Regimen For Advanced Breast Cancer Research Articles

Abstract OT2-27-02: A prospective phase II study on efficacy and safety of anlotinib combined with fulvestrant in patients with HR-positive and HER2-negative, secondary endocrine-resistant, locally advanced or metastatic breast cancer

Abstract Background: The management of HR-positive, HER2-negative metastatic breast cancer includes endocrine monotherapy or combination regimens, both with benefit diminishing as resistance develops. Nowadays, various studies have demonstrated that estrogen interacts with many angiogenic pathways and is an important mechanism for resistance leading to the question of whether combination with antiangiogenesis and antiestrogen therapies could be an appropriate therapeutic modality. Anlotinib is a novel multi-target tyrosine kinase inhibitor that effectively inhibit VEGFR, FGFR, PDGFR, c-KIT, c-MET and RET. Previous studies have proven the efficacy of both anlotinib monotherapy and combination regimens in advanced breast cancer. This phase II study aims to preliminarily evaluate the efficacy and safety of anlotinib combined with endocrine therapy. Methods: This study is a prospective, single-arm, open-label, phase II clinical trial. Eligible patients were women aged 18 years or older of any menopausal status (the premenopausals had to receive luteinising-hormone-releasing-hormone agonist at least 4 weeks before randomisation) and with ECOG status 0-1, who had HR-positive (estrogen receptor- and/or progesterone receptor-positive) and HER2-negative, secondary endocrine-resistant (defined as disease relapse within 12 months after at least 24 months endocrine adjuvant therapy, or disease progress after at least 6 months endocrine salvage therapy), locally advanced or metastatic breast cancer. Mainly exclusive criteria included the previous use of angiogenic inhibitors or fulvestrant, prior more than one line of chemotherapy, visceral crisis, and uncontrolled CNS metastases. Eligible patients were treated with oral anlotinib (12 mg once daily on days 1-14, repeated every 21 days) plus intramuscular fulvestrant (500 mg on days 1 and 15 of cycle one, and then on day one of each subsequent 28 days cycle) till disease progression or intolerant toxicity. The primary endpoints is progression-free survival (PFS) and the secondary endpoints include overall response rate (ORR), Clinical Benefit Rate (CBR), overall survival (OS), and safety. In the part of statistical analysis, 40 patients are required to have a 80% power to detect significant improvement in median progression-free survival from 5.8 (fulvestrant alone) to 10 (fulvestrant combined with anlotinib) months, if tested at a two-sided significance level of α=0.05. This study is currently enrolling patients and planned completion in July, 2023. Registration information: ChiCTR2100047080. Results: The trial is in progress. Conclusion: The trial is in progress. Citation Format: Xiaojia Wang, Jian Huang. A prospective phase II study on efficacy and safety of anlotinib combined with fulvestrant in patients with HR-positive and HER2-negative, secondary endocrine-resistant, locally advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-27-02.

Real-World Outcome of Platinum-Based Chemotherapy in Advanced Breast Cancer (ABC): A Retrospective Study from a Tertiary Cancer Center in India

Abstract Introduction There is a paucity of data on platinum-based chemotherapy in advanced breast cancer (ABC) from developing countries like India. Objectives The objectives were to analyze the efficacy and safety of platinum-based chemotherapy in patients with ABC. Materials and Methods This was a retrospective study of 35 patients with ABC who were treated with platinum-based chemotherapy (gemcitabine and carboplatin, [GC]) in a tertiary cancer center in India from August 2015 to November 2019. The inclusion criteria were patients with ABC, who had received palliative chemotherapy with GC. The exclusion criteria were patients who had received less than two cycles of GC and patients who received platinum-based chemotherapy for neuroendocrine carcinoma of the breast. Results The median age was 45 years (range: 28–68 years). All patients were female (97%) except one male (3%). The histology was ductal carcinoma (77%), mixed (17%), and others (6%). Out of the 12 patients tested for breast cancer (BRCA) gene mutation, six patients had a BRCA mutation. Patients with metastatic and locally progressive disease were 91 and 9%, respectively. The median number of prior lines of systemic therapy for metastatic disease was 1 (range: 0–5). The median number of sites of metastasis was 2 (range: 0–5). Patients with visceral crises were 23%. The median number of cycles of GC chemotherapy received was 6 (range: 2–6). A dose reduction in chemotherapy was done in 74%. The responses among 34 evaluable patients were complete response (11%), partial response (24%), stable disease (41%), and progressive disease (24%). Grade 3 or more hematological and nonhematological toxicities were observed in 69 and 9%, respectively. The median progression-free survival and overall survival were 6 and 8 months, respectively. The 1-year progression-free survival and overall survival were 19 and 34%, respectively. Multivariate analysis showed that patients who had received more than 3 cycles had a better outcome. Conclusion GC was an active and well-tolerated regimen in ABC regardless of the receptor status. Further prospective randomized studies are warranted to assess the optimal regimen in patients with triple-negative breast cancer.

151P - Peripheral cytotoxic T cell correlates with tumor mutational burden and is predictive for progression free survival in advanced breast cancer

BackgroundThe clinical relevance of the host immune system in breast cancer has long been studied. Peripheral blood lymphocytes show a great potential due to the advantages of minimal invasiveness, ease of access and high homogeneity. Peripheral blood lymphocytes consists of varying subpopulations. Each subpopulation of peripheral lymphocytes plays a different part in anti-tumor immunity and thus may have different clinical relevance. However, the related studies have rarely been reported. MethodsA total of 264 advanced breast cancer patients (ABCs) were consecutively recruited at our center between January 2015 and September 2018. All patients received the conventional regimen for advanced breast cancer. Detection of peripheral blood lymphocytes at baseline was accomplished in all 264 patients with 118 patients having ctDNA detection simultaneously. The median survival was estimated by Kaplan-Meier curve, with difference detection by log-rank test and Cox proportional hazards regression model. ResultsThe median follow-up time of the study was 13.0 months. Multivariate analysis confirmed that cytotoxic T cell (CTL) was an independent prognostic factor of PFS (P=0.024). Pierson correlation analysis showed one and only positive correlation between tumor mutational burden (TMB) and CTL level at baseline (P=0.015). Furthermore, baseline CTL level was only confirmed in the HER2-positive subgroup (P<0.001) but not in the HR-positive (P=0.333) or in the TNBC subgroup (P=0.322). For the entire cohort, the TMB high (>75%) group had a signifiantly shorter PFS (P=0.004) than TMB low. In the HER2-positive subgroup, the PFS of the TMB high group was shorter than for the TMB low group (P<0.001). We further use survival data obtained from the TCGA database as a validation set to confirm our findings. As expected, 24 out of 105 HER2-positive patients with TMB high were found to have shorter PFS than TMB low (HR=0.2, 95% CI: 0.06∼0.71, P=0.005). ConclusionsPheripheral CTL to total lymphocyte proportion is predictive for PFS in HER2-positive ABCs but not in TNBC or HR positive. Since CTL proportion was found to positively correlate with TMB and high TMB indicates shorter PFS. Thus, the negative prognositc role of CTL was, at least, partly due to the TMB of ABCs. Legal entity responsible for the studyPeking University Cancer Hospital-Beijing Cancer Hospital. FundingNational Natural Science Foundation of China. DisclosureAll authors have declared no conflicts of interest.

Abstract CT010: Efficacy results based on PIK3CA status in BELLE-3: A Phase 3 study of buparlisib (BKM120) + fulvestrant in postmenopausal women with aromatase inhibitor-treated, HR+/HER2- ABC after progression on an mTOR inhibitor

Abstract Introduction The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway is often activated in endocrine therapy (ET)-resistant, hormone receptor-positive (HR+) breast cancer (BC). Adding a PI3K inhibitor (PI3Ki) to ET may overcome ET or mTOR inhibitor (mTORi) resistance. In the Phase 3 BELLE-2 study, the pan-PI3Ki buparlisib (BUP) + fulvestrant (FULV) prolonged progression-free survival (PFS) in patients (pts) with HR+, human epidermal growth factor receptor 2-negative (HER2–) advanced BC (ABC), particularly in pts with PIK3CA mutations in circulating tumor DNA (ctDNA). Here, we report biomarker results from BELLE-3 (NCT01633060). Methods In total, 432 postmenopausal women with HR+/HER2– ABC who previously received an aromatase inhibitor and progressed on/within 30 days of ET + mTORi treatment were enrolled. Pts must not have received &amp;gt;1 chemotherapy regimen for ABC, or any prior PI3Ki, protein kinase B (AKT) inhibitor, or FULV. Pts were randomized 2:1 to receive BUP (100 mg/day) + FULV (500 mg) or placebo (PBO) + FULV, stratified by visceral disease status. PIK3CA status was assessed by BEAMing (exons 9 and 20 only) in plasma ctDNA collected at baseline, and in archival tumor samples by polymerase chain reaction (PCR) and next-generation sequencing (NGS). The primary endpoint was locally assessed PFS (RECIST v1.1). Secondary endpoints included overall survival, overall response rate, PFS by ctDNA PIK3CA status, quality of life, and safety; with exploratory PFS analyses by PIK3CA status in tumor tissue. Results BELLE-3 met its primary objective: PFS was significantly prolonged for BUP vs PBO, with hazard ratio (HR) 0.67 (95% confidence interval [CI]: 0.53–0.84; p&amp;lt;0.001) and median PFS 3.9 vs 1.8 months. PIK3CA mutations were present in 135/348 (39%) available ctDNA samples, 109/321 (34%) tumor samples (by PCR), and 76/185 (41%) tumor samples (by NGS). PFS benefit for BUP vs PBO was higher in the PIK3CA-mutant ctDNA group (HR 0.46 [95% CI: 0.29–0.73]; median PFS 4.2 vs 1.6 months) than the PIK3CA-wild-type (WT) group (HR 0.73 [95% CI: 0.53–1.00]; median PFS 3.9 vs 2.7 months). PFS benefit was also higher in the PIK3CA-mutant tumor tissue group by PCR (HR 0.39 [95% CI: 0.23–0.65]) than the PIK3CA-WT group (HR 0.83 [95% CI: 0.60–1.14]), and in the PIK3CA-mutant tumor tissue group by NGS (HR 0.46 [95% CI: 0.26–0.82]) than the PIK3CA-WT group (HR 0.62 [95% CI: 0.40–0.97]). PIK3CA status in ctDNA and archival tissue by PCR had an overall concordance of 83%, with a sensitivity of 79% and specificity of 85%. Conclusions BELLE-3 met its primary endpoint in the full population. PFS benefit for BUP vs PBO was higher in pts with PIK3CA mutations detected in ctDNA or archival tissue (by PCR or NGS). Ongoing Phase 3 studies with PI3Kα-selective inhibitors will confirm the predictive value of PIK3CA mutations in ctDNA and tumor tissue on efficacy. Citation Format: Ruth O'Regan, Carlos L. Arteaga, Thomas Bachelot, Eva Ciruelos, Per E. Lønning, Banu Sankaran, Ying A. Wang, Nicolas Scheuer, Dalila Sellami, Samit Hirawat, Angelo Di Leo. Efficacy results based on PIK3CA status in BELLE-3: A Phase 3 study of buparlisib (BKM120) + fulvestrant in postmenopausal women with aromatase inhibitor-treated, HR+/HER2- ABC after progression on an mTOR inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT010. doi:10.1158/1538-7445.AM2017-CT010

Trastuzumab emtansine versus treatment of physician's choice in patients with previously treated HER2-positive metastatic breast cancer (TH3RESA): final overall survival results from a randomised open-label phase 3 trial

In the randomised, parallel assignment, open-label, phase 3 TH3RESA study, progression-free survival was significantly longer with trastuzumab emtansine versus treatment of physician's choice in previously treated patients with HER2-positive advanced breast cancer. We report results from the final overall survival analysis of the TH3RESA trial. Eligible patients for the TH3RESA trial were men and women (aged ≥18 years) with centrally confirmed HER2-positive advanced breast cancer previously treated with both trastuzumab and lapatinib (advanced setting) and a taxane (any setting) and with progression on two or more HER2-directed regimens in the advanced setting. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2, left ventricular ejection fraction of at least 50%, and adequate organ function. Patients were randomly assigned (2:1) by an interactive voice and web response system with permuted block randomisation in blocks of six to receive trastuzumab emtansine (3·6 mg/kg intravenously every 21 days) or treatment of physician's choice administered per local practice. Randomisation was stratified by world region, number of previous regimens for advanced breast cancer, and presence of visceral disease. On Sept 12, 2012, the study protocol was amended to allow patients with disease progression to crossover from treatment of physician's choice to trastuzumab emtansine. The coprimary endpoints for TH3RESA were investigator-assessed progression-free survival and overall survival in the intention-to-treat population. We report results from a preplanned second interim analysis of overall survival, which was planned for when approximately 67% (n=330) of 492 expected deaths had occurred. This study is registered with ClinicalTrials.gov, number NCT01419197. Between Sept 14, 2011, and Nov 19, 2012, 602 patients were enrolled from 146 centres in 22 countries and randomly assigned to trastuzumab emtansine (n=404) or treatment of physician's choice (n=198). At data cutoff (Feb 13, 2015), 93 (47%) of 198 patients in the physician's choice group had crossed over to trastuzumab emtansine. Overall survival was significantly longer with trastuzumab emtansine versus treatment of physician's choice (median 22·7 months [95% CI 19·4-27·5] vs 15·8 months [13·5-18·7]; hazard ratio 0·68 [95% CI 0·54-0·85]; p=0·0007). As the stopping boundary for overall survival was crossed, this overall survival analysis serves as the final and confirmatory analysis of overall survival and the study was terminated according to the protocol. The incidence of grade 3 or worse adverse events was 161 (40%) of 403 patients in the trastuzumab emtansine group and 87 (47%) of 184 patients in the treatment of physician's choice group. Of the most common grade 3 or worse adverse events (affecting ≥2% of patients in either group), those with a 3% or greater difference in incidence between groups that were more frequent with treatment of physician's choice than with trastuzumab emtansine were diarrhoea (three [1%] of 403 patients in the trastuzumab emtansine group vs eight [4%] of 184 patients in the treatment of physician's choice group), neutropenia (ten [3%] vs 29 [16%]), and febrile neutropenia (one [<1%] vs seven [4%]); whereas those that were more frequent with trastuzumab emtansine were thrombocytopenia (24 [6%] of 403 patients vs five [3%] of 184 patients) and haemorrhage of any type (17 [4%] of 403 vs one [<1%] of 184). Serious adverse events were reported in 102 (25%) of 403 patients in the trastuzumab emtansine group and 41 (22%) of 184 in the physician's choice group. Deaths from adverse events were reported in three patients (2%) in the physician's choice group (of which one was judged to be treatment related) and nine (2%) in the trastuzumab emtansine group (of which three were judged to be treatment related). In patients who had progressed on two or more HER2-directed regimens, trastuzumab emtansine treatment resulted in a significant improvement in overall survival versus treatment of physician's choice. These data further solidify the role of trastuzumab emtansine in the management of patients with previously treated HER2-positive advanced breast cancer, and validate HER2 as a therapeutic target even after multiple lines of previous therapy. F Hoffman-La Roche/Genentech.

Abstract OT1-03-15: The METRIC trial: A randomized international study of the antibody-drug conjugate glembatumumab vedotin (GV or CDX-011) in patients with metastatic gpNMB-overexpressing triple-negative breast cancer (TNBC)

Abstract Background Glycoprotein NMB (gpNMB) is an internalizable transmembrane protein overexpressed in approximately 20% of breast cancer (BC), including approximately 40% of TNBC. gpNMB is a poor prognostic marker in BC (Rose CCR 2010) and preclinically has been implicated in tumor invasion, metastasis, and angiogenesis. GV is a novel antibody-drug conjugate targeting the potent cytotoxin monomethylauristatin E (MMAE) to gpNMB overexpressing cancer cells. In a Phase I/II study and the Phase II "EMERGE" study, GV demonstrated promising activity with TNBC patients (pts) deriving the greatest benefit and exhibiting the highest degree of gpNMB overexpression. GV was well-tolerated with the most frequent treatment-related toxicities consisting of rash, neutropenia, and neuropathy. In subset analyses of the EMERGE trial, objective response rate (ORR) was 30% (7/23) for GV vs. 9% (1/11) for investigator's choice in tumors with gpNMB overexpression (&amp;gt;25% of tumor epithelium); 18% (5/28) vs. 0% (0/11) in TNBC; and 40% (4/10) vs. 0% (0/6) in gpNMB-overexpressing TNBC for GV and IC respectively, with apparent improvements in progression-free survival (PFS; hazard ratio (HR) = 0.11) and overall survival (OS; HR = 0.14). Trial design The METRIC Trial (NCT#01997333) is an international (USA, CA, Aus), two-arm phase II study. Pts are randomized 2:1 to GV (1.88 mg/kg IV q 21 days) or capecitabine, a current standard of care for this population (2,500 mg/m2 daily for d1-14, q21 days) until progression or intolerance. Crossover is not permitted. Eligibility criteria Key eligibility criteria include: &amp;gt;25% of tumor epithelium gpNMB+ by central immunohistochemistry (IHC) screening of archival tissue; estrogen receptor and progesterone receptor &amp;lt;10% and HER2 negative [0-1+ IHC, or ISH copy number &amp;lt;4.0/ratio &amp;lt;2.0] by local assessment; ECOG 0-1; taxane resistance; anthracycline exposure (if indicated); &amp;lt;2 chemotherapy regimens for advanced BC; measurable disease; no persistent Grade &amp;gt;2 toxicity. Specific aims The primary endpoint is PFS per independent, blinded central review committee according to RECIST 1.1. Secondary endpoints are ORR, duration of response, OS, safety, pharmacokinetics and pharmacodynamics. Exploratory endpoints are quality of life and/or cancer-related pain. Statistical methods and target accrual The trial has 85% power to detect a PFS HR of 0.64 with two sided α = 0.05. The hypothesized median PFS is 4.0 months for capecitabine and 6.25 months for GV. Target accrual is open for 300 pts. Citation Format: Melisko M, Yardley DA, Blackwell K, Forero A, Ma C, Montero A, Daniel BR, Wright G, Fehrenbacher L, Chew H, Ferrario C, Nanda R, Seiler Jr M, Guthrie T, Vance K, Ouellette G, He Y, Bagley RG, Zhang J, Vahdat LT. The METRIC trial: A randomized international study of the antibody-drug conjugate glembatumumab vedotin (GV or CDX-011) in patients with metastatic gpNMB-overexpressing triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-15.

Abstract OT2-6-16: A pivotal multicenter, randomized, study evaluating the novel antibody-drug conjugate CDX-011 in patients with metastatic, triple-negative, high GPNMB over-expressing breast cancer

Abstract Background: GPNMB is an internalizable transmembrane glycoprotein overexpressed in multiple tumor types where it is a poor prognostic factor. Its functions appear to include mediating intercellular adhesion, promoting tissue repair, and regulating cell growth and differentiation. In tumor cell lines including breast cancer (BC), GPNMB enhances tumor growth and bone metastases. Relative to other BC subtypes, triple-negative BC (TNBC) highly over-expresses GPNMB in tumor epithelium where it correlates with a higher risk of recurrence. CDX-011 (glembatumumab vedotin) is a fully human GPNMB-specific monoclonal antibody drug conjugate combining the tumor-targeting GPNMB antibody with the potent cytotoxic microtubule inhibitor, monomethylauristatin E (MMAE). In the Phase II EMERGE study, 122 patients (pts) with heavily pre-treated BC (2-7 priors) and GPNMB-expression by IHC in ≥ 5% of either the tumor epithelial or stromal cells in archival tissue were randomized 2:1 to receive CDX-011 or “investigator's choice” (IC) single-agent chemotherapy, with crossover to CDX-011 permitted. CDX-011 as compared to IC, demonstrated higher objective response rates, with ORR of 8/25 (32%) vs 1/8 (13%) for high GPNMB expression (defined as expression in ≥25% of epithelial tumor cells) and 5/27 (19%) vs. 0/9 (0%) for TNBC. In the presence of both TNBC and high GPNMB, ORR was 4/12 (33%) vs 0/4 (0%) which corresponded to a doubling of median progression-free survival (PFS, p = 0.008) and median overall survival (OS, p = 0.003). CDX-011 was well tolerated with less hematologic toxicity (neutropenia: 29% vs 44%; leukopenia: 10% vs 27%; thrombocytopenia: 4% vs. 15%) but more rash (47% vs. 2%) and neuropathy (23% vs 12%) than IC. Methods: The current pivotal study aims to evaluate CDX-011 in metastatic GPNMB-over-expressing TNBC defined as ER and PR &amp;lt; 1%, HER2 negative (0-1+ IHC, or FISH ratio &amp;lt; 1.8). Eligibility criteria include &amp;gt;25% tumor epithelium GPNMB expression by central IHC; taxane and anthracyline resistance; ≤1 prior chemotherapy regimen for advanced BC; measurable disease by RECIST 1:1 and no persistent treatment-related toxicity of ≥ Grade 2 severity. 300 pts will be randomized (2:1) to receive CDX-011 (1.88 mg/kg IV q 21 days) or capecitabine (2500 mg/m2 daily for d1-14, q21 days) until progression or toxicity. Disease assessments are performed every six weeks for 6 months, and every 12 weeks thereafter. All pts are subsequently followed for survival. Endpoints are ORR and PFS (co-primary), duration of response, OS, safety, pharmacokinetics, and quality of life; tumor response assessments will be assessed by central review per RECIST 1.1. The trial has 80% power to detect a hazard ratio of 0.64 for PFS with α = 0.01 and/or a 30% increase in ORR (from 15% to 30%) with α = 0.04. For further information, contact info@celldextherapeutics.com. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-6-16.

Trade-offs in quality of life and survival with chemotherapy for advanced breast cancer: mature results of a randomized trial comparing single-agent mitoxantrone with combination cyclophosphamide, methotrexate, 5-fluorouracil and prednisone.

BackgroundWe evaluate trade-offs between quality of life (QoL) and survival improvement for two chemotherapy regimens in advanced breast cancer. We also report on the long-term survival of patients in the ANZ 8614 clinical trial.MethodsA total of 391 patients were randomized to mitoxantrone (14 mg/m2 intravenously every 21 days) or a combination of cyclophosphamide 100 mg/m2 and prednisone 40 mg/m2 orally days 1 to 14 plus methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 intravenously days 1 and 8 every 28 days (CMFP). QoL was self-assessed on 14 linear analog scales. We computed the mean differences between the two treatments as products of the mean differences in global QoL, progression-free survival and overall survival.ResultsCMFP led to a higher overall tumor response (39% vs. 25%, P=0.004) and longer progression-free survival (PFS) (median 5.6 vs 3.9 months, P=0.02) but with significantly more toxicity from alopecia, mucositis, diarrhea, anemia and lethargy. Overall survival (OS) was similar in the two groups (median 10.1 vs 11.6 months, P=0.81). QoL over the first 12 weeks was rated better by patients on CMFP for mood (P=0.04), nausea and vomiting (P=0.01), and feeling sick (P=0.02) but worse for hair loss (P<0.0001). A weighted combination of individual QoL items favoured CMFP (subset score mean difference 2.4, P=0.03). A global QoL score tended to favour CMFP (global score mean difference 1.7, P=0.18). Quality-adjusted PFS was significantly longer with CMFP (mean 7.208 vs 5.965 months, P=0.04), but quality-adjusted OS was not significantly different (mean 11.832 vs 11.315 months, P=0.57).ConclusionDespite the greater toxicity, the superior antitumor activity of CMFP led to an overall improvement in quality-adjusted PFS. In advanced breast cancer, in clinical decision making about treatment for palliative intent, the principle used to assess trade-offs between antitumor efficacy and toxicity remains relevant and applicable to all modern therapeutic agents.

Phase II study of intravenous vinflunine after failure of first-line vinorelbine based regimen for advanced breast cancer

PurposeThis open label phase II study evaluated the safety and efficacy of vinflunine in patients with breast cancer previously treated with a vinorelbine-based regimen and who progressed during or within 6 months of completing this chemotherapy. Patients and methodsThirty eight patients received vinflunine 320 mg/m2 once every 3 weeks. The primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. ResultsORR was 8.3% (95% CI: 1.75–22.4) and DCR was 75% (95% CI: 57.8–87.9). PFS was 4.0 months (95% CI: 2.5–6.1) and OS was 13.6 months (95% CI: 8.7–18.9).Toxicities not hampering dose intensity were as expected neutropenia (75.6% of patients), fatigue (44.7%), constipation (28.9%) and abdominal pain (26.3%). ConclusionVinflunine demonstrated antitumour activity and can be safely administered in breast cancer patients refractory/resistant to vinorelbine.

Abstract 2706: Phase 2 study with pharmacokinetics (PK) analysis of sorafenib and vinorelbine in metastatic breast cancer

Abstract Background Sorafenib (S) is an oral inhibitor of the Raf, VEGFR and PDGFR pathways that contribute to chemoresistance in cancer cells. The combination of S with chemotherapy agents (capecitabine, paclitaxel) in metastatic breast cancer (BC) resulted in improved progression-free survival. In preclinical models of BC, favorable effects were noted combining S and vinorelbine (V). S and V are both metabolized through hepatic isoenzymes CYP3A, with the potential of PK interactions. A previous phase 1b study documented the feasibility of this combination. We aimed to define the activity and safety of this regimen in advanced BC and to investigate PK interactions of the 2 drugs at full doses. Methods Eligible patients were affected by Her2 negative, chemotherapy-naive metastatic BC, with measurable (RECIST) disease, adequate renal, liver and bone marrow functions and LVEF Δ50%. Treatment included V (30 mg/m2 days 1, 8 every 21) + S (400 mg bid continuously), with dose reductions for grade 2-4 toxicities. Patients still benefiting after 8 cycles of treatment could continue on single-agent S. Six patients underwent PK analysis, starting treatment with S on day 4 of the first cycle, allowing for comparison of PK of each agent (V and S) administered alone versus during concomitant treatment with the other agent. Results 27 evaluable patients started on treatment, median age 57 (35-78); they received a median of 8 cycles to date (1-28), with 4 patients still on treatment. 44% of patients required at least one dose reduction for toxicity. One patient died of complicated sepsis after febrile neutropenia. Other significant toxicities included: febrile neutropenia (8%), uncomplicated Grade 3 (G3)-G4 neutropenia (60%); G3 fatigue (20%), hand-foot syndrome (12%), diarrhea (4%), enteritis (4%), hypertension (4%), asymptomatic increase of AST/ALT (16%), amylase (12%), lipase (8%), GGT (4%); G2 decrease in LVEF (4%), rash (16%), alopecia (20%). 33% of patients had a partial response, 85% experienced a clinical benefit (including stable disease after at least 4 cycles of treatment). Median progression-free survival was 5.5 months (95% CI 4.6-7.5). PK analysis showed no statistically significant interaction between S and N. Also the conversion of S to its metabolite S-N-oxide was not affected by the concomitant treatment with V. A non-significant trend was noticed for higher Cmax/AUC of V in the first 30 minutes after infusion when administered with ongoing treatment with S. Conclusions Combining S with V is feasible, but not devoid of toxicity, for which frequent dose reductions are necessary. A PK interaction could not be ruled out with the small sample size analyzed. More frail patients should start at a lower dose of both agents and we recommend close monitoring for the first 2 cycles, including amylase and lipase. Promising efficacy of this combination was observed, with a very high rate of disease control. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2706. doi:1538-7445.AM2012-2706

OT3-01-09: Phase 3 Trial Comparing Capecitabine in Combination with SorafenIb or Placebo for Treatment of Locally Advanced or Metastatic HER2−Negative Breast Cancer (RESILIENCE).

Abstract Sorafenib (SOR) is an oral multikinase inhibitor with antiangiogenic and antiproliferative activity. SOR is currently indicated for renal cell and hepatocellular carcinoma, with indications in other tumor types being explored. In a double-blind, randomized phase 2b screening trial (SOLTI-0701) in patients with advanced HER2−negative breast cancer (BC), the addition of SOR to capecitabine (CAP) showed a statistically significant improvement in the primary endpoint of progression-free survival (PFS) compared with placebo (PL)+CAP (median 6.4 vs 4.1 mo; hazard ratio=0.58; 1-sided P=0.0006). The combination was tolerable. Grade 3/4 adverse events were comparable between treatment arms with the exception of grade 3 hand-foot skin reaction/syndrome (HFSR/HFS) (44% in SOR+CAP vs 14% in PL+CAP). The SOLTI-0701 results indicate a potential role for the oral combination of SOR+CAP in the treatment of BC and support a phase 3 trial. Design: RESILIENCE is an ongoing multinational, double-blind, PL-controlled, randomized phase 3 trial designed to assess SOR+CAP as a first- or second-line therapy in advanced HER2−negative BC. Eligibility criteria include: ≥18 years of age; ≤1 prior chemotherapy regimen for advanced BC; and resistant to/failed taxane and anthracycline or no indication for further anthracycline treatment. Prior hormonal or radiation therapy is allowed, but prior use of VEGF inhibitors is not. Patients with significant cardiovascular disease or active brain metastases are not eligible. Patients are stratified by hormone receptor status, geographic region, and prior chemotherapy for advanced BC and randomized (1:1) to CAP (1000 mg/m2 po twice daily [BID], days 1–14 of a 21-day cycle) in combination with SOR (po BID, days 1–21, total dose 600 mg/day) or matching PL. CAP and SOR/PL doses can be escalated to 2500 mg/m2 per day and 800 mg/day, respectively, as tolerated. The protocol outlines strategies to manage toxicities with dose interruption and reduction. Dose re-escalation after reduction is allowed for SOR/PL (per protocol guidance) but not for capecitabine. Guidelines are provided for prophylactic and symptomatic treatment of HFSR/HFS. Radiographic assessment is every 6 wk for the first 36 wk, and every 9 wk thereafter. The primary endpoint is PFS. Assuming a 1-sided alpha of 0.005 and a power of 98.9%, the sample size is estimated at ∼519 patients, with primary analysis planned after 363 events. Secondary endpoints include overall survival, time to progression, overall response rate (RECIST 1.1 criteria), duration of response, and safety. In addition, patient reported outcomes will be assessed, and the trial will include an exploratory analysis of biomarkers. Enrollment began in Nov 2010. The trial is registered at ClinicalTrials.gov (NCT01234337). Conclusions: RESILIENCE will provide definitive PFS data for SOR+CAP as a first- or second-line therapy in HER2−negative locally advanced or metastatic BC. The phase 3 design and improved dosing guidance since SOLTI-0701 will better characterize the benefit-to-risk profile of this regimen. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-09.

Abstract C23: Phase 3 trial comparing capecitabine in combination with sorafenib or placebo for treatment of locally advanced or metastatic HER2-negative breast cancer (RESILIENCE).

Abstract Background: Sorafenib (SOR) is an oral multikinase inhibitor with anti-angiogenic and antiproliferative activity. SOR is currently indicated for renal cell and hepatocellular carcinoma, with activity in other tumor types being explored. In a double-blind, randomized phase 2b screening trial (SOLTI-0701) in patients with advanced HER2-negative breast cancer (BC), a statistically significant improvement in the primary endpoint of progression-free survival (PFS) was seen for SOR + capecitabine (CAP) compared with placebo (PL)+CAP (median 6.4 vs 4.1 mo; hazard ratio=0.58; 1-sided P=0.0006). The toxicity profile of the combination was manageable. Grade 3/4 adverse events were comparable between treatment arms with the exception of Grade 3 hand-foot skin reaction/syndrome (HFSR/HFS) (44% in SOR+CAP vs 14% in PL+CAP). The SOLTI-0701 results indicate a potential role for the oral combination of SOR+CAP in the treatment of BC and support a phase 3 trial. Design: RESILIENCE is an ongoing multinational, double-blind, PL-controlled, randomized phase 3 trial designed to assess SOR+CAP as a first- or second-line therapy in advanced HER2-negative BC. Eligibility criteria include: ≥18 years of age; ≤1 prior chemotherapy regimen for advanced BC; and resistant to/failed taxane and anthracycline or no indication for further anthracycline treatment. Prior hormonal or radiation therapy is allowed, but prior use of VEGF inhibitors is not. Patients with significant cardiovascular disease or active brain metastases are not eligible. Patients are stratified by hormone receptor status, geographic region, and prior chemotherapy for advanced BC and randomized (1:1) to CAP (1000 mg/m2 po twice daily [BID], days 1–14 of a 21-day cycle) in combination with SOR (po BID, days 1–21, total dose 600 mg/day) or matching PL. SOR 600 mg/day corresponds to the average daily dose during SOLTI-0701 that was effective and manageable. CAP and SOR/PL doses can be escalated to 2500 mg/m2 per day and 800 mg/day, respectively, as tolerated. The protocol outlines strategies to manage toxicities with dose interruption and reduction. Dose re-escalation after reduction is allowed for SOR/PL (per protocol guidance) but not for capecitabine. Guidelines are provided for prophylactic and symptomatic treatment of HFSR/HFS. Radiographic assessment is every 6 wks for the first 36 wks, and every 9 wks thereafter. The primary endpoint is PFS. Assuming a 1-sided alpha of 0.005 and a power of 98.9%, the sample size is estimated at ∼519 patients, with primary analysis planned after 363 events. Secondary endpoints include overall survival, time to progression, overall response rate (RECIST 1.1 criteria), duration of response, and safety. In addition, patient-reported outcomes will be assessed, and the trial will include an exploratory analysis of biomarkers. Enrollment began in Nov 2010. The trial is registered at ClinicalTrials.gov (NCT01234337). Conclusions: RESILIENCE will provide definitive PFS data for SOR+CAP as a first- or second-line therapy in HER2-negative locally advanced or metastatic BC. The phase 3 design and improved dosing guidance since SOLTI-0701 will allow benefit-to-risk profile of this regimen to be better characterized. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C23.

Abstract P6-12-02: A Randomized Phase II Study of Sunitinib vs. Standard of Care for Patients with Previously Treated Advanced Triple-Negative Breast Cancer

Abstract Background Triple-negative (TN) breast cancer (BC), which comprises approximately 15% of all BC cases, has a particularly poor prognosis. In a phase II study in patients with heavily pretreated metastatic BC, 15% of patients (3/20) with TN disease achieved PRs following treatment with the multitargeted tyrosine kinase inhibitor sunitinib. A randomized, open-label phase II study was conducted to compare the PFS obtained with sunitinib monotherapy and single-agent standard-of-care (SOC) chemotherapy in patients with previously treated advanced TNBC, results of which are reported here. MethodsEligible patients (≥18 years, ECOG PS 0-2) with advanced ER/PR/HER2- negative BC had been treated with an anthracycline and a taxane in the adjuvant or advanced setting; if disease-free &amp;gt;6 months post-adjuvant therapy, patients should have received 1-2 prior chemotherapy regimens for advanced BC. Patients were randomized (1:1) to receive either sunitinib 37.5 mg po daily or the investigator's choice of SOC therapy (capecitabine: 2,000-2,500 mg/m2 po days 1-14 q3w; vinorelbine: 25-30 mg/m2 IV or 60-80 mg/m2 po qw; docetaxel: 75-100 mg/m2 IV q3w; paclitaxel: 175-200 mg/m2 IV q3w or 80-90 mg/m2 IV qw or qw3/4; or gemcitabine: 800-1,250 mg/m2 IV qw2/3). Patients with documented disease progression per RECIST in the SOC arm were offered sunitinib therapy. The primary endpoint was PFS as assessed by independent central review; secondary endpoints included RECIST-defined ORR, OS, and safety. Log-rank tests were used to compare treatment arms for time-to-event endpoints. Results At data cut-off (April 1, 2010), the ITT population comprised 217 female patients (sunitinib: 113; SOC: 104). Based on independent central review, median PFS was 2.0 months in the sunitinib arm and 2.7 months in the SOC arm (HR: 1.20; 95% CI: 0.89-1.63; 1-sided P=0.889). Likewise, sunitinib did not prolong median OS, which was 9.4 months in the sunitinib arm and 10.5 months in the SOC arm (HR: 1.22; 95% CI: 0.89-1.68; 1-sided P=0.892). The ORR was 3% with sunitinib and 7% with SOC (odds ratio: 0.37; 95% CI: 0.06-1.70; 1-sided P=0.963). The most frequent grade 3/4 AEs of any cause were neutropenia (21%), thrombocytopenia (11%), asthenia (10%), and leucopenia (10%) in the sunitinib arm and neutropenia (11%), fatigue (5%), and hand-foot syndrome (5%) in the SOC arm. Treatment was discontinued due to AEs in 35% and 6% of patients in the sunitinib and SOC arms, respectively. Conclusions The study did not meet its primary or secondary endpoints, as sunitinib did not improve PFS, OS, or ORR compared with SOC therapy. Based on these results, sunitinib monotherapy is not recommended for treatment of patients with previously treated advanced TNBC. There remains an urgent need for effective treatments for patients with TNBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-12-02.

Multivariate analysis (MVA) of progression-free survival (PFS) in two phase IIb, multinational, double-blind, randomized, placebo (PL)-controlled trials evaluating sorafenib (SOR) plus standard chemotherapy in patients (pts) with HER2-negative locally advanced or metastatic breast cancer (BC).

1073 Background: Two phase IIb trials in pts with advanced BC demonstrated activity for SOR plus standard chemotherapy for the primary endpoint of PFS. In Study A, median PFS for SOR + capecitabine (CAP) versus PL+CAP was 6.4 versus 4.1 mo (hazard ratio [HR] 0.58; 1-sided p=0.0006). In Study B, median PFS for SOR + paclitaxel (PAC) versus PL+PAC was 6.9 versus 5.6 mo (HR 0.79; 1-sided p=0.09). In both studies, randomization was stratified by visceral status with slight imbalances in some covariates. We performed MVA to assess the impact of imbalances and prognostic factors on PFS. Methods: Study A: Pts (N=229) with ≤1 prior chemo regimen for advanced BC were randomized to CAP (1,000 mg/m2 po, twice daily [BID], 14 of 21 days) + SOR (400 mg po, BID) or PL. Study B: Pts (N=237) with no prior chemo for advanced BC were randomized to PAC (90 mg/m2/wk IV, 3 wk on/1 wk off) + SOR (400 mg po, BID) or PL. MVA: Cox proportional hazards models of PFS stratified by visceral status were used for each study. Additiona...

Phase I Study of Nonpegylated Liposomal Doxorubicin plus Trastuzumab in Patients with HER2-Positive Breast Cancer

Background This was an open-label, nonrandomized, multicenter, 2-stage phase I trial of safety and preliminary efficacy of nonpegylated liposomal doxorubicin (NLD) in combination with trastuzumab in advanced breast cancer, with emphasis on cardiac toxicity. Patients and Methods Forty patients (median age, 48 years; range, 30–74 years) with HER2/ neu 2+ or 3+ tumors (by immunohistochemistry) were recruited December 1999 to November 2002. Patients were eligible if they received ≤ 1 previous trastuzumab regimen, ≤ 2 cytotoxic regimens for advanced breast cancer, and lifetime cumulative anthracycline doses ≤ 240 mg/m 2. The study regimen comprised NLD 60 mg/m 2 every 3 weeks and trastuzumab loading dose 4 mg/kg followed by 2 mg/kg weekly. Treatment cycles lasted 21 days. Clinical cardiac assessments were performed with multigated acquisition scans every 2 cycles. Patients were evaluated for cardiac toxicity after receiving ≥ 1 cycle. Cardiac safety was assessed after completing ≥ 4 full treatment cycles. Results Thirty out of 40 patients (75%) received ≥ 4 treatment cycles and were evaluable for cardiac safety. Five patients (13%), 4 who were doxorubicin pretreated, developed left ventricular ejection fraction reductions to < 50%, and 2 (5%) of these patients experienced clinical cardiac toxicity. Fifty percent of the patients had objective tumor responses; median progression-free survival was approximately 21 weeks. Twenty-six patients (65%) had grade 3/4 neutropenia; 2 patients experienced febrile neutropenia. Conclusion Nonpegylated liposomal doxorubicin plus trastuzumab is active in HER2-positive patients with advanced breast cancer and is associated with a lower risk of cardiac toxicity than conventional doxorubicin plus trastuzumab.

How neoadjuvant trastuzumab offers attractive regimen for advanced breast cancer

How neoadjuvant trastuzumab offers attractive regimen for advanced breast cancer

A phase I study of vandetanib and metronomic chemotherapy in advanced breast cancer.

Abstract Abstract #906 Background: Vandetanib (V) is an oral tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptors 2 and 3 and epidermal growth factor receptor. Metronomic chemotherapy, continuous low-dose oral cyclophosphamide and methotrexate (CM), has activity in combination with anti-angiogenic treatments. We sought to define the safety and tolerability of all-oral combination therapy with V and CM in advanced breast cancer.&amp;#x2028; Patients and Methods: Eligible patients (pts) had stage IV breast cancer; measurable disease was not required and stable brain metastases were acceptable. Up to 4 prior chemotherapy regimens were allowable, as was prior bevacizumab. Pts with systemic anticoagulation or QTc abnormalities were excluded. Three sequential dose escalation cohorts of approximately 8 pts were enrolled. All pts received CM (C 50 mg PO qd, M 2.5 mg PO d1-2 q week), and V in 3 dose-escalation cohorts: 100 mg qd (Cohort 1), 200 mg qd (Cohort 2), and 300 mg qd (Cohort 3). Pts received V + CM until progression or unacceptable toxicity; dose adjustments were made for treatment related toxicity. The primary endpoint was safety and toxicity of the regimen; secondary endpoints included response rate, non-invasive vascular analysis of hypertension, and platelet proteomics.&amp;#x2028; Results: 24 pts (median age 49 years) entered the study. 83% had visceral disease, 92% had received prior chemotherapy for metastatic disease (median number of regimens, 2), and 38% had received prior bevacizumab. Median cycles of therapy completed was 2 (range 1-8); median number of weeks on study was 8 (range 2-33). Toxicities in Cohorts 1 and 2 were generally manageable, and most commonly consisted of diarrhea, nausea, fatigue, abnormal hepatic function, and hyperglycemia. Despite fewer cycles of drug exposure, increased toxicity was observed in Cohort 3, including 3 episodes of dose limiting toxicity (mucositis/rash, 1; abnormal hepatic function, 2). One-third of pts required V dose reduction, and 21% of pts came off study for toxicities including cerebrovascular event (1), pulmonary embolus (1), rash (1), abnormal hepatic function (1), and myocarditis (1). Moderate hypertension was observed in 42% of pts, with a single grade 3 event. Of the 20 response-evaluable pts, 2 (10%, 95% CI 1.2 – 31.7 %) demonstrated partial response, one lasting over 30 weeks, and 3 had stable disease &amp;gt; 24 wks (15%, 95% CI 3.2 – 37.9%). Results from correlative vascular hypertension analyses and platelet proteomics will be presented.&amp;#x2028; Conclusions: The all-oral regimen of V + CM was tolerable at a maximum dose of V 200 mg qd. Dose-limiting toxicity was seen in the V 300 mg cohort. Modest clinical activity in this heavily pretreated population was observed, and supports further investigation of this anti-angiogenic regimen in advanced breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 906.

Phase III Trial Comparing Three Doses of Docetaxel for Second-Line Treatment of Advanced Breast Cancer

To evaluate whether a relationship exists between docetaxel dose and clinical response in the treatment of patients with advanced breast cancer. Patients whose cancer had progressed after one prior chemotherapy regimen for advanced breast cancer or had recurred during or within 6 months of adjuvant chemotherapy were randomly assigned to docetaxel 60, 75, or 100 mg/m2 intravenously every 3 weeks. Five hundred twenty-seven patients were randomly assigned (intent to treat [ITT]), and 524 were assessable for toxicity. In the population assessable for efficacy (n = 407), logistic regression analysis showed that increasing docetaxel dose was significantly associated with higher response rate (P = .007) and improved time to progression (TTP; P = .014). In the ITT analysis, a significant dose-response relationship was observed for tumor response (P = .026) but not for TTP (P = .067). The incidences of most hematologic and nonhematologic toxicities were related to increasing dose, with grade 3 to 4 neutropenia occurring in 76.4%, 83.7%, and 93.4% and febrile neutropenia occurring in 4.7%, 7.4%, and 14.1% of patients administered the 60, 75, and 100 mg/m2 doses, respectively. One death was considered treatment related. A relationship between increasing dose of docetaxel and increased tumor response was observed across the dose range of 60 to 100 mg/m2 every 3 weeks. Toxicities were related to increasing dose. Depending on the therapy goal, any of the doses studied may be appropriate for second-line treatment of advanced breast cancer.

Trastuzumab and vinorelbine or taxane chemotherapy for HER2+ metastatic breast cancer: The TRAVIOTA study

650 Background: The optimal trastuzumab/chemotherapy regimen for advanced breast cancer is not known. We performed a multicenter, randomized clinical trial to compare TRastuzumab And VInorebline Or TAxane (TRAVIOTA) chemo- and bio-therapy combination treatment given on a weekly schedule for HER2+ metastatic breast cancer. Patients and Methods: Eligible patients had stage IV breast cancer, measurable disease (by RECIST criteria), HER2+ tumors (IHC 3+ or FISH+), no prior chemotherapy or trastuzumab for advanced breast cancer, and LVEF &gt; 50%. Patients were randomized 1:1 to trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly thereafter) with either weekly vinorelbine (25 mg/m2) or weekly taxane (paclitaxel 80 mg/m2 or docetaxel 35 mg/m2, selected by the treating investigator). The primary endpoint was response rate. The study opened in August 2001 and planned to accrue 250 patients. It was closed in December 2003 having accrued only 85 patients. Results are presented for the 81 patients who received any protocol-based therapy. Results: Patients receiving trastuzumab and vinorelbine tended to have higher response rates and TTP than those assigned trastuzumab and taxane therapy but the results were not statistically significant (see Table ). Vinorelbine therapy was associated with more frequent grade 3 or 4 hematological toxicity and dose delay because of myelosuppression. Other toxicities generally reflected the known side effects of the chemotherapy agents. Conclusions: The TRAVIOTA study suggests at least comparable clinical activity of trastuzumab with vinorelbine as with weekly taxane chemotherapy in HER2+ metastatic breast cancer, with side effect profiles consistent with previous experience with these regimens. [Table: see text] [Table: see text]

Mitomycin C, vinblastine and cisplatin (MVP): an active and well-tolerated salvage regimen for advanced breast cancer

This phase II study assessed the clinical efficacy and tolerability of a combination of mitomycin C, vinblastine and cisplatin in patients with metastatic breast cancer (MBC) previously treated with chemotherapy. A total of 87 patients with MBC, most of whom had been exposed to anthracyclines (92%) and/or taxanes (29%) in the adjuvant and/or metastatic setting, were treated with mitomycin C (8 mg m−2 day 1 cycles 1, 2, 4 and 6), vinblastine (6 mg m−2 day 1) and cisplatin (50 mg m−2 day 1) repeated each 21 days for a maximum of six cycles. The overall response rate (ORR) was 32% (95% CI: 22–42%) with 31% partial response (PR) and one complete response (CR). Stable disease (SD) rate was 21% (95% CI: 12–29%). There was no statistically significant difference in the ORR when MVP was given as the first-line treatment for MBC vs second or subsequent line (38 vs 30%, P=0.6), or between patients with an early (<6 months) vs late (>6 months) relapse post-anthracyclines (30 vs 52%, P=0.3). Toxicity profile was mild. This platinum-based chemotherapy is an effective, well-tolerated and low-cost regimen for patients with MBC, including those pretreated with anthracyclines.