Impact of body mass index on overall survival in patients with metastatic breast cancer

BackgroundHigh Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC).MethodsThe National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers.ResultsOf 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m² (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect.ConclusionOverweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor.     

Metastasectomy versus radiation of secondary sites in stage IV breast cancer: Analysis from a national cancer registry

PurposeLocoregional therapy at primary or secondary sites in breast cancer may be associated with improved survival as compared to systemic therapy alone. We explored the sociodemographic and clinicopathologic factors associated with the use of radiation versus surgical resection of metastatic sites (metastasectomy) in patients with de novo stage IV breast cancer, followed by the associated overall survival.MethodsWe sampled the National Cancer Database for patients with de novo stage IV breast cancer, (2010–2017) and described cohort's characteristics using univariate analyses. We identified 5 subgroups based on malignant site involvement: 1. Bone only, 2. Brain only, 3. Liver only, 4. Lung only, and 5. Metastasis involving >1 site. Kaplan-Meier modeling with log-rank testing and multivariate Cox Regression analysis were used to explore differences in overall survival between those that received radiation at secondary sites and those that underwent metastasectomy.ResultsN = 22,749patients were included in this analysis. Radiation (81.2%) was used more commonly than metastasectomy (28.8%). Metastasectomy was associated with better median overall survival across all 5 cohorts (p < .001), with the survival benefit being the most pronounced with lung only (OS: 56.9 months; HR 0.8, 95% CI 0.7–0.9, p = .032), or liver only (OS: 41.6 months; HR: 0.9; 95% CI: 0.7–1.1, p < .001) metastasis.ConclusionMetastasectomy in patients with de novo stage IV breast cancer may be associated with improved overall survival as compared to radiation of secondary lesions, particularly in those with only liver or lung involvement. Prospective randomized controlled trials investigating surgical resection of metastatic sites in patients with breast cancer are warranted.     

Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era

BackgroundTrastuzumab is associated with improvements in overall survival (OS) among patients with HER2-positive metastatic breast cancer (MBC); however disease course and patterns of care in individual patients are highly variable.Methods113 HER2-positive patients diagnosed with MBC from 1999 to 2005 who received trastuzumab-based therapy were retrospectively identified to allow for a minimum of 5 years of follow-up time. Median OS and median duration of therapy were determined using Kaplan–Meier methodology and group comparisons were based on the log-rank test. Hazard ratios (HR) were obtained using a Cox proportional hazards model.ResultsMedian OS was 3.5 years (95% CI 3.0–4.4) from time of initiation of first therapy in the metastatic setting. On univariate analysis, central nervous system (CNS) disease at first recurrence was associated with a shorter OS compared with liver and/or lung metastases or other sites (CNS: 1.9 years CI 0.1–5.9, liver/lung: 3.2 years CI 2.5–4.2, other: 4.6 years CI 2.7–8.0; p = 0.05), however, this was not predictive of survival outcome in multivariate analysis. CNS metastases developed in 62 (55%) patients by the time of death or last follow-up. Median duration of therapy was similar up to 6 lines of treatment, and ranged from 5.2 months to 7.2 months.ConclusionsThe natural history of HER2-positive MBC has evolved with trastuzumab-based therapy with median OS now exceeding 3 years. CNS disease is a major problem with continued risk of CNS progression over time. Patients demonstrate clinical benefit to multiple lines of HER2-directed therapy.     

Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis

BackgroundLocoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs).MethodsRCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted.ResultsAnalyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72–1.29, p = 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14–0.95, p = 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65–1.43), triple negative (HR 1.4, 95% CI 0.50–3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68–1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58–1.62) and in visceral disease (HR = 1.02, 95% CI 0.77–1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result.ConclusionsLRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.     

Men and women show similar survival outcome in stage IV breast cancer

PurposeTo evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC).MethodsPatients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS).ResultsA total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50–69 years and with estrogen receptor–positive disease.ConclusionsThere was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders.     

Real world initial palliative treatment patterns and clinical outcomes in premenopausal patients with hormone receptor-positive,HER2-negative metastatic breast cancer: A study of the National Cancer Center,China

BackgroundTo observe whether guideline non-adherence in initial palliative treatment choices for premenopausal hormone receptor-positive (HR+), HER2-negative metastatic breast cancer (MBC) patients result in worse clinical outcomes in the Chinese population.MethodsThe China National Cancer Center database was used to identify 2194 patients diagnosed between 2004 and 2015. A total of 451 premenopausal patients with HR + HER2- MBC were included. Clinicopathological features and survival information were extracted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared using log-rank test.ResultsThe number of patients receiving initial chemotherapy, endocrine therapy and chemo-endocrine therapy were 222 (49.2%), 80 (17.7%), and 149 (33.0%), respectively. Patients receiving initial chemotherapy were more likely to be luminal B subtype, had more de novo stage IV disease and more liver metastasis, compared with patients receiving initial endocrine therapy. Both PFS and OS were significantly longer for chemo-endocrine therapy group (median PFS 18.9 months and OS 75.0 months), than for endocrine therapy group (median PFS 11.7 months and OS 53.5 months), and chemotherapy group (median PFS 7.1 months and OS 43.9 months). In multivariate analysis, none of the three treatment strategies were independently associated with PFS or OS.ConclusionIn real world, a high percentage of premenopausal patients with HR + HER2- disease received chemotherapy as initial palliative treatment in China, which was not associated with worsened survival. Further studies with larger sample size across China are needed to explore the relationship between this guideline non-adherence and clinical outcomes.     

A randomized phase II trial of trastuzumab plus capecitabine versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxanes: WJOG6110B/ELTOP

BackgroundFor human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies.Patients and methodsWomen with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA.ResultsEighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55–1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26–1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX.ConclusionIn women with HER2-positive MBC previously treated with trastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX.Trial registration numberUMIN000005219.     

Comparison of outcomes between metaplastic and triple-negative breast cancer patients

PurposeMetaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC.MethodsThe National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS.ResultsAltogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p < 0.001). The greater observed OS for patients with TNBC persisted when controlling for stage and when comparing propensity score matched cohorts. On Cox regression, lower age, T1 status, N0 status, chemotherapy, TNBC disease, and radiation therapy (RT) were associated with improved OS.ConclusionsMBC had an association with poorer OS compared to TNBC, while RT and chemotherapy receipt were associated with improved OS for patients regardless of stage. Further studies are needed to corroborate the conclusions herein.     

Effects of locoregional radiotherapy in patients with metastatic breast cancer

ObjectivesThis study aims to assess the clinical outcomes of patients with metastatic breast cancer (MBC) who underwent local radiation therapy (RT) for the primary site.Material and methodsBetween 2005 and 2013, we retrospectively evaluated patients with MBC who received breast or chest wall RT with or without regional lymph node irradiation.Results2761 patients with breast cancer were treated with RT. Of them, 125 women with stage IV breast carcinoma were included. The median follow-up was 15 months (ranging from 3.8 to 168 months), when 54.7% of the patients had died; local progression was observed in 22.8% of the patients. The mean overall survival (OS) and local progression free survival (LoPFS) were 23.4 ± 2.4 months and 45.1 ± 2.9 months, respectively. Three- and five-year overall survival rates were, respectively, 21.2% and 13.3%. Local progression free survival was the same, 67.3%, at three and five years, respectively. Karnofsky Performance Status (KPS) (p = 0.015), number of metastatic sites (p = 0.031), RT dose (p = 0.0001) and hormone therapy (p = 0.0001) were confirmed as independent significant variables correlated with OS. The variables that were independently correlated with LoPFS were the number of previous chemotherapy lines (p = 0.038) and RT dose (p = 0.0001).ConclusionRT of the primary site in patients with MBC is well tolerated. The factors that presented positive impact on survival were good KPS, low disease burden (1–3 metastatic sites), and the use of hormone therapy.     

Efficacy and safety of eribulin as first- to third-line treatment in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes

ObjectivesDespite the survival benefit and acceptable tolerability of eribulin for advanced/metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes, there is limited evidence of the clinical benefit of early eribulin use. We investigated the efficacy and safety of first- to third-line eribulin use in patients with MBC.Materials and methodsIn this phase II, open-label, single-arm study conducted at 14 sites in Kyushu, Japan, women with histologically confirmed human epidermal growth factor receptor 2–negative MBC were enrolled between December 1, 2011 and November 30, 2013 (Data cut-off: November 30, 2014). Objective response rate (ORR; primary endpoint), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety were evaluated.ResultsOf 53 recruited patients, 47 were enrolled. The ORR was 17.0% (95% confidence interval, 7.6–30.8), DCR was 66.0% (51.2–77.8), median PFS was 4.9 months (3.5–7.0), DOR was 6.6 months (1.9–14.3), and median OS was 17.4 months (10.1–not evaluable). The common grade 3/4 adverse events were neutropenia (25 patients; 53.2%), leucopenia (16 patients; 42.1%) and febrile neutropenia (4 patients; 8.5%). Toxicity did not increase during the long-term treatment. Subgroup analysis indicated that first-line treatment led to higher ORR and prolonged PFS and OS than second-/third-line treatment and that incidence of adverse events in patients of second-/third-line treatment was not higher than that in patients of first-line treatment.ConclusionEribulin exhibited efficacy and manageable tolerability in Japanese women with pretreated MBC in first- to third-line use. (ID: UMIN000007121).     

Chemotherapy versus endocrine therapy as first-line treatment in patients with luminal-like HER2-negative metastatic breast cancer: A propensity score analysis

BackgroundAccording to current guidelines, endocrine therapy (ET) is recommended as first-line treatment of luminal-like metastatic breast cancer (MBC), whereas chemotherapy (CT) should be considered in presence of life-threatening disease. In daily practice, CT is often used outside of this clinical circumstance. Factors influencing first-line choice and the relative impact on outcome are unknown.MethodsA consecutive series of luminal-like HER2-negative MBC patients treated from 2004 to 2014 was analyzed to test the association of disease- and patient-related factors with the choice of first-line treatment (ET vs. CT). A propensity score method was used to estimate impact of first-line strategy on outcome.ResultsOf 604 consecutive luminal-like MBC patients identified, 158 cases were excluded due to unknown or positive HER2-status. Among 446 HER2-negative cases, 171 (38%) received first-line CT. On multivariate analysis, the only factors significantly associated with lower CT use were old age (OR 0.25, 95%C.I. 0.13–0.49) or presence of bone metastases only (OR 0.26, 95%C.I. 0.13–0.53). In propensity score matched population, no differences were observed between CT and ET as first-line treatment either in terms of overall survival (37.5 months and 33.4 months respectively, log-rank test, P = 0.62) or progression-free survival (13.3 months and 9.9 months respectively, log-rank test, P = 0.92).ConclusionsHigh percentage of patients with luminal-like MBC received CT as first-line therapy in real-life. The choice was mainly driven by age and site of metastases. With the limitations of a non-randomized comparison, no differences on patients' outcome were observed depending on the first-line strategy.     

Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period

IntroductionThe purpose of this study was to study the efficacy of subsequent treatment lines for metastatic breast cancer (MBC), as well as the association between radiologic objective response rate (ORR) and overall survival (OS).MethodsIn this retrospective study, consecutive patients treated for MBC in two centers in Greece from January 1, 1992, to December 31, 2016, were identified and clinicopathologic data regarding tumor characteristics and administered treatments were collected. The efficacy per treatment line in terms of ORR, progression-free survival (PFS) and OS, as well as the prognostic value of ORR at first line were investigated.ResultsA total of 977 patients with MBC were identified; 950 received any treatment. At first line, ORR was 43.5%, PFS 11.4 months (95% CI 10.4–12.4), and median OS 52.4 months (95% CI 47.7–57.1). Lower ORR and shorter PFS were observed with each subsequent line. Median OS was significantly longer for patients that had an objective response at first line, 61.9 months (95% CI 51.1–69.7) for responders versus 41.3 months (95% CI 44.1–63.3) for nonresponders (p < 0.001). In multivariable analysis, failure to achieve an objective response was an independent predictor of poor survival (hazard ratio 1.70, 95% CI 1.34–2.15, p < 0.001).ConclusionLate treatment lines for MBC seem to have limited efficacy, while response to first-line therapy is associated with long-term survival. The latter should be considered in the treatment strategy of patients with MBC.     

Trastuzumab,Pertuzumab, and Docetaxel as the First Line for HER-2-Positive Metastatic Breast Cancer among Arabs

IntroductionHuman epidermal growth factor receptor 2 (HER-2) targeted therapy regimens can improve tumor response in HER-2-positive metastatic breast cancer (MBC), with overall survival benefits.ObjectiveWe evaluated the efficacy of dual HER-2 blockade combined with chemotherapy for HER-2-positive MBC patients as a first-line therapy in our patient population.Patients and MethodsWe identified 75 patients at King Faisal Specialist Hospital and Research Center that received trastuzumab, pertuzumab, and docetaxel as a first-line therapy in HER-2 positive MBC in 2013–2016.ResultsMedian age at diagnosis was 45 years; 54.7% were estrogen receptor (ER)-positive. 10% of patients presented with only bone metastasis. The median follow-up time was 36 months with an objective response rate of 74.7% (complete response [CR] 18.7%; partial response [PR] 56%). The 5-year progression-free survival (PFS) and overall survival (OS) were 21% and 71.9% respectively, with a median PFS of 36 months (95% confidence interval [CI] 23.6–48.4). The 5-year OS for ER-negative and ER-positive patients was 93.9% and 59.4% respectively (p = 0.189); 23 patients experienced grade 1/2 toxicity and 2 patients had grade 3/4 toxicity. In terms of OS and PFS, the site of metastasis did not make any significant difference.ConclusionsFirst line pertuzumab, trastuzumab, and docetaxel for HER-2-positive MBC patients was found to be an effective and safe therapy in the Saudi population. This finding was consistent with the results seen in the CLEOPATRA trials.     

Predicting the survival benefit of local surgery in patients aged 70 years or older with stage IV breast cancer: A population-based analysis

PurposeThe aim of this study was to establish individualized nomograms to predict survival outcomes in older female patients with stage IV breast cancer who did or did not undergo local surgery, and to determine which patients could benefit from surgery.MethodsA total of 3,129 female patients with stage IV breast cancer aged ≥70 years between 2010 and 2015 were included in the Surveillance, Epidemiology, and End Results program. Multivariate Cox regression analysis was used to identify risk factors for overall survival (OS) and breast cancer-specific survival (BCSS). Survival analysis was performed using the Kaplan–Meier plot and log-rank test. Nomograms and risk stratification models were constructed.ResultsPatients who underwent surgery had better OS (HR = 0.751, 95% CI [0.668–0.843], P < 0.001) and BCSS (HR = 0.713, 95% CI [0.627–0.810], P < 0.001) than patients who did not undergo surgery. Patients with human epidermal growth factor receptor 2-positive, lung or liver metastases may not benefit from surgery. In the stratification model, low-risk patients benefited from surgery (OS, HR = 0.688, 95% CI [0.568–0.833], P < 0.001; BCSS, HR = 0.632, 95% CI [0.509–0.784], P < 0.001), while patients in the high-risk group had similar outcomes (OS, HR = 0.920, 95% CI [0.709–1.193], P = 0.509; BCSS, HR = 0.953, 95% CI [0.713–1.275], P = 0.737).ConclusionOlder female patients with stage IV breast cancer who underwent surgery had better OS and BCSS than those who did not in each specific subgroup. Patients in low- or intermediate-risk group benefit from surgery while those in the high-risk group do not.     

Real-World Efficacy of Fulvestrant Monotherapy as the First Treatment or Maintenance Treatment in Patients with Metastatic Breast Cancer

BackgroundFulvestrant 500 mg monotherapy is recommended as the first-line endocrine treatment in postmenopausal women with hormone receptor-positive metastatic breast cancer (MBC). It is also used in MBC maintenance treatment. However, few studies have compared the efficacy of fulvestrant during the initial treatment with that during maintenance treatment.Patients and MethodsMBC patients who were treated with fulvestrant either as initial therapy for metastatic disease or after progression following one line of chemotherapy between January 2016 and December 2017 were identified from the database of the Affiliated Hospital of Qingdao University. The primary end point was progression-free survival (PFS).ResultsThe study included 135 MBC patients who were treated with fulvestrant; 116 patients who received fulvestrant as first-line treatment were divided into 2 groups: the no-chemotherapy treatment (NCT) group received fulvestrant as initial therapy during disease progression, and the chemotherapy treatment (CT) group received fulvestrant as maintenance following disease stabilization or response to previous chemotherapy. The median PFS was 16 months in NCT patients and 8 months in the CT group. Patients who had a longer disease-free survival, no visceral metastasis and one metastasis site, benefited from fulvestrant as first-line treatment during disease progression. Patients with 2 or more metastasis sites benefited from chemotherapy as first-line treatment and fulvestrant as maintenance treatment.ConclusionsFulvestrant monotherapy showed good clinical activity and safety in patients with MBC who were treated upon disease progression and in those receiving maintenance therapy.     

Factors associated with improved outcome after surgery in metastatic breast cancer patients

Background

Recent studies suggest local surgical therapy improves survival in metastatic breast cancer (MBC). We evaluate the difference in outcome in patients with MBC after mastectomy versus breast conservation (BCT) and factors that influence outcome.

Methods

In a retrospective review of our prospective database, we identified patients who presented with MBC (1990 to 2007). Patient surgery type and clinicopathologic factors were reviewed. We compared OS between pts dependent on surgery and clinicopathologic factors.

Results

Of the 566 patients with MBC, 154 (27%) underwent removal of the primary tumor. Surgery was associated with an improved OS (33%) versus no surgery (20%) (P = 0.0015). Of those undergoing local therapy; mastectomy was associated with a 37% OS vs BCT with a 20% OS (P = 0.04).

Conclusions

Our study confirms that removal of the primary tumor in MBC is associated with improved overall survival. It appears that mastectomy is associated with a significantly improved overall survival.     

First-line bevacizumab-containing therapy for HER2-negative locally advanced/metastatic breast cancer: Real-world experience from >2000 patients treated in the multicentre AVANTI study

AimThe multicentre non-interventional AVANTI study assessed safety, effectiveness and patient-reported outcomes with approved first-line bevacizumab-containing regimens for HER2-negative locally recurrent/metastatic breast cancer (LR/MBC) in German routine oncology practice.MethodsEligible patients had HER2-negative LR/MBC, no bevacizumab contraindications and no prior chemotherapy for LR/MBC. Chemotherapy schedule, diagnostics and follow-up were at physicians’ discretion. Data were collected for 1 year after starting bevacizumab, then every 6 months for 1.5 years (maximum follow-up: 2.5 years). Patients and physicians rated treatment satisfaction. Subgroup analyses were prespecified in clinically relevant populations, including triple-negative breast cancer (TNBC).ResultsBetween November 1, 2009 and April 30, 2016, 2065 eligible patients at 346 centres received bevacizumab with paclitaxel or capecitabine. Patients receiving bevacizumab–capecitabine were less likely to have de novo disease and more likely to have TNBC, age ≥60 years and prior anthracycline/taxane and/or endocrine therapy. Median PFS was 12.6 (95% CI 11.9–13.2) months (12.8 with bevacizumab–paclitaxel, 10.5 with bevacizumab–capecitabine); median OS was 23.9 (95% CI 22.2–25.1) months. Outcomes were worse in patients with TNBC, prior anthracycline/taxane or prior endocrine therapy. Grade ≥3 adverse events occurred in 27% of patients. Treatment was discontinued for adverse events in 15%. Treatment satisfaction was rated as good or better by 304/394 responding patients (77%) at week 54 and in 1393/2065 patients (67%) by physicians overall.ConclusionsIn routine clinical practice, effectiveness and safety of first-line bevacizumab-containing therapy for LR/MBC were consistent with experience from phase III trials. Patient and physician treatment satisfaction showed high concordance.     

Does treatment sequence affect outcomes in patients with metaplastic breast cancer?

IntroductionWe compared characteristics and outcomes by treatment sequence among patients with metaplastic breast cancer (MBC), an aggressive subtype.MethodsWomen ≥18 years old with newly diagnosed Stage I-III MBC from 2003 to 2018 who received any treatment in our health system were identified. Unadjusted overall survival (OS) was estimated with the Kaplan-Meier method; the log-rank test was used to compare survival differences between recipients of neoadjuvant (NACT) and adjuvant chemotherapy (ACT).ResultsOf the 91 MBC patients identified, 60 received chemotherapy. NACT recipients (n = 20, median age 46.5 y) were younger than ACT recipients (n = 40, median age 60.5 y, p < 0.001) but similar with regards to race and radiation receipt. There was no significant OS difference between NACT and ACT recipients (log-rank p = 0.15), which remained true when patients were stratified by age (≥50 y vs < 50 y).ConclusionsAmong MBC patients, NACT recipients were younger than ACT recipients, but there was no survival difference by treatment sequence.     

Antibody-drug conjugates targeting TROP-2: Clinical development in metastatic breast cancer

Antibody drug conjugates (ADCs) combine the potent cytotoxicity of chemotherapy with the antigen -specific targeted approach of antibodies into one single molecule. Trophoblast cell surface antigen 2 (TROP-2) is a transmembrane glycoprotein involved in calcium signal transduction and is expressed in multiple tumor types. TROP-2 expression is higher in HER2-negative breast tumors (HR+/HR-) and is associated with worse survival. Sacituzumab govitecan (SG) is a first-in-class TROP-2-directed ADC with an anti-TROP-2 antibody conjugated to SN-38, a topoisomerase inhibitor via a hydrolysable linker. This hydrolysable linker permits intracellular and extracellular release of the membrane permeable payload enabling the “bystander effect” contributing to the efficacy of this agent. There was significant improvement in progression free survival (PFS) and overall survival (OS) with SG versus chemotherapy in pretreated metastatic triple negative breast cancer (TNBC), resulting in regulatory approval. Common adverse events (AE) reported were neutropenia and diarrhea. SG also demonstrated clinical activity versus chemotherapy in a phase III trial of HR+/HER2-metastatic breast cancer (MBC) and is under evaluation in first-line metastatic and early stage TNBC as well. Datopotamab deruxtecan (Dato-DXd) is a TROP-2 ADC that differs from SG in that it has a cleavable tetrapeptide linker and a more potent topoisomerase inhibitor payload. This construct is highly stable in circulation with a longer half-life than SG, and undergoes cleavage in presence of intracellular lysosomal proteases. Dato-DXd demonstrated preliminary efficacy in unselected metastatic TNBC, with common AEs of low-grade nausea and stomatitis. Dato-DXd is being investigated in phase III studies in metastatic TNBC and HR+/HER2- MBC. These novel TROP-2 ADCs have the potential to deliver enhanced efficacy with reduced toxicity in MBC and possibly in early stage breast cancer (EBC).