Pretreated Metastatic Breast Cancer Research Articles

Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer

BackgroundThere is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician’s choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methodsIn this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280mg/m2 intravenously every 3weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). ResultsA total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P=0.67; median 9.1months for vinflunine versus 9.3months for AA), progression-free survival (hazard ratio 0.94, P=0.49; median 2.5 versus 1.9months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P=0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). ConclusionsVinflunine 280mg/m2 q3w did not improve OS compared with the physician’s choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320mg/m2 merits evaluation. ClinicalTrials.govNCT01091168.

414 (PB-047) - Is metronomic cyclophosphamide and methotrexate chemotherapy a useful palliative regimen in patients with heavily pretreated metastatic breast cancer?

414 (PB-047) - Is metronomic cyclophosphamide and methotrexate chemotherapy a useful palliative regimen in patients with heavily pretreated metastatic breast cancer?

Abstract OT3-06-05: A phase Ib/II trial of coPANlisib in combination with tratuzumab in pretreated recurrent or metastatic HER2-positive breast cancer “PantHER”

Abstract Background The phosphoinositide 3 kinase (PI3K) pathway is important in the oncogenic function of HER2. Aberrent activation of PI3K is implicated in resistance to trastuzumab and other HER2-targeted therapies and is frequent, with up to 22% of HER2 positive breast cancer having a PIK3CA mutation. Copanlisib is a pan-class 1 PI3K inhibitor that shows particular activity against PI3Kα, the isoform encoded by the PIK3CA gene. Copanlisib has been shown to re-sensitise trastuzumab resistant cell lines to trastuzumab with synergism seen in some cell lines between copanlisib and HER2 targeted therapy. Trial design The study is a phase Ib/II open label, single arm adaptive, multi-centre trial of copanlisib in combination with trastuzumab. Eligible patients are treated with a dose escalation schedule of copanlisib IV on Days 1, 8 and 15 of a 28 day cycle with trastuzumab 2 mg/kg weekly (loading dose of 4 mg/kg in cycle 1). The phase II dose will be based on the maximum tolerated dose (MTD) established in Phase Ib. Patients are treated until radiologic or symptomatic progression, unacceptable toxicity, consent withdrawal or physician's decision. Eligibility criteria Eligible patients must have recurrent incurable or metastatic HER2-positive breast cancer that has progressed on at least one prior line of trastuzumab or T-DM1-based treatment regimen in this setting. Patients with treated and controlled brain metastases are eligible. Participants must have adequate organ function and ECOG PS ≤ 2. Patients recruited for the Phase II part of the study must have a PIK3CA mutation. Patients with uncontrolled arterial hypertension, uncontrolled diabetes or recent clinically serious infections are excluded. Specific aims The primary end point for the phase Ib part of this study is to determine the MTD for the combination. For the phase II study is anti-tumour efficacy, measured by Clinical Benefit Rate (CBR). Secondary end points are evaluation of safety and tolerability, progression-free survival, time to treatment failure, duration of response and overall survival. Incorporated translational endpoints include examination of molecular tumor adaptation in tissue and blood. Given the role of PI3K in cellular glucose metabolism, an additional exploratory objective is to determine if quantitive reduction in metabolic signal on Positron Emission Tomography-Computed Tomography (PET-CT) is predictive of benefit from therapy. Statistical methods To establish the MTD, we use a modified 3+3 design where 3 additional patients will be accrued even if the first 3 patients accrued experience no dose limiting toxicities (DLT) in sequential cohorts for a planned 12 patients. To determine the CBR, a one sample exact binomial test with a one sided significance level of 5%, 19 evaluable patients will provide >80% power to detect a difference between the null hypothesis proportion of 30% for CBR versus the alternative hypothesis proportion of 65%. Present accrual and target accrual There are 9 patients recruited so far to the phase Ib part of this study. Target accrual is 12 and for phase II is 19 patients. Contact information for people with a specific interest in the trial Prof Bryan Hennessy, Beaumont Hospital, Dublin Ireland Funded by Bayer Citation Format: Keegan NM, Walshe J, Gullo G, Kennedy J, Bulger K, Kelly CM, Crown J, Toomey S, Egan K, Kerr J, Given M, Hernando A, Teiserskiene A, Grogan L, Breathnach O, Morris PG, Keane M, Hennessy BT. A phase Ib/II trial of coPANlisib in combination with tratuzumab in pretreated recurrent or metastatic HER2-positive breast cancer “PantHER” [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 OT3-06-05.

Abstract P5-21-22: Palbociclib in highly pretreated metastatic ER-positive HER-2 negative breast cancer

Abstract Palbociclib, a first-in-class CDK 4/6 inhibitor, in combination with letrozole or fulvestrant is now licensed for the first or second line treatment of postmenopausal women with hormone-sensitive HER-2 negative metastatic breast cancer (MBC), but its activity in later lines is unknown. In Belgium, a compassionate Use Program (CUP) was temporarily established to provide palbociclib after at least 4 lines of systemic treatment for MBC. The UZ Leuven Multidisciplinary Breast Center included 82 patients in this CUP from September 28th 2015 to March 14th 2017. This analysis describes retrospectively collected efficacy (Revised RECIST guideline, version 1.1) and safety data from 68 patients with at least 6 months follow-up at the data cut-off point. The primary endpoint was clinical benefit, defined as being on treatment for at least 6 months (CR + PR + SD). Most of the patients (89.7%) used palbociclib in combination with letrozole. Other combinations are with tamoxifen (2.9%), fulvestrant (2.9%), exemestane (1.5%), anastrazole (1.5%) and megestrol (1.5%). At the data cut-off point, 18 patients are still on-treatment with palbociclib. The average duration of treatment is 5.7 months [range 2m- 17m]. The mean age of the patients was 66.3 years [range 34.8y – 85.9y] at the time of inclusion. Patients had had an average of 5.7 lines of systemic therapy [range 4 – 11 lines] before starting palbociclib, which was in 61.8% at least one line of chemotherapy. In this highly pretreated setting, 29 patients experienced stable disease lasting ≥ 6 months, resulting in an overall clinical benefit rate of 42.6%. 19.1% (13/68) showed stable disease for ≥ 9 months and 8% for ≥ 12 months. The subjective tolerance of the combination treatment was good, with 38% (26/68) of the patients discontinuing or delaying treatment following adverse events which were in the vast majority hematologic but asymptomatic. No factors predicting clinical benefit could be identified: use of chemotherapy before starting Palbociclib (p = 0.4644), age (p = 0.7029), time between primary breast cancer diagnosis and starting palbociclib (p = 0.1919) or time between first metastasis and starting palbociclib (p = 0.1108) and bone-only disease (p = 1,0000) were not significantly associated with clinical benefit at 6 months. These data not only support the findings of the PALOMA studies, but also show unexpectedly high clinical benefit and safety of palbociclib in heavily pretreated endocrine-resistant hormone receptor positive HER-2 negative advanced breast cancer. An update of these data will be presented. Citation Format: Hoste G, Punie K, Wildiers H, Neven P, Berteloot P, Van Nieuwenhuysen E, Han S, Concin N, Salihi R, Lefever I, Vergote I. Palbociclib in highly pretreated metastatic ER-positive HER-2 negative 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 P5-21-22.

Trastuzumab Emtansine: Antibody-drug Conjugate in Treatment of Human Epidermal Growth Factor Receptor-2-Positive Metastatic Breast Cancer

AbstractThe human epidermal growth factor receptor-2 (HER2)-targeted therapies have improved clinical outcomes for patients at any stage of HER2-positive breast cancer (BC). Trastuzumab, a monoclonal antibody that targets the HER2 receptor on BC cells, showed improved survival in metastatic BC (MBC). However, resistance to therapy arises in the majority of patients with advanced disease. Antibody–drug conjugate (ADC) is a relatively new development to deliver cytotoxic drugs specifically to cancer cells. Trastuzumab emtansine (T-DM1) is a HER2-targeted ADC, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent, emtansine (DM1, derivative of maytansine). T-DM1 has been approved for use in patients with MBC who have failed prior therapy with trastuzumab and a taxane. Dose finding Phase I study established the maximum tolerated dose at 3.6 mg/kg every 3 weeks. Phase I and II studies of T-DM1 have shown clinical activity and a favorable safety profile in HER2-positive MBC patients. The Phase III randomized EMILIA and TR3RESA trials demonstrated that T-DM1 significantly improves progression-free and overall survival in pretreated HER2-positive MBC patients. Nausea and fatigue are most commonly reported adverse drug reactions with T-DM1 and cardiac toxicity comparable with standard of care therapies. The drug is well tolerated in most patients, with a predictable pharmacokinetic profile and minimal systemic exposure to free cytotoxic DM1. T-DM1 has emerged as an effective therapeutic option for the management of patients with HER2-positive MBC.

Combination of pegylated liposomal doxorubicin plus gemcitabine in heavily pretreated metastatic breast cancer patients: Long-term results from a single institution experience.

The combination of Pegylated Liposomal Doxorubicin (PLD) plus Gemcitabine (GEM) has been previously investigated in the treatment of metastatic breast cancer (MBC). PLD is a doxorubicin formulation with prolonged circulation time and better tissue distribution. GEM is a nucleoside analog with nonoverlapping toxicity compared to PLD. The aim of our study was to assess efficacy, toxicity, and long-term outcome of this combination. Patients with heavily treated MBC were retrospectively analyzed. Chemotherapy consisted of PLD 25mg/m2 and GEM 800mg/m2 day 1, on a three-week schedule. Cardiac function was evaluated baseline and during treatment. Radiological response was graded according to RECIST criteria v1.1. Toxicity was scored according to CTCAE v4.0. Progression-free survival (PFS) and overall survival (OS) were evaluated. From 2001 to 2014, 122 pts were included. Median age was 55 (range: 28-84). Median previous treatment schedules in the metastatic scenario were 3 (range: 1-15). Most patients received prior anthracyclines (85%). Median number of metastatic sites was 2 (range: 1-7). Median number of cycles delivered was 5 (range: 1-36). Overall response rate was 31% (5% complete responses; 26% partial responses). Stable and progressive diseases were observed in 32% and 26% of patients. Grade ≥3 neutropenia was observed in 29 patients (24%). Grade ≥3 hand-foot syndrome was detected in 17 patients (14%), mostly since cycle 3 (88%). Median cumulative PLD dose was 125mg/m2 . At a median follow-up of 101months, median PFS and OS were 7 and 22months, respectively. PLD-GEM combination achieves remarkable long-term outcomes with an acceptable toxicity profile in patients with MBC.

P1-013 - Eribulin efficacy for metastatic breast cancer amongst the real-world treatment pattern

Treatments options for metastatic breast cancer (MBC) have become more efficacious and numerous. Eribulin is an active agent for MBC treatment, but the effective usage of this drug is still unclear. Although the usage of eribulin for MBC in Europe is limited to patients who exposed to minimum of two previous chemotherapy regimens including anthracyclines and taxanes in the adjuvant or metastatic setting, there is no such strict limitation in Japan. The purpose of this retrospective study is to evaluate effective usage of erubulin in pretreated metastatic breast cancer patients in daily practice. Chart review was done for the patients who underwent chemotherapy, which include at least paclitaxel or eribulin for metastatic breast cancer between October 2012 and April 2016 in our single institute. One hundred and fifty patients were included in our cohort. The primary efficacy measure assessed overall survival (OS). Among human epidermal growth factor receptor 2 (HER2) negative patients, 51 received eribulin (eribulin group) and 66 received conventional chemotherapy excluding erubulin (non-eribulin group). The median OS from MBC diagnosis in the eribulin group was 39.0 months compared with 22.7 months in the non-eribulin group [hazard ratio (HR): 0.46, 95%CI 0.29-0.73; p = 0.001]. Eribulin seemed to have significant survival benefit in patients with lung metastasis, but not in patients without lung metastasis in our cohort. Same trend was recognized with liver metastasis, or bone metastasis. Eribulin therapy may have a survival benefit in Japanese women with HER2 negative MBC. And may have benefit in MBC patients with lung, liver or bone metastasis.

Oral etoposide in heavily pretreated metastatic breast cancer: a retrospective analysis of efficacy and safety

Oral etoposide in heavily pretreated metastatic breast cancer: a retrospective analysis of efficacy and safety

Eribulin mesylate in advanced breast cancer: retrospective review of a single institution experience

Purpose: Eribulin is a non-taxane microtubule inhibitor, which can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of eribulin monotherapy in heavily pretreated MBC patients. Materials and methods: This was a single institution retrospective analysis of MBC patients treated with eribulin from August 2012 to May 2016. These patients had received at least 2 lines of prior therapy for metastatic disease. Patients received standard doses of eribulin and were monitored for responses. Results: Forty-four patients were included in this analysis who received at least one cycle of eribulin were identified. Median patient age was 58 years (range 43-76). All were pretreated with anthracyclines and taxanes and 72% with capecitabine. Brain metastases were present in 9 (20%) patients at the time of initial eribulin administration. Most patients were heavily pretreated with a median of 3 (range 2-7) previous chemotherapy lines prior to eribulin and had significant visceral involvement (median 3 organs). A median of 5 cycles of eribulin was delivered. There were no complete responses; partial responses were 20% (9/44) with a 54,5% of disease control rate (25/44), progressive disease was seen on eribulin in 44,5% (19/44) patients. The median progression-free survival was 4.5 months (95% CI 2.8- 6,2) and median overall survival was 12 months (95% CI 7.8-16.4). Only one patient experienced grade 3 neurotoxicity. Three patients (6,8%) stopped eribulin due to fatigue grade 3. No hypersensitivity reactions and no toxic deaths were observed. Conclusion: Eribulin monotherapy is an effective and safe regimen for MBC patients. In our experience, eribulin maintains its activity out of clinical trials, without unexpected toxicities.

Apatinib for metastatic breast cancer in non-clinical trial setting: Satisfying efficacy regardless of previous anti-angiogenic treatment.

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2. This study aimed to evaluate the efficacy and safety of apatinib in metastatic breast cancer (MBC) under non-clinical trial setting, and to study the impact of previous antiangiogenic treatment to the efficacy of apatinib. 52 MBC patients treated with apatinib under non-clinical trial setting in Fudan University Shanghai Cancer Center between January 1st 2015 and October 1st 2016 were included. All patients were included in time-to-treatment failure (TTF) analysis, while 45 patients were enrolled for progression-free survival (PFS) and overall survival (OS) analysis because 7 of the patients with treatment discontinuation due to intolerable toxicities had too short time for efficacy assessment. Impact of previous exposure to antiangiogenic treatment and other factors to patients' survival were analyzed by Log-rank analysis and Cox multivariate analysis. The median PFS, median OS, and median TTF were 4.90 (95% confidence interval [CI] 3.44 - 6.36), 10.3 (unable to calculate 95% CI), and 3.93 (95% CI 1.96 - 5.90) months, respectively. Previous treatment of bevacizumab did not affect the efficacy of apatinib. Previous exposure to anthracycline, age of 60 years or older and palmar-plantar erythrodysesthesia syndrome were independent predictors for prolonged PFS. Discontinuation of treatment was more common in age group of 60 years or older than that in younger group, although the difference was not significant. Although toxicities were generally managable, a previously unrecorded grade 3~4 adverse event of dyspnea has been observed. This study confirmed the encouraging efficacy and manageable safety of apatinib on pretreated MBC patients in non-clinical trial setting. For the first time to our knowledge, this study found that previous treatment of bevacizumab did not affect the efficacy of apatinib, and reported an undocumented severe adverse effect of dyspnea.

A phase 2 study of napabucasin with weekly paclitaxel in previously treated metastatic breast cancer.

1084 Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Napabucasin has shown potent synergistic preclinical anti-tumor activity with paclitaxel (PTX). In a phase Ib dose escalation study in patients (pts) with advanced solid tumors, Napabucasin plus weekly paclitaxel was well tolerated. A phase II expansion cohort was opened for pts with previously treated metastatic breast cancer (MBC). Methods: Pts with metastatic MBC for whom weekly PTX was a reasonable treatment option received Napabucasin 240, 480, or 500 mg orally, twice daily in combination with paclitaxel 80 mg/m2 IV weekly on 3 of every 4 weeks. Adverse events were evaluated using CTCAE v4.03 and objective tumor assessments were obtained every 8 weeks per RECIST 1.1 criteria. Results: A total of 50 pts were enrolled including 34 with triple-negative disease (negative for estrogen receptor [ER], progesterone receptor [PR], and Her2 and no prior history of positive receptor status). There were 9 pts positive for ER, PR, or Her2 and refractory to targeted agents, and 7 pts with conversion to triple-negative disease from pathology previously positive for ER, PR or Her2. Pts were heavily pre-treated, having received a median of 5 prior lines of systemic therapy. All but 3 patients had received previous systemic treatment with a taxane. Napabucasin + PTX was well tolerated. Grade 3 AE occurring in ≥ 5% patients was diarrhea (n = 4), and 1 pt had grade 4 diarrhea. The objective response rate (ORR), disease control rate (DCR), median progression free survival (mPFS), and median overall survival (mOS) for all pts and for each sub-group are summarized in the table. Conclusions: Napabucasin (BBI-608) plus weekly paclitaxel has demonstrated safety, tolerability, and encouraging signs of anti-cancer activity in pts with pretreated metastatic breast cancer. Further clinical evaluation of this combination regimen in controlled trials is warranted. Clinical trial information: NCT01325441. [Table: see text]

Multicenter study of the evaluation of eribulin (E) use in Sicily in metastatic breast cancer (MBC): A prospective registry (VESPRY trial).

e12565 Background: Eribulin Mesylate is a non taxane microtubule dynamics inhibitor, approved for heavily-pretreated MBC patients (pts). Methods: This is a multicenter, prospective, single arm study for E-treatment of third line in pretreated MBC pts, conducted in 14 oncology centers in Sicily. All pts had received two previous chemotherapy regimens for MBC. Pts received E at 1.23 mg/m2 on days 1,8 every 3 weeks until progression. Primary Endpoints: overall response rate (ORR) according to the site of metastases and safety. Secondary objectives: Progression-free survival (PFS) and ORR according to different subtypes. PFS curve was estimated using the Kaplan-Meier method. Multivariable logistic regression model were used to evaluate the associations of each variables with tumor response. ORR was assessed according to RECIST 1.1 and safety with CTCAE v4.0. Results: 122 pts were enrolled and received at least 1 dose of E. Median age was 58 (range 29-79). All received previously anthracycline and taxane based-therapies. Subtypes: Luminal A 69%, Luminal B 7%, HER2 enriched 4% and Triple Negative 20%. The most common metastatic sites were bone and liver; 67% had metastatic disease involving two or more organs. A median of 5 cycles of E (range 1-26) was administrated. 106/122 pts were evaluable for efficacy, all for safety. ORR was 48%. Exploratory subset analysis showed significantly higher ORR in the lung, liver and bone lesions compared to other site of metastases and in HER2 negative pts. Multivariable regression model showed that HER2 positive subtype was correlated with a poor response (odd ratio 6.7, 95% CI 1.2-36.5). The median PFS was 14.7 months (mos) (95% CI 7.2–25.7). Among pts with < 65 and ≥ 65 years, the median PFS was 14.7 and 25.7 mos, respectively. Most common toxicities: G2 diarrhea 1%, asthenia G1 4%, G2 neutropenia 6%, G1 neurotoxicity 5%, QT prolongation 1%, G4 mucositis in only one case. Conclusions: This study showed a significant improved of PFS with E in third line setting and a favorable safety profile compared with results reported in the pivotal trial. Our findings suggest that E has substantial antitumor activity when used early for the treatment for MBC with acceptable safety.

First-in-human phase 1/2 study of MCLA-128, a full length IgG1 bispecific antibody targeting HER2 and HER3: Final phase 1 data and preliminary activity in HER2+ metastatic breast cancer (MBC).

2522 Background: MCLA-128 is a novel IgG1 bispecific antibody with enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity targeting HER2 and HER3 receptors. We report final phase 1 single agent escalation data, and safety and preliminary activity at the recommended phase 2 dose (RP2D). Methods: In the phase 1 part, patients (pts) with advanced solid tumors received MCLA-128 every 3 weeks (q3w) IV over 1-2 hr from 40 to 900 mg. In the phase 2 part, pts with selected metastatic indications were treated at the RP2D. Antitumor activity was assessed as per RECIST 1.1. Clinical benefit rate (CBR) was defined as CR + PR + SD ≥12 weeks. Results: As of January 2017, 28 advanced solid tumor pts were treated in the escalation part. No dose limiting toxicities were seen. The RP2D was established as 750 mg q3w (flat dose, corticosteroid premedication) based on safety and PK data. Fifteen pts with HER2 amplified tumors were treated at the RP2D (8 MBC, 4 gastric, 2 ovarian, 1 colorectal). Median age was 52 years (range 33-71), ECOG PS 0/1: 3/12, all ≥2 metastatic sites. The safety profile at the RP2D confirmed dose escalation data; the most common AEs were infusion related reactions in 6 pts (40%; G1-2 in 5 pts, G4 in 1 pt), and G1-2 diarrhea, rash, fatigue in 2 pts each (13%). No congestive heart failure or significant LVEF decreases occurred. The 8 MBC pts had a median 5.5 prior lines of metastatic therapy (range 4-14), all had progressed on 3 prior Her2 inhibitor therapies and received a median of 4.5 MCLA-128 cycles (range 2-12); 1 had a confirmed PR, 5 had SD (including 2 sustained, 11 and 12 cycles). SD was also seen in 2 evaluable MBC pts treated at 480 mg in the phase 1 part (7 and 4 cycles). Overall, CBR in these 10 MBC pts was 70%. Evaluation of other indications is ongoing. Conclusions: MCLA-128 showed a well tolerated safety profile. Consistent antitumor activity was seen in heavily pretreated MBC patients progressing on HER2 therapies. Further exploration of MCLA-128 based combinations with chemotherapy or trastuzumab in less pretreated MBC patients progressing after ≥2 prior Her2 inhibitors including TDM-1 is planned. Clinical trial information: NCT02912949.

Efficacy and Toxicity of Metronomic Chemotherapy in Metastatic Breast Cancer: Egyptian Experience

BackgroundMetronomic chemotherapy (MC) has shown efficacy in patients with metastatic breast cancer (MBC). We therefore tested the efficacy and toxicity of MC in pretreated MBC. Patients and MethodsThis prospective phase II study included 50 patients with heavily pretreated MBC who received MC in the form of continuous oral cyclophosphamide 50 mg/day and oral methotrexate 2.5 mg twice per day on days 1 and 2 every week. The primary end point was progression-free survival (PFS), whereas the secondary end points were response rate, overall survival (OS), and safety. ResultsForty-eight patients were assessed. One patient achieved complete response and 10 patients had partial response, whereas 19 patients had stable disease. The median PFS was 5 months, whereas the median OS was 7 months. Patients with negative progesterone receptors, Eastern Cooperative Oncology Group performance status (PS) 1, achieving response, and those who developed leucopenia, neutropenia, and anemia had significant prolonged PFS, whereas patients with early stage at presentation, receiving < 5 previous treatment lines, achieving response, and experiencing anemia with MC had significant superior OS. In multivariate analysis, achieving response, PS 1, a longer time interval from initial diagnosis until starting MC, and anemia were independent prognostic factors for longer PFS. Initial stage at presentation, number of previous treatment lines, and response were independent prognostic factors for OS. ConclusionsMC is an attractive treatment approach that is effective and less toxic. There are certain groups of patients who seem to benefit more, especially those who experienced toxicity with treatment. Larger trials are warranted to assess this approach early in the course of the disease and with other more active agents.

Eribulin efficacy based on type of metastatic site: a real-life study in heavily pretreated metastatic breast cancer.

The halichondrin B analog, eribulin, exerts an anticancer effect, as reported by several clinical and real-life studies on metastatic breast cancer patients. Here, we evaluated efficacy and safety of eribulin, focusing on response to treatment per metastasis type. This monocentric, real-life study was conducted on 31 heavily pretreated patients with metastatic breast cancer. The median progression-free survival and overall survival were 2.0 and 5.5 months, respectively. All patients (12.9%) responding to eribulin were treated in fourth-line setting. Considering response per metastasis type, bone lesions (13.6%) responded more frequently than other metastases to eribulin. Eribulin exhibited a good overall response rate, with the highest response observed for bone metastases.

Eribulin long-term response and rechallenge: report of two clinical cases

The antimitotic agent eribulin, a synthetic analog of halichondrin B isolated from a marine sponge, resulted particularly effective in improving the overall survival of heavily pretreated metastatic breast cancer (MBC) patients in randomized Phase III clinical trials and real-life studies. However, only scant information is available on the clinical experiences of patients who underwent long-lasting eribulin treatment followed by a rechallenge. Here we presented two cases of MBC women previously treated with several lines of chemotherapy and hormonal therapies, who underwent long-lasting treatment and rechallenge with eribulin, showing a partial response in both periods. These anecdotal experiences suggest that rechallenge with eribulin could represent a treatment strategy for advanced MBC and it should be evaluated in a larger study.

Higher antitumor activity of trabectedin in germline BRCA2 carriers with advanced breast cancer as compared to BRCA1 carriers: A subset analysis of a dedicated phase II trial

Specific alkylators may allow synthetic lethality among patients with germline BRCA1/2-mutations related cancers. The tetrahydroisoquinolone trabectedin administered at 1.3 mg/m2 as a 3-h intravenous infusion every 3 weeks showed activity in patients with pretreated metastatic breast cancer (MBC) and BRCA germline mutations, but mainly in BRCA2 carriers. Data from a phase II study were retrospectively analyzed to compare the efficacy and safety of this trabectedin dose and schedule in pretreated MBC patients bearing germline BRCA1/2 mutations. The primary efficacy endpoint was the objective response rate (ORR) as per Response Evaluation Criteria In Solid Tumors (RECIST) by independent expert review. Duration of response (DR) and progression-free survival (PFS) were secondary efficacy endpoints. Safety was evaluated using the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Data from 26 BRCA1-mutated and 13 BRCA2-mutated patients were analyzed. 69% of BRCA1-mutated cancers were triple-negative vs. 31% of BRCA2-mutated ones. 77% of BRCA1 and 31% of BRCA2 carriers were platinum-pretreated. The ORR in BRCA2-mutated patients was higher than in BRCA1-mutated patients (33.3% vs. 9.1%). DR ranged for 1.4–6.8 months in BRCA2-mutated patients and for 1.5–1.7 months in BRCA1-mutated patients. More BRCA2-mutated patients had disease stabilization for ≥4 months (25.0% vs. 9.1%) and their median PFS was longer (4.7 vs. 2.5 months). Trabectedin was well tolerated in both patient subtypes. In conclusion, trabectedin showed higher antitumor activity in relapsed MBC patients with germline BRCA2 mutations than in those with BRCA1 mutations.

Efficacy and safety of eribulin in taxane-refractory patients in the 'real world'.

Recent clinical, randomized and observational studies showed that eribulin, an analogous of Halichondrin B, was beneficial and well-tolerated in heavily pretreated metastatic breast cancer patients. Here, we aim to evaluate the effectiveness and safety of eribulin in taxane-refractory metastatic breast cancer patients. In this subanalysis of the ESEMPIO study database, we selected 91 subjects with well-defined taxane refractoriness and complete data available. 41 patients (45.2%) showed clinical benefit; one complete response (2.2%) and 16 partial responses (17.6%) were observed. Median progression-free survival and median overall survival were 3.1 and 11.6 months, respectively. The most experienced adverse event was asthenia/fatigue (58%), followed by neutropenia (30%). The treatment-related toxicity led to eribulin-dose reduction in 19 patients and suspension in nine. This study shows that eribulin is effective and well tolerated also in taxane-refractory patients in clinical practice.

Capecitabine and cisplatin (XP) combination systemic chemotherapy in heavily pre-treated HER2 negative metastatic breast cancer.

Purpose/Objective(s)After taxane and anthracycline failure, no standard chemotherapy regimen is established in metastatic breast cancer (MBC). Capecitabine and cisplatin (XP) combination shows promising results in gastrointestinal cancer, but there are relatively scarce data in MBC. We reviewed the clinical outcome of XP regimen in anthracycline and taxane resistant, heavily pretreated MBC patients.Materials/MethodsBetween Jan. 2010 to Feb. 2016, 48 HER2 negative MBC patients who failed anthracycline and taxane based chemotherapy were enrolled. In 43.8% of patients, more than 4 regimens were administrated before XP. Thirty-four patients (70.8%) were hormone receptor (HR) positive MBC. Patients were treated with XP (capecitabine [2000mg/m2 per oral; day 1–14] plus cisplatin [60mg/m2 IV; day 1], every 3 weeks) regimen.ResultsMedian progression-free survival (PFS) in total population was 4.33 months (range 1.1~33.57 months). HR positive patients showed trends for superior PFS compared to triple negative breast cancer (TNBC), without statistical significance (6.53 vs. 3.83 months, P = 0.168). In HR positive group, patients receiving 3 or less lines of chemotherapy showed superior PFS compared to others (10.1 vs. 3.0 months, P = 0.039). In multivariate analysis, HR positive patients receiving 3 or less lines of regimens still showed superior PFS (HR = 2.624, 95% CI; 1.071~6.43, P = 0.032). Most common toxicity was grade 3–4 neutropenia, without treatment-related deaths.ConclusionsXP combination regimen showed clinical benefit with tolerable toxicity in heavily pretreated patients, including HR positive patients. After anthracycline and taxane failure, early administration of XP regimen in selected patients may have improve clinical outcome in breast cancer.

Abstract P5-15-14: Metronomic capecitabine in heavily pretreated metastatic triple negative breast cancer

Abstract This abstract was not presented at the symposium.