Metronomic cyclophosphamide and capecitabine combined with lapatinib in heavily pretreated metastatic breast cancer (MBC) HER2-positive patients: 2-year update.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11515-e11515
Author(s):  
Katia Cagossi ◽  
Giorgia Razzini ◽  
Alessia Ferrari ◽  
Maria Grazia Lazzaretti ◽  
Meri Leporati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Heavily Pretreated ◽  
Her 2

e11515 Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, prior systemic therapy for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression. Primary objective was time to progression (TTP) and safety. Results: Fifteenpatients were included. Median age was 52 years old (range 42-77). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 6 months (2-14). No complete response was observed. Eight out of fiftten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and were still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited significant reduction of serum marker concentrations. No grade 3-4 skin toxicity was reported. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The combination of lapatinib with metronomic chemotherapy may lead to effective palliation despite extensive pretreatment at least in bone metastatic patients. The treatment appears to be less toxic than lapatinib and capecitabine at full dosage, especially in heavily pretreated MBC patients. The preliminary results suggest the need of a clinical trial to confirm a role of this combination to delay lapatinib resistance.

Metronomic cyclophosphamide and capecitabine combined with lapatinib in heavily pretreated metastatic breast cancer (MBC) HER2-positive patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11071-e11071
Author(s):  
Katia Cagossi ◽  
Maria Grazia Lazzaretti ◽  
Alessia Ferrari ◽  
Giorgia Razzini ◽  
Meri Leporati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastases ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Breast Cancer Patients ◽  
Heavily Pretreated ◽  
Her 2

e11071 Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, measurable disease, prior systemic therapy (chemotherapy and/or hormonal therapy) for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression or unacceptable toxicity. Primary objective was time to progression (TTP) and safety. Results: Tenpatients were included. Median age was 56 years old (range 46-76). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 4 months (2-7). No complete response was observed. Six out of ten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and are still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited reduction of serum marker concentrations to normal range. No grade 3-4 toxicity was reported. There was no decline in cardiac function. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The treatment appears to be an effective and less toxic option in heavily pretreated MBC patients. Of note is the observed activity in patients with exclusive bone metastases. Monitoring of CEA and Ca15.3 during the first two months of treatment appears to provide a sensitive and economical means of identifying those patients who are responding to the therapy. Therefore, the combination of lapatinib with metronomic chemotherapy should be explored in advance for osseous MBC.

Changes in circulating endothelial cells (CEL) in patients receiving trastuzumab for metastatic breast cancer predict response to treatment

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 579-579
Author(s):  
P. Spadaro ◽  
M. Ingemi ◽  
G. Dottore ◽  
G. Toscano ◽  
R. Maisano
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Antiangiogenic Therapy ◽  
Metastatic Breast ◽  
Circulating Endothelial Cells ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Her 2

579 Background: Amplification or overexpression of HER-2/neu has been identified in 10–20% of invasive breast cancers and is associated with shorter overall survival times; furthermore HER-2/neu is a predictive factor with regard to monoclonal antibody therapy with Trastuzumab. The observed association between the overexpression of HER-2/neu and higher VEGF expression indicates that HER-2/neu is involved, at least partly, in the regulation of angiogenesis in human breast cancer. Recently circulating endothelial cells (CECs) have been proposed as a marker of tumor progression and/or a response to antiangiogenic therapy; thus, we have performed a phase II study to explore the correlation between CECs and treatment with Trastuzumab in metastatic breast cancer Methods: 22 women aged ≥ 18 years with histologically proven Her-2-positive, ECOG performance status 0 to 2 who were not eligible for, or who wished to delay receiving chemotherapy received a standard loading dose of Trastuzumab 4 mg/Kg followed by 2 mg/Kg weekly. The weekly maintenance dose was continued until disease progression. A panel of monoclonal antibodies including anti CD45 to exclude hematopoietic cells, anti CD31, CD34, CD36, CD105, CD106, CD133, and KDR and appropriate analysis gates were used to enumerate resting and activated circulating endothelial cells Results: The overall response rate (RC + RP) to treatment was 25% (2 RC + 3RP). In healthy controls (N° 20) mean values of resting and activated CECs were 7.6/μL (4.6 - 11.2/μL) and 1.3/μL (0.1 - 2.4 /μL) respectively. Before treatment with Trastuzuamb the mean resting and activated CECs were 41.1/μL (16.4 - 60.5/μL) and 6.9/μL (5.1 - 8.7/μL). At a first assessment (6 wks) a significant decrease in CECs (p<0.001)was found in patients responding to treatment but not in the patients who did not achieve a remission Conclusions: Our finding has shown that resting and activated CECs are increased in metastatic breast cancer patients and decline during treatment in responding patients, furthermore, these data underline the crucial role of angiogenesis in this setting and support the rationale for a combination of Bevacizumab with Trastuzumab. No significant financial relationships to disclose.

Activity of trastuzumab-based therapy beyond disease progression in heavily pretreated metastatic breast cancer patients—Single institution experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13159-13159
Author(s):  
P. Tokajuk ◽  
B. Czartoryska-Arlukowicz ◽  
M. Z. Wojtukiewicz
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Soft Tissues ◽  
Advanced Disease ◽  
Metastatic Breast ◽  
Second Line ◽  
Breast Cancer Patients ◽  
Heavily Pretreated ◽  
Her 2

13159 Background: Benefits from continuing trastuzumab-based (TZB) therapy beyond disease progression in HER-2-overexpressing metastatic breast cancer (MBC) patients (pts) remain obscure. Methods: A retrospective analysis was undertaken to assess activity of TZB therapy for MBC pts treated in our institution from 2002 to 2005 outside clinical trials. Results: 27 pts were evaluated. Median age: 52 years (range, 33–62). 9 pts (33.3%) were premenopausal. Hormonal receptors status: 9 pts ER(+), 4 pts PgR (+), 2 unknown. HER-2 overexpression was determined by IHC staining (3+ score) in all pts. Metastases location: 18 pts soft tissues/bone, 18 pts visceral disease. Median number of metastatic sites: 2 (range: 1–4). 9 pts (33.3%) had metastases in < 2 locations. 16 pts (59.2%) received neo/adjuvant chemotherapy: 11 pts doxorubicin, 8 pts CMF, 2 pts docetaxel, 4 pts other. Median previous chemotherapy lines for advanced disease: 2 (range: 0–6). 16 pts received doxorubicin/epirubicin, 14 pts docetaxel, 13 pts vinorelbine as a part of advanced disease chemotherapy regimen. Trastuzumab was administered at standard doses and combined with docetaxel, vinorelbine, cisplatin, capecitabine, etoposide, gemcitabine or administered as monotherapy. Response for the first-line TZB therapy was as follows: CR 5/27 pts (18.5%); PR 10/27 pts (37%). Median TTP was 5.8 months (range: 0–22). 14/27 pts (51.8%) received a second-line TZB therapy beyond disease progression. Response for the second-line therapy: CR 2/14 pts (14.3%); PR 5/14 pts (35.7%). Median TTP was 5.1 months (range: 0–24). 6/14 pts received a third-line and subsequent lines (up to five lines) of TZB therapy. PR for subsequent lines of therapy was observed in 4 pts. Median survival has not been reached. Pts who received ≥2 of TZB regimens survived significantly longer than pts who had received only 1 regimen (P = 0,02 logrank). Pts with metastasis in 1 location survived significantly longer than pts with metastasis in ≥2 sites (P = 0,01 logrank). Conclusions: Trastuzumab-based therapy seems to be active in MBC pts beyond disease progression even in heavily pretreated population. Durable responses were observed in some cases. No significant financial relationships to disclose.

scholarly journals The Difference in Clinical and Prognostic Features Between De Novo and Recurrent Her2-Positive Metastatic Breast Cancer Patients

Acta Medica ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 14-19
Author(s):  
Yusuf Acikgoz ◽  
Yakup Ergun ◽  
Gokhan Ucar ◽  
Merve Dirikoc ◽  
Dogan Uncu
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
De Novo ◽  
Metastatic Breast ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Prognostic Features ◽  
Her 2

Abstract   BACKGROUND: There are different data in the literature about the consequences of the development of metastasis as de novo or recurrent. In this study, we retrospectively investigated the clinicopathologic and prognostic characteristics of HER-2 positive de novo and recurrent metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: The data of patients admitted to our clinic between 1996-2017 were analyzed retrospectively. The baseline features, treatments and survival data were recorded. Recurrent metastatic patients were further categorized as disease free interval (DFI) <24 months and DFI >24 months. The features of two groups were analyzed by pearson chi-square test. Survival were calculated by using the Kaplan-Meier method with the Long-rank test. p <0.05 was considered statistically significant. RESULTS: A total of 44 patients were included to study in which 20 patients in de novo HER-2 positive MBC group and 24 patients in recurrent HER-2 MBC group. There was no difference in baseline features between groups. The median OS in de novo and recurrent MBC group was 60.3 months and 43.9 months respectively (HR: 0.87, 95% CI 0.37-2.05, p=0.76). OS was not different between de novo MBC group and patients with DFI <24 months and with DFI > 24 months (p=0.135). CONCLUSION: Our study showed that baseline features of patients with de novo HER-2 positive MBC and recurrent HER-2 positive MBC did not differ from each other. The presence of metastasis at the time of diagnosis or during follow-up did not change response to treatments.  

Safety of a novel capecitabine dosing schedule when combined with lapatinib in patients with HER2-positive metastatic breast cancer refractory to trastuzumab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1131-1131
Author(s):  
T. A. Traina ◽  
M. Theodoulou ◽  
K. Feigin ◽  
S. Patil ◽  
S. Geneus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Optimal Schedule ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Ecog Performance Status ◽  
Study Results ◽  
Her 2 ◽  
Ecog Ps

1131 Background: Capecitabine (C) is active in breast cancer and is usually dosed for 14 days (d) followed by a 7d rest (14 - 7). We described a mathematical method which predicts the optimal schedule for C to be 7d followed by a 7d rest (7 - 7) (Norton et al, Amer Assn Can Res. 2005). The MTD of C(7 - 7) is 2,000mg BID (Traina et al, J Clin Oncol. April 2008). Lapatinib (L) improves time to progression when added to C(14 - 7) in patients (pts) with HER-2-positive (+) metastatic breast cancer (MBC) that progressed after trastuzumab (T). To optimize this effective combination, we are testing C(7 - 7) + L in a phase II trial. Methods: Eligible pts have measurable, HER-2(+) MBC that has progressed after T. HER-2(+)=IHC 3+ or FISH>2. Pts have normal LVEF by MUGA, ECOG performance status (PS) <2 and normal organ function. <3 prior chemotherapy (CRx) regimens are permitted. Prior fluoropyrimidine is excluded. Therapy (tx) consists of C (2,000 mg BID, 7 - 7) and L (1,250 mg, daily). Cycle length = 4 wk. Pts are evaluated for toxicity q4 weeks (wk), for response q12wk; LVEF by MUGA q12wk. Primary endpoint: response rate (RR). Secondary endpoints: toxicity, stable disease >6 months, PFS. Using a Simon optimal 2-stage design, with alpha = 10%, power = 90% to discriminate between RR 10% and 25%, 21 pts will be accrued to the first stage. If >2 pts respond, 29 additional pts will be enrolled. If >7/ 40 pts respond, then C(7 - 7) + L will be considered worthy of further study. Results: As of January 5, 2008, 6 pts are enrolled and evaluable. Median (med) age 64 yrs (42–71), med ECOG PS 1 (0–1), ER/PR(+) 3, HER-2(+) 6, sites of MBC: bone (2), viscera (4), soft tissue (5). Med baseline LVEF 62% (51–68%). Prior tx: Adjuvant: CRx (5), hormone tx (3), T (3); MBC: CRx (2), hormone tx (1), T (3). After a med of 3 cycles (1–4), there were no grade 3, 4, or 5 events. Tx-related toxicity is: Gr 2 fatigue (1); Gr 1 AST (4), diarrhea (3), ALT (2), vomiting (1), hand-foot (1), fatigue (1). No withdrawls due to reduced LVEF. Two pts evaluable for response: PR = 1, SD<6 mo = 1. Conclusions: Capecitabine (7 - 7) + lapatinib appears well tolerated compared to C(14 - 7)+L (Geyer et al). Additional safety and efficacy data is anticipated prior to this meeting. [Table: see text]

Serum EGFR and serum HER-2/neu are useful predictive and prognostic markers in metastatic breast cancer patients treated with metronomic chemotherapy

Cancer ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 509-517 ◽  
Author(s):  
Maria Teresa Sandri ◽  
Harriet Ann Johansson ◽  
Laura Zorzino ◽  
Michela Salvatici ◽  
Rita Passerini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Markers ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Breast Cancer Patients ◽  
Her 2

scholarly journals The Efficacy of Pyrotinib as a Third- or Higher-Line Treatment in HER2-Positive Metastatic Breast Cancer Patients Exposed to Lapatinib Compared to Lapatinib-Naive Patients: A Real-World Study

2021 ◽  
Vol 12 ◽  
Author(s):  
D. J Ouyang ◽  
Q. T Chen ◽  
M. Anwar ◽  
N. Xie ◽  
Q. C. Ouyang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Original Cohort

Background: Pyrotinib is a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor. Evidence of the efficacy of pyrotinib-based treatments for HER2-positive metastatic breast cancer (MBC) in patients exposed to lapatinib is limited.Methods: Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC were included in this retrospective study. The primary and secondary endpoints were overall survival (OS) and progression‐free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were implemented to balance important patient characteristics between groups.Results: Thirty (31.9%) patients were pretreated with lapatinib and subsequently received pyrotinib as an anti-HER2 treatment, and 64 (68.1%) patients did not receive this treatment. The OS and PFS indicated a beneficial trend in lapatinib-naive group compared to lapatinib-treated group in either the original cohort (PFS: 9.02 vs 6.36 months, p = 0.05; OS: 20.73 vs 14.35 months, p = 0.08) or the PSM (PFS: 9.02 vs 6.08 months, p = 0.07; OS: 19.07 vs 18.00 months, p = 0.61) or IPTW (PFS: 9.90 vs 6.17 months, p = 0.05; OS: 19.53 vs 15.10 months, p = 0.08) cohorts. Subgroup analyses demonstrated lapatinib treatment-related differences in PFS in the premenopausal subgroup and the no prior trastuzumab treatment subgroup, but no significant differences were observed in OS.Conclusion: Pyrotinib-based therapy demonstrated promising effects in HER2-positive MBC patients in a real-world study, especially in lapatinib-naive patients, and also some activity in lapatinib-treated patients.

Pyrotinib plus capecitabine for HER2-positive metastatic breast cancer patients with brain metastases (PERMEATE): A multicenter, single-arm phase II study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1037-1037
Author(s):  
Min Yan ◽  
Quchang Ouyang ◽  
Tao Sun ◽  
Limin Niu ◽  
Jin Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Her2 Positive

1037 Background: HER2-positive metastatic breast cancer (BC) has a high risk of brain metastases (BM), leading to poor survival. Small molecule tyrosine kinase inhibitor (TKI) with enhanced penetrability to the blood brain barrier combined with capecitabine have demonstrated promising clinical outcomes in HER2-positive metastatic BC patients with untreated (such as lapatinib) or previously treated (such as neratinib) BM. The randomized phase III PHOEBE trial has proved better efficacy of pyrotinib, an irreversible pan-HER receptor TKI, versus lapatinib when in combination with capecitabine in HER2-positive local relapsed or metastatic BC. This study was conducted to investigate the efficacy and safety of pyrotinib plus capecitabine in HER2-positive metastatic BC patients with BM. Methods: In this multicenter phase II trial (NCT03691051), eligible patients received pyrotinib 400 mg orally once daily without breaks and capecitabine 1000 mg/m2 orally twice daily for 14 days followed by 7 days off. Treatment was continued until disease progression or intolerable toxicity. Prior HER2 TKIs were not allowed. Cohort A included patients with radiotherapy-naive BM, and cohort B included those with progressive BM after whole brain radiotherapy or stereotactic conformal radiotherapy. The primary endpoint was confirmed central nervous system (CNS) objective response rate (ORR), as assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. Results: Between January 2018 and July 2020, a total of 78 female patients were included (Table). For cohort A (n = 59), the CNS ORR was 74.6% (95%CI: 61.6%-85.0%). For cohort B (n = 19), the CNS ORR was 42.1% (95%CI: 20.3%-66.5%). By the cutoff date on 25 January 2021, the median progression-free survival was 12.1 months (95%CI: 9.0-14.7) in cohort A and 5.6 months (95%CI: 3.4-10.7) in cohort B. The most common grade ≥3 adverse events were diarrhea (23.1% [18/78]), neutrophil count decreased (12.8% [10/78]), white blood cell count decreased (12.8% [10/78]), anemia (9.0% [7/78]), hand-foot syndrome (7.7% [6/78]), hypertriglyceridemia (6.4% [5/78]), and hypokalemia (5.1% [4/78]). Conclusions: Pyrotinib plus capecitabine resulted as an effective and safe treatment for HER2-positive BC patients with radiotherapy-naive BM, but the efficacy was modest in those with radiotherapy-treated BM. Clinical trial information: NCT03691051 .[Table: see text]

Sign in / Sign up

Export Citation Format

Share Document