer, of which 118 patients were diagnosed with hormone receptor- and HER2-positive breast cancer. Of these, 28 patients who received trastuzumab and fulvestrant combination therapy were eligible for this study. The median treatment line for advanced breast cancer was 6 (range, 1-14), the median progression-free survival was 6.4 months (95% confidence interval [CI], 3.46-8.17), and the median overall survival was 35.3 months (95% CI, 20.0-46.7). Of the 28 patients, partial response was observed in 1 (4%), stable disease in 17 (61%), and progressive disease in 10 (36%) patients. The disease control rate was 64%. Adverse events of grade ≥ 3 were not observed. CONCLUSIONS: Trastuzumab and fulvestrant combination therapy showed moderate clinical efficacy and no severe toxicity after standard anti-HER2 treatment, which is a reasonable treatment option for patients with hormone receptor- and HER2-positive metastatic breast cancer. These data contribute to understanding the efficacy of trastuzumab and fulvestrant combination therapy as control data for further development of anti-HER2 agents plus hormone therapy.

Quality of life in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer.

BACKGROUND: To report our findings on quality of life (QoL) in a randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). METHODS: Patients with HER2-negative MBC were randomly assigned to three different doses of q3w nab-PTX (SD 260 mg/m2 vs. MD: 220 mg/m2 vs. LD 180 mg/m2). QoL was assessed at baseline and during the second, fourth and sixth courses of treatment using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), Cancer Fatigue Scale (CFS) and EuroQol 5-Dimension (EQ-5D). Comparisons were performed with mixed-model repeated measures (MMRM). RESULTS: A total of 141 patients were enrolled in the parent study, and 136 (96%) (44, 45 and 47 in the SD, MD, and LD groups) were included in the analysis. MMRM analysis showed that the difference from the baseline FACT-Taxane trial outcome index at MD and LD were significantly higher than that at SD (MD vs. SD P < 0.001, LD vs. SD P < 0.001). Differences from baseline for FACT-Taxane total, physical and emotional well-being, and taxane subscale scores at MD and LD were also higher than at SD. The difference from baseline for the CFS score at LD was lower than at SD (P = 0.013) and those for EQ-5D utility scores at MD and LD were higher than at SD (MD vs. SD P = 0.011, LD vs. SD P < 0.001). CONCLUSION: QoL of patients treated with 220 or 180 mg/m2 of q3w nab-PTX was significantly better than that of patients treated with 260 mg/m2. TRIAL REGISTRATION: The protocol was registered at the website of the University Hospital Medical Information Network (UMIN), Japan (protocol ID: UMIN000015516), on 01/11/2014. Details are available at the following address: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017916.