Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

PurposeAmong metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy.MethodsThe ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified.ResultsOf the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively.ConclusionThe duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated.     

Real-world data of HER2-low metastatic breast cancer: A population based cohort study

BackgroundWith the introduction of investigational human epidermal growth factor receptor 2 (HER2) targeting treatments, thorough understanding of breast cancer with different HER2 expression levels is critical. The aim of this study was to compare clinicopathologic characteristics and survival of patients with metastatic breast cancer according to the level of HER2 expression.MethodsWomen with distant metastatic breast cancer during 2008–2016 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO Database Network. Breast cancer samples were categorised as HER2 immunohistochemistry score 0 (IHC0), HER2-low or HER2+.ResultsAmong women with hormone receptor (HR) positive metastatic breast cancer (n = 989), 373 (38%) cancers were HER2 IHC0, 472 (48%) were HER2-low and 144 (15%) were HER2+. Among HR negative patients (n = 272), the proportion of HER2 IHC0, HER2-low and HER2+ was 110 (40%), 104 (38%) and 58 (21%) respectively.Within the HR + cohort, patients with HER2 IHC0 or HER2-low cancer were significantly older compared to HER2+ patients. This age difference was not seen in the HR-cohort. The localisation of distant metastases differed significantly between HER2 IHC0 or HER2-low versus HER2+ cases. Survival rates did not differ markedly by subtypes.ConclusionSubstantial proportion of patients had a HER2-low breast cancer. No clear differences in survival were found when comparing HER2 and HR status. Getting more granular insights in the level of HER2 expression and addressing HER2-low as a separate category could help to assess the impact of emerging treatment strategies. Therefore, more detailed information on HER2 expression should be routinely reported.     

Role of gemcitabine in metastatic breast cancer patients: a short review

Many active cytotoxic drugs, given according to a number of different regimens are approved for the treatment of metastatic breast cancer patients. However, these therapies have not changed the outcome of patients affected by this malignancy. As a consequence, the balance between chemotherapy-induced side effects and relief of cancer-related symptoms must be carefully considered in this setting. Gemcitabine is an antimetabolite that is incorporated as a triphosphate into DNA. As a single agent, it yields responses rates ranging from 14% to 37% in chemotherapy-na?ve patients and from 12% to 30% in patients previously treated with anthracyclines and/or taxanes. In combination with paclitaxel, it produces a significantly higher response rate (41.4% vs. 26.2%), longer time to progression (6.1 vs. 4 months) and significantly higher overall survival (18.6 vs. 15.8 months) than paclitaxel alone. In addition, a phase III study revealed that gemcitabine plus docetaxel is as effective as capecitabine plus docetaxel, but causes significantly less non-haematologic toxicity. Lastly, in another phase III trial, progression free survival was significantly longer with the combination of gemcitabine plus vinorelbine than with vinorelbine alone (6 vs. 4 months), but without a significant difference in overall survival; the incidence of haematologic toxicity was higher in the group treated with combined therapy. Novel gemcitabine combinations are being investigated in phase II studies.     

Impact of body mass index on the efficacy of endocrine therapy in patients with metastatic breast cancer - A retrospective two-center cohort study

BakgroundThe aim of this study was to investigate the impact of body mass index (BMI) on the efficacy of endocrine therapy in postmenopausal women with metastatic hormone receptor breast cancer (HR+BC) as well as to identify if the potential difference in efficacy was associated with Fulvestrant only or both aromatase inhibitors (AIs) and Fulvestrant.MethodsA consecutive cohort of postmenopausal women with HR+metastatic breast cancer that have received endocrine therapy including Fulvestrant as a metastatic treatment strategy at the Departments of Oncology in Eskilstuna and Uppsala, Sweden, between 2008 and 2016 were identified. The primary outcome of the study was time to disease progression (TTP) during the treatment with Fulvestrant in overweight and obese women compared to patient with normal BMI.ResultsIn total, 173 patients were enrolled in the study cohort, amongst these, 141 patients received both Fulvestrant and AIs and 32 received only Fulvestrant. No statistical significant association was observed between the three BMI categories and TTP, during Fulvestrant treatment (p = 0.136). The rates of objective response and clinical benefit due to Fulvestrant were similar among patients with normal weight, overweight and obesity, respectively.ConclusionsNo difference in treatment efficacy was seen between normal, overweight and obese women with metastatic HR+BC, when treated with Fulvestrant. Until further research with prospective studies is available, there is no evidence to support any modification in how Fulvestrant treatment is used in patients with metastatic breast cancer in regard to BMI.     

Oral etoposide in heavily pre-treated metastatic breast cancer: A retrospective series

BackgroundPatients with metastatic breast cancer (MBC) can derive clinical benefit from several subsequent lines of chemotherapy. However, in heavily pre-treated patients, agents with clinical activity, a favourable side effects profile and a convenient administration modality are preferred.Patients and MethodsWe retrospectively analyzed 110 patients with previously treated MBC, who received oral etoposide at the dose of 50 mg/day for 20 days in 28 days cycles, between 2003 and 2017. Because this was not a prospectively planned study, to describe the clinical performance of oral etoposide we adopted the approach suggested by Dzimitrowicz and colleagues (J Clin Oncol. 2016; 34:3511–17); Tumour Response (TR) was defined as the proportion of physician-reported clinical or imaging response; Prolonged Duration on Therapy (PDT) as the proportion of non-progressing patients whose treatment lasted more than 6 months. Furthermore, we evaluated median duration on therapy (TD) and median Overall Survival (OS) by the Kaplan Meier method.ResultsThe median number of previous chemotherapy lines was 5 (range 2–8). TR, PDT, median TD and median OS were 6.4%, 18.2% 4 (range 3.5–4.5) and 10.6 (range 8.4–12.8) months respectively. Interestingly, etoposide activity was unrelated to the number of previous lines and type of metastatic involvement. Oral etoposide was well tolerated with only two patients discontinuing therapy due to toxicity.ConclusionsIn this large, single Institution, real practice analysis oral etoposide is a valuable and safe option for pre-treated metastatic breast cancer patients and might be considered in patients failing other approaches, but still suitable for chemotherapy.     

Safety analysis,association with response and previous treatments of everolimus and exemestane in 181 metastatic breast cancer patients: A multicenter Italian experience

PurposeThe everolimus and exemestane combination represents a treatment option for the endocrine sensitive metastatic breast cancer (MBC) patients. The toxicity profile reported in the Bolero 2 trial showed the feasibility in the selected patients. Few data are available for the unselected population.MethodsIn order to evaluate the safety in the unselected population of the clinical practice and to evaluate a possible association of toxicities with previous treatments, clinical data from 181 consecutive patients were retrospectively collected.ResultsDue to toxic events, everolimus dosage was reduced to 5 mg in 27% of patients. No association was found in the analysis between toxicity and number of prior therapies, neither between toxicity and response. In the multivariate analysis the previous exposure to anthracyclines for advanced disease represents the only predictive factor of developing grade ≥2 toxicity (OR = 2.85 CI 95% 1.07–7.59, p = 0.036).ConclusionsThe association of everolimus and exemestane has confirmed to be a safe and effective treatment for endocrine sensitive MBC patients even in routine clinical practice. The rate of treatment discontinuation due to toxicity is low and none association between previous number of treatments and response or between toxicity and response was found.     

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.     

Long-term follow-up of patients with metastatic breast cancer treated by trastuzumab: Impact of institutions

PurposeTrastuzumab in Human Epidermal growth Receptor 2-positive (HER2+) metastatic breast cancer (MBC) was established as standard therapy since 2001. The objective of this study was to search for significant prognostic factors in patients with HER2+ MBC treated by trastuzumab taking into account the institution where the treatment was given.Patients & methodsAll patients with HER2+ MBC treated by trastuzumab between 2001 and 2010 in the 8 hospitals of Franche Comte region were analysed. Univariate and multivariate analysis were conducted to search for factors related to overall survival (OS).ResultsAmong 1234 patients with MBC treated by chemotherapy between 2001 and 2010, 217 patients received trastuzumab. In this subset, the median age was 60 years, 8% and 38% had brain and liver metastases at first occurrence of MBC, 36% of, tumours were hormonal receptors positive. Patients were treated in 48% and 52% of cases in specialized and in general hospitals, respectively. The median OS length was 45.2 months (IQR 23.2–89.3 months). In univariate analysis the following factors were significantly related to favourable OS: inclusion in clinical trials, treatment in a specialized hospital, positive hormonal receptors status, age <50. In multivariate analysis remained significant: treatment in specialized hospital (aHR 0.78; 95%CI 0.64–0.94; p = 0.03) and age <50 (aHR 0.76; 95%CI 0.59–0.95; p = 0.02).ConclusionExposure to trastuzumab erases all established prognostic factors at the metastatic setting. The fact that patients treated in specialized hospitals presented a longer survival emphasizes the dramatic impact of this therapy and the relevance to optimize its use.     

Favorable survival with combined treatment in a metastatic breast cancer patient undergoing hemodialysis: A case report

IntroductionManagement of breast cancer patients undergoing hemodialysis (HD) is difficult because of a lack of evidence about drug selection, dose adjustment, and surgical procedures. We herein present a case of metastatic breast cancer in a patient undergoing HD.Presentation of caseA 58-year-old Japanese woman with breast cancer undergoing HD underwent total mastectomy of the left breast and left axillary dissection. Histopathological examination revealed invasive ductal carcinoma, and the diagnosis was pT2N3cM0 Stage ⅢC. Immunostaining of the resected specimen indicated that the tumor was estrogen receptor-positive, progesterone receptor-negative, human epithelial growth factor receptor 2-positive, and the Ki-67 labeling index was 70%. A postoperative positron emission tomography/computed tomography (PET/CT) scan indicated fluorodeoxyglucose uptake in the supraclavicular nodes. She received adjuvant therapy of epirubicin and cyclophosphamide followed by docetaxel, trastuzumab (T-mab) and radiation therapy. However, she developed multiple liver metastases during adjuvant T-mab and hormone therapy. Therefore, her regimen was changed to trastuzumab emtansine (T-DM1) as first-line therapy, T-mab, pertuzumab (P-mab), and eribulin as second-line therapy, and T-mab, P-mab, and weekly paclitaxel as third-line therapy. Eventually, she was administered fourth-line treatment of T-mab, P-mab, and vinorelbine because of adverse events. She has survived more than 25 months after the initial detection of recurrence of breast cancer and maintained quality of life.ConclusionWe report a case of breast cancer in a patient undergoing HD. It is very difficult to identify the appropriate drugs and dosages in patients undergoing HD to improve survival and quality of life.     

Impact of age at diagnosis of metastatic breast cancer on overall survival in the real-life ESME metastatic breast cancer cohort

BackgroundYoung age is a poor prognostic factor in early stage breast cancer (BC) but its value is less established in metastatic BC (MBC). We evaluated the impact of age at MBC diagnosis on overall survival (OS) across three age groups (<40, 40 to 60 and > 60 years(y)).MethodsESME MBC database is a national cohort, collecting retrospective data from 18 participating French cancer centers between January 01, 2008 and December 31, 2014.ResultsAmong 14 403 women included, 1077 (7.5%), 6436 (44.7%) and 6890 (47.8%) pts were <40, 40–60 and > 60 y respectively. Pts <40 had significantly more aggressive presentations than other age groups: more frequent HER2+ (25.7 vs 15.3% in >60y) and triple negative subtypes (27.4 vs 14.6% in >60y), and more frequent visceral involvement (36.3 vs 29.8% in >60y). At a median follow-up of 48 months, median OS differed across age groups: 38.8, 38.4 and 35.6 months for pts <40, 40–60 and > 60y, respectively (p < 0.0001). Compared to pts <40y, older pts had a statistically significant higher risk of death (all causes of death included), although of limited clinical value (HR = 1.1, IC 95%:1.01–1.20). There was a significant trend for better OS in pts <40y with HER2+ and luminal diseases. A possible explanation is a greater use of anti-Her2 therapies as first-line treatments: 86.6, 81.9 and 74.9% for pts <40, 40–60 and > 60y, respectively (p < 0.0001).ConclusionAlthough young age seems associated with more aggressive presentations at diagnosis of MBC, it has no deleterious effect on OS in this large series.     

Family history of breast cancer,mammographic breast density and breast cancer risk: Findings from a cohort study of Korean women

BackgroundThis study investigated whether the association between family history of breast cancer in first-degree relatives and breast cancer risk varies by breast density.MethodsWomen aged 40 years and older who underwent screening between 2009 and 2010 were followed up until 2020. Family history was assessed using a self-reported questionnaire. Using Breast Imaging Reporting and Data System (BI-RADS), breast density was categorized into dense breast (heterogeneously or extremely dense) and non-dense breast (almost entirely fatty or scattered areas of fibro-glandular). Cox regression model was used to assess the association between family history and breast cancer risk.ResultsOf the 4,835,507 women, 79,153 (1.6%) reported having a family history of breast cancer and 77,238 women developed breast cancer. Family history led to an increase in the 5-year cumulative incidence in women with dense- and non-dense breasts. Results from the regression model with and without adjustment for breast density yielded similar HRs in all age groups, suggesting that breast density did not modify the association between family history and breast cancer. After adjusting for breast density and other factors, family history of breast cancer was associated with an increased risk of breast cancer in all three age groups (age 40–49 years: aHR 1.96, 95% confidence interval [CI] 1.85–2.08; age 50–64 years: aHR 1.70, 95% CI 1.58–1.82, and age ≥65 years: aHR 1.95, 95% CI 1.78–2.14).ConclusionFamily history of breast cancer and breast density are independently associated with breast cancer. Both factors should be carefully considered in future risk prediction models of breast cancer.     

De novo metastatic lobular breast carcinoma: A population-based study from SEER database

PurposePatients with metastatic lobular breast carcinoma constitute a heterogeneous group with distinguishing features. Our aim was to describe the features and survival of them, and further subdivide them into subcategories for prognostic stratification and treatment planning.Patients and methodsPatients with de novo metastatic breast cancer from 2010 to 2018 were identified using the SEER database. Multivariate logistic regression analysis was conducted to calculate odds ratios. The within-pair difference was minimized by propensity score matching. Multiple comparisons based on Cox proportional hazards model were performed to investigate the interactions of M1 subcategory and treatment modality on survival.ResultsA total of 1,675 patients with de novo metastatic lobular breast carcinoma were identified, they were more likely to have HR+/HER2- subtype, low histologic grade, low T/N stage, fewer metastatic sites, but worse prognosis compared with patients with metastatic ductular breast carcinoma. The M1 stage was subdivided into 3 subcategories with significantly different prognoses. The benefits of primary tumor surgery were more pronounced in M1a/b disease, whereas the benefits of chemotherapy increased with the progression of metastatic disease.ConclusionPatients with metastatic lobular breast carcinoma have unique clinicopathological characteristics and metastatic patterns. M1 subcategory assists prognosis stratification and treatment planning for such patients.     

T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer

BackgroundWe reported the results of an Italian large retrospective analysis that evaluated the effectiveness and safety of T-DM1 in ‘field-practice’ breast cancer patients. We performed a sub-analysis to investigate the clinical activity of T-DM1 in patients with brain metastases (BMs).MethodsThe records of 87 adult women with HER2-positive breast cancer and BMs treated with T-DM1 were reviewed. Their clinical outcomes were compared with those of 216 patients without central nervous system (CNS) involvement.ResultsResponse to T-DM1 treatment in BMs was available for 53 patients in the BM group (60.9%): two patients reported a complete response (3.8%), 11 patients obtained partial response (20.7%; overall response rate: 24.5%), 16 patients had a stable disease (30.1%). Regarding extracranial disease, a total of 77 and 191 patients were evaluable for response in BM group and non-BM group, respectively. The overall response rate was 35.1% in the BM group and 38.3% in the non-BM group; disease control rate was 53.3% and 66.6%, respectively.At a median follow-up of 16 months (range: 1–55), median cumulative progression-free survival (PFS) was 7 months (95% CI: 5.4–8.6) in the BM group and 8 months (95% CI: 5.7–10.3) in the non-BM group. In the second-line setting, PFS was 5 (95% CI: 3.1–6.9) versus 11 (95% CI: 7.1–14.9) months (p = 0.01). Overall survival was 14 months (95% CI: 12.2–15.8) in the BM group and 32 months (95% CI: 24.4–39.6) in the non-BM group (p < 0.0001).ConclusionsT-DM1 is active in breast cancer patients with BMs.     

The first two lines of chemotherapy for anthracycline-naive metastatic breast cancer: A comparative study of the efficacy of anthracyclines and non-anthracyclines

For anthracycline-naive metastatic breast cancer (AN-MBC), early anthracycline treatment is a common practice. However, with the availability of newer chemotherapies, comparative studies on the efficacy of anthracyclines and non-anthracyclines as early treatments for AN-MBC are lacking. We collected retrospective clinicopathological data from 253 AN-MBC patients treated at National Taiwan University Hospital between 2001 and 2006. Patients were categorised into anthracycline or non-anthracycline groups according to their regimens in the first two lines of chemotherapy. The overall survival (OS, 33.3 vs. 34.2 months, p = 0.179), time to treatment failure of the first two lines of chemotherapy drugs (13.3 vs. 12.7 months, p = 0.104) and best composite response rate (59.5% vs. 61.1%, p = 0.81) were not significantly different between the two groups. Multivariate analysis showed that early anthracycline treatment was not a significant prognostic factor of OS (p = 0.052). Thus, the results of this study show that anthracyclines may not be necessary as an early treatment option for AN-MBC.     

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.     

Spiritual expression and immune status in women with metastatic breast cancer: an exploratory study

This exploratory study examined relationships between spirituality and immune function in 112 women with metastatic breast cancer. Spirituality was assessed by patient reports of frequency of attendance at religious services and importance of religious or spiritual expression. White blood cell counts, absolute numbers of lymphocytes, T-lymphocyte subsets, and natural killer cells were assessed by flow cytometry. Assessments of natural killer cell activity and delayed-type hypersensitivity responses to skin test antigens provided two measures of functional immunity. In analyses controlling for demographic, disease status, and treatment variables, women who rated spiritual expression as more important had greater numbers of circulating white blood cells and total lymphocyte counts. Upon examination of relationships with lymphocyte subsets, both helper and cytotoxic T-cell counts were greater among women reporting greater spirituality.     

Phase II trial of paclitaxel and uracil--tegafur in metastatic breast cancer. TEGATAX trial

This Phase II trial investigated the combination paclitaxel (P) and uracil-tegafur (UFT) in patients with metastatic breast cancer (MBC).

Methods

Main eligibility criteria included HER-2 negative MBC, ECOG performance status of 0-2, exposure to 1-2 prior chemotherapy regimen in the metastatic setting, previous exposure to an anthracycline containing regimen either at metastatic or adjuvant setting. Each 35-day cycle consisted of P at 80 mg/m² by intravenous infusion on days 1, 8, 15, 22 and 29 and oral UFT at 300 mg/m² TID (three time a day) from days 1-28 and oral folinic acid at 90 mg QD (one a day).

Results

Between March 2003 and December 2007, 31 patients were enrolled. Median age was 66 years (range 44-78). All tumours were HER-2 negative and 7% were triple negative (ER, PgR, HER-2). The majority of patients had visceral disease (81%). All patients had received an anthracycline containing regimen and 74% had a previous docetaxel containing treatment. Median of 4 and 3 cycles of P and UFT were administered with a relative dose intensity of 85.3% and 94.3%, respectively. Twelve (40%)(95% CI: 22.5-57.5) confirmed ORR were observed. Stable and progression disease were reported in 43% and 17% of cases. Median Response duration was 8.4 month (95% CI: 4.9-11.7), median Time to progression was 9.5 months (95% CI: 6.6-13.8) and median Overall Survival was 23.5 months (95% CI: 16.8-37.2). Thirteen pts (43%) experienced a grade 3 or 4 adverse events (AEs): One death occurred related to the study drugs (febrile neutropenia). Chemotherapy was discontinued due to toxicity in 30% of pts

Conclusions

Accrual was closed in January 2008 due to concerns regarding the degree and accumulative nature of AEs. Nonetheless, the ORR is encouraging and warranted further studies with adapted doses and schedules.