A multicenter phase I-II trial of weekly paclitaxel and carboplatin plus bevacizumab in women with triple-negative metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1045-1045
Author(s):  
Emmanouil S. Saloustros ◽  
Aristidis Polyzos ◽  
Charalampos Christophyllakis ◽  
Nikolaos K. Kentepozidis ◽  
Lampros Vamvakas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Objective Response Rate ◽  
Triple Negative ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Dna Breaks ◽  
Grade 3

1045 Background: Triple-negative breast cancer cells are unable to repair double stranded DNA breaks and hence have sensitivity to platinum agents. The combination of carboplatin and paclitaxel administered weekly is active and well tolerated. Bevacizumab when added to paclitaxel prolonged progression-free survival in metastatic breast cancer (MBC). We investigated the activity and toxicity of paclitaxel plus carboplatin and bevacizumab in triple-negative MBC. Methods: The study’s primary objective was to estimate the objective response rate [complete (CR) + partial remission (PR)] and toxicity of the combination in women with triple negative MBC who had no prior chemotherapy for metastatic disease. The study followed the Simon's two-stage optimal design with 16 patients initially evaluated for response and toxicity and then expanding to a total of 46 patients. The null hypothesis that the objective response rate is ≤40% could be rejected if the number of CR/PR was ≥23. Paclitaxel 90mg/m2and Carboplatin AUC 2 were administered on days 1, 8, and 15 every 4 weeks, preceded by bevacizumab 10 mg/kg on days 1 and 15. Results: 45 women with triple negative MBC have been recruited thus far. Of them, 12 were premenopausal and 27 had prior (neo-)adjuvant chemotherapy. The median cycles administered were 5 (range 1-8). Of 38 evaluable patients we observed 7 CR, 22 PR’s for an objective response rate 76%. Seven patients achieved stable disease, while two had disease progression. Median duration of response was 8.1 months with median time to progression 9.2 months. Neutropenia grade 3 and 4 was experienced by 13 and 6 patients, respectively, with one toxic death due to febrile neutropenia. Other grade 3 toxicities included anemia/neurotoxicity (n=2), thrombocytopenia/diarrhea (n=1). Conclusions: Although still ongoingthe study has achieved the primary objective of demonstrating clinical activity for weekly carboplatin and paclitaxel in combination with bevacizumab in triple negative MBC. We believe that this triplet combination merits further evaluation in this patient population for whom there is no standard treatment. Clinical trial information: NCT00691379.

Pegylated liposomal doxorubicin (PLD) with cyclophosphamide (C) as 1st-line chemotherapy for metastatic breast cancer (MBC) patients previously treated with adjuvant anthracyclines

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10627-10627 ◽  
Author(s):  
T. A. Vandenberg ◽  
M. Trudeau ◽  
L. Provencher ◽  
L. C. Panasci ◽  
L. Yelle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Median Time ◽  
Clinical Benefit ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Exposure Limits ◽  
Grade 3

10627 Background: Anthracyclines (A) are key elements in adjuvant and metastatic chemotherapy regimens for breast cancer. Pre-exposure limits the utilization of A in advanced disease due to cumulative cardiotoxicity. PLD (Caelyx/Doxil) has equivalent activity to conventional doxorubicin in MBC. However PLD has reduced toxicity, including significantly less cardiotoxicity. Combinations of A+C are the backbone of many adjuvant therapies, thus C represents a logical drug to combine with PLD. Methods: MBC patients with measurable disease who completed anthracycline containing adjuvant therapy > 12 months ago were entered in a multi-center single arm phase II trial. They received PLD 35mg/m2 + cyclophosphamide 600 mg/m2 every 3 weeks. This study was powered to demonstrate an objective response rate > 25%. Results: Seventy three patients were enrolled. Prior adjuvant therapy included: AC (37%), CEF/FEC (28%), AC-T (15%), AT (7%), EC (7%). The median cumulative dose of prior A were 240mg/m2 and 580mg/m2 for doxorubicin or epirubicin, respectively. Median time since adjuvant chemotherapy was 4.4 years (1–14). Patients received a median of 6 cycles (2–10) of PLD + C. Major toxicities were; grade 3/4 neutropenia (7.5%), asymptomatic > 10% declines in LVEF (9%) (reversible upon discontinuation of PLD), grade 3/4 hand foot syndrome (6%). Other toxicities were uncommon and usually did not require discontinuation. The objective response rate (ORR) was 38% (4% CR and 34% PR), with an additional 32% having stable disease > 6 months for a clinical benefit of 70% (CB). ORR was similar for patients who had received adjuvant taxanes. Kaplan-Meyer estimated median time to progression was 31.5 weeks (23% progression free). Conclusions: The combination of PLD + C every 3 weeks in patients who have completed adjuvant anthracycline chemotherapy after more than one year prior is well tolerated and has a clinical benefit rate of 70%. This finding is similar to other commonly employed chemotherapeutic regimens for MBC and suggests that re-treatment with a non-cardiotoxic anthracycline following previous anthracycline therapy may be a reasonable therapeutic option for some patients. [Table: see text]

Bevacizumab and albumin-bound paclitaxel treatment in metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1101-1101 ◽  
Author(s):  
J. S. Link ◽  
J. R. Waisman ◽  
B. Nguyen ◽  
C. I. Jacobs
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Stable Disease ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Brain Lesion ◽  
Metastatic Breast ◽  
Significant Activity ◽  
Pet Ct

1101 Background: Miller, et al demonstrated the combination of bevacizumab and paclitaxel has significant activity in metastatic breast cancer. Because paclitaxel albumin bound (PAB) has been shown to have less toxicity, a better tumor delivery and possibly better response for metastatic breast cancer, we combined it with bevacizumab (B) to treat women with metastatic breast cancer. Methods: This is a retrospective analysis. Billing records from March 2005 through December 2006 were reviewed to obtain all patients treated consecutively with a combination of PAB (80–125mg/m2 days 1,8,15 or 170–200 mg/m2 every 14 days on a 28 day cycle) and B (10mg/kg every 14 days). A total of 40 women were identified. A minimum of two courses were given. All women had received a minimum of 3 prior chemotherapy regimens including anthracyclines 34/40 and taxanes 35/40. Patients were monitored for response using RECIST criteria based on PE, and PET/CT imaging. Six women with bone only disease were monitored with PET, CT/MRI and tumor markers. All response data were confirmed by independent review. Results: 20 women had objective responses to the PAB/B regimen (3CRs and 17PRs) for an overall response rate of 50%. Another seven women had stable disease (SD) for a mean duration of 212 days. Thirteen women progressed. The mean time to progression for the responders was 132 days. Toxicity was acceptable with fatigue (9 gr 2), neuropathy (4 gr 2, 1 gr 3), anemia (2 gr 2, 2 gr 3), and hypertension (3 gr 2) being the most common complaints. Two patients were discontinued due to a possible CNS hemorrhage into a metastatic brain lesion. There were no other treatment discontinuations due to non-tolerance Conclusions: In our limited series of consecutive woman with advanced, heavily pretreated metastatic breast cancer treated with PAB (Abraxane) and bevacizumab (Avastin), we saw a 50% objective response rate (3CR, 17PR). The regimen was well tolerated with acceptable toxicity. Another seven women had stable disease for an average duration of >200days giving an objective response rate + SD of 67%. No significant financial relationships to disclose.

Phase II trial of RAD001 plus carboplatin in patients with triple-negative metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11529-e11529
Author(s):  
Jasmeet Chadha Singh ◽  
Stacy Stein ◽  
Matthew Volm ◽  
Julia Anne Smith ◽  
Yelena Novik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Clinical Benefit ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Grade 3 ◽  
Platinum Agents

e11529 Background: Triple negative breast cancer cells are unable to repair double stranded DNA breaks and hence have sensitivity to platinum agents. Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of RAD001 (oral mTOR inhibitor) and Carboplatin may have activity in triple-negative breast cancer. Methods: The primary objective of the study was to estimate the clinical benefit (complete remission (CR) + partial remission (PR) + stable disease (SD) >6 months) and the toxicity of this combination in women with triple negative metastatic breast cancer who have had 0-3 prior chemotherapy regimens for metastatic disease. 25 subjects were to be entered into a single stage open label Phase II study. Prior Carboplatin is allowed. Treated brain metastasis are eligible. The null hypothesis that the clinical benefit rate is ≤10% could be rejected if number of CR/PR/SD >6 months was ≥6. Originally, intravenous Carboplatin AUC 6 was to be administered every 3 weeks along with daily 5mg of RAD001 with a 3 patient run-in and then 10 mg daily. Due to a surprising amount of thrombocytopenia with this combination, the dose of Carboplatin was first amended to AUC 5 and most recently to AUC 4 with 5 mg of RAD001. Results: 18 patients have been recruited thus far. Median age is 59. There have been 1 CR, 4 PR’s and 2 SD's lasting > 6 months. One SD was achieved in a patient progressing on single agent Carboplatin at study entry. Median duration of CR+ SD +PR thus far is 13 weeks (range: 6-60 weeks). 5 patients had grade 3/4 thrombocytopenia and 4 patients had grade 3 neutropenia (no febrile neutropenia). However, since amendment of Carboplatin dose to AUC 4 the regimen has been well tolerated. 1 patient suffered from grade 3 dehydration. The estimated clinical benefit rate is 50% (95% C.I.: 24%, 76%). Median time to progression or death is 87.5 days from start of treatment; there is only 1 death to date on this study. Conclusions: The study has achieved it’s primary objective of demonstrating clinical benefit of RAD 001-Carboplatin combination in triple negative metastatic breast cancer. Dose limiting thrombocytopenia was an unexpected side effect requiring protocol amendment.

scholarly journals Efficacy and safety of eribulin in HER2-negative metastatic breast cancer: the results of long-term experience in real clinical practice in Russia

2019 ◽  
Vol 21 (1) ◽  
pp. 12-23 ◽  
Author(s):  
Vera A Gorbunova ◽  
Irina V Kolyadina ◽  
Elena I Kovalenko ◽  
Liudmila V Manziuk ◽  
Elena V Artamonova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Practice ◽  
Triple Negative ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Disease Rate ◽  
Tumor Subtype ◽  
Efficacy And Safety

Aim. The aim of the study is to examine the efficacy and safety of eribulin in HER2-negative metastatic breast cancer (BC) in Russian clinical practice. Materials and methods. The analysis included 459 patients with advanced BC from 44 federal and municipal medical clinics in Russia and received at least 2 courses of treatment with eribulin in accordance with the registered indications for drug. The average age of women was 56 years (between 29 and 81 years), 83% of patients had HER2-negative tumor subtype (49.9% - luminal BC and 33.1% - triple-negative BC) HER2-positive biological tumor subtype was registered in 17% of patients. Visceral metastases were diagnosed in 73% of patients and three-zone and multiple zone metastases were diagnosed in 41.6% of cases. The median number of prior lines of therapy in patients with disseminated disease was 2; anthracycline and taxane chemotherapy was applied in 94.3% of patients, and 38.1% of patients were recived CT plus capecitabine. Standard treatment regimen with eribulin was cotinuing (1.4 mg/m² as a 2-5-minute intravenous infusion administrated on days 1, 8 of a 21-day cycle) until disease progression, unacceptable toxic effects, or impossibility of the drug administration for any other reason. We estimated the efficacy and safety of treatment with eribulin in Russian patients with HER2-negative BC. Results. Objective response rate was achieved in 20.5% of cases, complete response rate was in 3.2%, partial - 17.3%, and the stable disease rate was marked in 52.7% of women, and in 19.7% of these cases was prolonged more than 6 months. The frequency of objective response was higher in luminal BC group compared with triple-negative BC: 23.5% vs 15.8%; tumor growth control 76.9% vs. 67.8%, respectively; p

scholarly journals Outcome of Everolimus-Based Therapy in Hormone-Receptor-Positive Metastatic Breast Cancer Patients After Progression on Palbociclib

2020 ◽  
Vol 14 ◽  
pp. 117822342094486 ◽  
Author(s):  
Ajay Dhakal ◽  
Roby Antony Thomas ◽  
Ellis G Levine ◽  
Adam Brufsky ◽  
Kazuaki Takabe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormone Receptor ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Optimal Sequence ◽  
Hormone Receptor Positive

Background: Despite the approval of mTOR inhibitor everolimus and CDK4/6 inhibitors in the management of hormone-receptor-positive HER2 non-amplified metastatic breast cancer (HR+ HER2-MBC), the optimal sequence of therapy is unclear. There are no clinical data on efficacy of everolimus in HR+ HER2-MBC after cancer progresses on CDK4/6 inhibitors. Objective: The objective of this study is to find the efficacy of everolimus in HR+ HER2-MBC after they progress on a CDK4/6 inhibitor palbociclib. Methods: This is a retrospective, 2-institute review of HR+ HER2-MBC from Jan 2015 to March 2018 treated with everolimus after progression on palbociclib. Primary end point was median progression-free survival (PFS), secondary end points objective response rate (ORR), clinical benefit ratio (CBR), and overall survival (OS). Results: Out of 41 women with median age 61 years (33, 87) enrolled, 66% had received adjuvant systemic therapy, 61% had visceral disease, and 95% had prior nonsteroidal aromatase inhibitors. About 83% women had 3 or more chemotherapy or hormonal therapies prior to everolimus. Kaplan-Meier estimates showed a median PFS of 4.2 months (95% confidence interval [CI]: 3.2-6.2). The median OS was 18.7 months (95% CI 9.5 to not reached). Objective response rate and CBR were both 17.1%. Conclusion: Everolimus was associated with modest PFS and ORR in HR+ HER2-MBCs postprogression on palbociclib.

Phase II trial of RAD001 plus carboplatin in patients with triple-negative metastatic breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 293-293
Author(s):  
J. C. Singh ◽  
S. Stein ◽  
M. Volm ◽  
J. A. Smith ◽  
Y. Novik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Clinical Benefit ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Dna Breaks ◽  
Grade 3 ◽  
Platinum Agents

293 Background: RAD001 is an oral mTOR inhibitor that has exhibited activity in breast cancer. Triple negative breast cancer cells are unable to repair double stranded DNA breaks and hence have sensitivity to platinum agents that cause interstrand cross-links. Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in at least two different breast cancer cell lines (including ER/PR negative cell lines). We propose that combination RAD001 and carboplatin may have activity in triple-negative breast cancer. Methods: The primary objective of the study is to determine clinical benefit (complete remission; CR, partial remission; PR and stable disease; SD) and the toxicity of this combination in women with triple negative metastatic breast cancer who had received 0-3 prior chemotherapy regimens for metastatic disease. Prior carboplatin was allowed. Women with treated brain metastasis were eligible. Secondary objectives were to determine progression free survival. According to the original study plan, carboplatin AUC 6, was to be given intravenously every three weeks. 5 mg of RAD001 was to be given daily with a 3 patient run-in and then 10 mg daily if there were no dose-limiting toxicities. Due to a surprising amount of thrombocytopenia with this combination the dose of carboplatin was first amended to AUC 5 and most recently to AUC 4 with 5 mg of RAD001 (and no plan to escalate to 10 mg). Results: Eleven patients of a planned 25 have been recruited thus far. Median age is 62. Median number of prior regimens is 1. Of the 6 patients assessable for response at this time, four have SD and two have had a PR. 1 SD was achieved in a patient progressing on prior carboplatin at study entry. Five of 7 patients assessable for toxicity had grade 3 or 4 thrombocytopenia and 2 patients had grade 3 neutropenia. All patients have had treatment held and/or dose reductions secondary to hematological toxicity. There have been no non-hematological grade 3 or 4 toxicities. Conclusions: Clinical benefit was observed in all 6 evaluable patients. Dose limiting thrombocytopenia was an unexpected side effect requiring protocol amendment. We continue to accrue study subjects at the amended dosing.

Preliminary efficacy data of triple-negative breast cancer cohort of NCI 9881 study: A phase II study of cediranib in combination with olaparib in advanced solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1077-1077
Author(s):  
Navid Hafez ◽  
Hatem Hussein Soliman ◽  
Siqing Fu ◽  
Karen A. Gelmon ◽  
Albiruni Ryan Abdul Razak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Objective Response Rate ◽  
Triple Negative ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Metastatic Breast

1077 Background: Cediranib, a pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, suppresses expression of BRCA1, BRCA2, and RAD51 and increases sensitivity of tumors to poly-(ADP-ribose) polymerase (PARP) inhibitors in vitro. Olaparib, a PARP inhibitor, demonstrates clinical efficacy in patients with germline BRCA1/2 mutations and HER2-negative metastatic breast cancer. We therefore tested the anti-tumor activity of the combination of cediranib and olaparib in patients (pts) with metastatic triple-negative breast cancer (TNBC). Methods: This multi-institutional, two-stage, phase II study enrolled patients with metastatic TNBC previously treated with a minimum of one prior line of systemic therapy in the advanced setting. Patients were treated with cediranib 30mg po daily plus olaparib 200mg po BID until disease progression or unacceptable toxicity. The primary endpoint was objective response rate by RECIST v1.1. Baseline tumor biopsies were obtained for biomarker analyses. Results: Baseline characteristics of the 37pts enrolled are summarized below. The overall objective response rate was 14% (95% CI: 0.025, 0.2453). Median duration of response was 2.0 months (mos) with a range of 1.8 to 6.3 mos. Disease control rate ((# of pts with CR, PR or SD)/(# of evaluable pts)) was 81% (95% CI: 0.6846, 0.937). Median PFS was 3.7 mos (95% CI: 2.1, 4.3). Grade 3/4 adverse events (G3/4 AEs), irrespective of attribution, occurred in 25 of 38 (66%).G3/4 AEs occurring in > 5% of pts were hypertension (24%) and dyspnea (11%), diarrhea (8%) vomiting (8%). Conclusions: The cediranib/olaparib combination resulted in promising objective responses in 14% of biomarker-unselected patients with heavily pre-treated, metastatic TNBC. The regimen required prompt initiation of antihypertensives, but AEs were overall manageable. Analyses of mutation status in homologous recombination DNA repair genes are ongoing and will be correlated with clinical outcome. Clinical trial information: NCT02498613 . [Table: see text]

A phase II study of weekly nanoparticle albumin-bound paclitaxel combined with cisplatin in patients with metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11568-e11568
Author(s):  
Biyun Wang ◽  
Xi-Chun Hu ◽  
Si Sun ◽  
Jian Zhang ◽  
Lichen Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Triple Negative ◽  
Response Rate ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Primary Objective ◽  
Overall Response

e11568 Background: This prospective phase II study was to investigate the efficacy and toxicity of weekly albumin-bound paclitaxel (nab-paclitaxel) and cisplatin combination in patients with metastatic breast cancer. Methods: Females with unresectable, recurrent or metastatic breast cancer were eligible for participation. Nab-paclitaxel was administered weekly at a dose of 125 mg/m2 on d1, 8, 15, followed by cisplatin 75 mg/m2 on d1, repeated every 28 days with a maximum of 6 cycles. The primary objective was overall response rate (ORR) and the second objectives were progression free survival (PFS), safety, and overall survival (OS). Results: Seventy-three women were enrolled into this study. A total of 384 chemotherapy cycles were administered with a median of 6 cycles. A high overall response rate (67.1%) was achieved in the whole population. The highest response rate was observed in the first line patients (80.6%) and in patients who had not received taxane previously (80%). After a median follow-up of 12.8 months, the median PFS was 10.5 months. For the patients receiving first-, second- and third-line or more,median PFS was 12.3, 9.0 and 7.7 months, respectively (P=0.006). Subgroup analysis showed that the highest response rate was obtained in Her-2 positive patients, followed by patients with triple negative and luminal subtypes, yielding a response rate of 77.8%, 68.8% and 63.9%, respectively (P=0.584). The corresponding median PFS was 13.6, 12.7 and 10.0 months, respectively (P=0.83). While grade 4 neutropenia occurred in 46 patients (63.0%), febrile neutropenia occurred only in 9 patients (12.3%). Grade 3 peripheral neuropathy was an accumulated dose-limiting toxicity occurring in 19 patients (26.0%), 13 of whom had to stop chemotherapy due to no recovery to grade 2 or less within 2 weeks. Other common toxicities included alopecia, nausea, vomiting and rash. Conclusions: The results of this trial add to the clinical evidence that doublet of nab-paclitaxel and cisplatin has high efficacy and a good safety profile in treatment of patients with metastatic breast cancer. Further evaluation of this regimen in metastatic breast cancer, especially triple negative subtype, is justified.

Efficacy of RAD001/carboplatin in triple-negative metastatic breast cancer: A phase II study.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 108-108
Author(s):  
Jasmeet Chadha Singh ◽  
Matthew Volm ◽  
Yelena Novik ◽  
James L. Speyer ◽  
Sylvia Adams ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Clinical Benefit ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Dna Breaks ◽  
Clinical Benefit Rate ◽  
Grade 3 ◽  
Platinum Agents

108 Background: Triple-negative breast cancer cells are unable to repair double stranded DNA breaks and have sensitivity to platinum agents. Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. RAD001 (oral mTOR inhibitor) and Carboplatin combination may have activity in triple-negative breast cancer. Methods: The primary objective is to estimate clinical benefit (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting >6 months) and toxicity of the combination in triple negative metastatic breast cancer patients who have had 0-3 prior chemotherapy regimens. This design has > 80% power to test the null hypothesis i.e. clinical benefit rate is ≤ 10% vs. alternative hypothesis that clinical benefit rate is ≥ 30%. Prior carboplatin is allowed. Women with treated brain metastasis are eligible. Originally, carboplatin AUC 6 was to be administered every 3 weeks along with daily 5mg of RAD001 with a 3 patient run-in and then 10 mg daily. Due to a surprising amount of thrombocytopenia, the dose of carboplatin was first amended to AUC 5 and most recently to AUC 4 with 5 mg of RAD001 (no escalation to 10 mg). Results: 23 out of 25 patients have been recruited. Median age is 59. Thus far, there have been 1 CR, 5 PR’s, 8 SD's and 6 PD’s. One SD was achieved in a patient progressing on single agent carboplatin at study entry. Median duration of response is 13 weeks (range: 6-74 weeks). 5 patients had grade 3/4 thrombocytopenia and 4 patients had grade 3 neutropenia (no febrile neutropenia). 13 patients had treatment held and/or dose reductions secondary to hematological toxicity. Since dosing amendment for carboplatin to AUC 4 the regimen has been well tolerated (only 1 patient with grade 3 neutropenia and thrombocytopenia). 1 patient had grade 3 dehydration. The estimated clinical benefit rate is 45% (95% C.I.: 23%, 67%). Median time to progression or death is 85 days from start of treatment. Conclusions: Our study has met the primary end point of demonstrating clinical benefit in triple-negative metastatic breast cancer. Dose-limiting thrombocytopenia was an unexpected side effect requiring protocol amendment. Patient accrual continues at the amended dosing.

A real-world retrospective study of apatinib plus chemotherapy in metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12507-e12507 ◽  
Author(s):  
Anjie Zhu ◽  
Peng Yuan ◽  
Jiayu Wang ◽  
Fei Ma ◽  
Yang Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Clinical Benefit ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Safety Data ◽  
Metastatic Breast ◽  
Clinical Benefit Rate

e12507 Background: Antiangiogenic therapy in combination with chemotherapy has shown improved clinical outcome in advanced breast cancer(ABC). Apatinib is an orally administered tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2), which exhibited objective efficacy in metastatic breast cancer(MBC). We performed a retrospective observational analysis to evaluate the efficacy and safety of apatinib plus chemotherapy in the real-world practice of patients with MBC. Methods: Patients who have failed at least one prior chemotherapy regimen for metastatic disease were included in this study. The primary endpoint was progression free survival(PFS). Secondary end points included objective response rate(ORR), clinical benefit rate(CBR), overall survival(OS) and safety. Data analysis included association between clinicopathological characteristics or treatment choice and PFS. Results: Of the 23 patients analyzed, 14(60.9%) received plant-derived anticancer agents combined therapy and 9(39.1%) combined with non-plant-derived agents. Objective response rate(ORR) was 34.7% and clinical benefit rate(CBR) reached 52.2% on last tumor assessment. With a median follow-up of 9.0 months, the estimated median PFS and OS were 5.4 months (95%CI 3.5-7.3) and 8.2 months (95%CI 4.7-11.7), respectively. Toxicities were tolerable or could be clinically managed.The most frequently observed adverse events (AEs) of all grade were hypertension, myelosuppression, hand-foot syndrome, proteinuria, fatigue and gastrointestinal reaction. The most common grade 3/4 treatment-related AEs were myelosuppression(39.1%) and gastrointestinal reaction(17.4%). Conclusions: In this retrospective observational study, combination of apatinib with chemotherapy demonstrated clinically relevant efficacy and tolerability in metastatic breast cancer.

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