New biweekly combination of trastuzumab, docetaxel, and gemcitabine for HER2-positive metastatic breast cancer: First early results from a phase II multicentric trial on behalf of Gruppo Oncologico Italia Meridionale

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1096-1096
Author(s):  
S. Cinieri ◽  
L. Orlando ◽  
V. Lorusso ◽  
G. Filippelli ◽  
E. Maiello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Metastatic Breast ◽  
Clinical Activity ◽  
Breast Cancer Patients ◽  
Who Grade ◽  
End Point ◽  
Early Results ◽  
Her 2

1096 Background: The clinical activity of the combination of chemotherapy plus trastuzumab in HER-2 overexpressing metastatic breast cancer has been well documentated. We report the first results in terms of efficacy and safety of a phase II trial on biweekly combination of trastuzumab plus docetaxel and gemcitabine as first line therapy in HER-2-positive metastatic breast cancer patients. Methods: Patients at first relapse or with synchronous metastasis, were treated with trastuzumab (4 mg/kg, loading dose 6 mg/kg) plus gemcitabine (1000 mg/m2) plus docetaxel (50 mg/m2) as biweekly schedule. Primary end-point was overall response rate (ORR), secondary end-point time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks), and tolerability. Based on previous data, an ORR greater than 60% was considered to indicate clinical activity in this two stage design trial. Results: A total of 26 patients with histologically confirmed, measurable MBC, tumors scored as +3 positive for HER-2 by immuno-histochemistry or FISH +, no pretreated with chemotherapy or trastuzumab for metastatic disease have been enrolled, 22 actually evaluable for response and toxicity. Median age was 49 years (range 34–66), visceral metastases were present in most patients (73%). Median number of cycles was 8 (range 3–12). The ORR was 86% (95% CI, 80–91%), with two CR (9 %) and 17 PR (77%). 3 patients had SD, 1 prolonged (14%). The CBR was 91% (95% CI, 87%-94%). No progression of disease was observed. Median TTP was 7 months (range 5- 9+ months). The worst toxicity was WHO grade 2 neutropenia and grade 2 gastric pain. Conclusions: In this phase II study, the biweekly combination of trastuzumab, gemcitabine, and docetaxel in HER-2-positive breast cancer is very active. The toxicity observed was manageable and did not lead to treatment discontinuation. Thus, the patients accrual is ongoing to the preset target of 50 patients. No significant financial relationships to disclose.

Clinical activity of chronic oral etoposide in previously treated metastatic breast cancer.

1994 ◽  
Vol 12 (5) ◽  
pp. 986-991 ◽  
Author(s):  
M Martín ◽  
A Lluch ◽  
A Casado ◽  
P Santabárbara ◽  
E Adrover ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Soft Tissues ◽  
Metastatic Breast ◽  
World Health ◽  
Clinical Activity ◽  
Oral Etoposide ◽  
Breast Cancer Patients ◽  
Who Grade ◽  
Intention To Treat

PURPOSE This study was undertaken to assess the antitumor activity and tolerance of chronic oral etoposide (50 mg/m2/d for 21 days every 4 weeks) in metastatic breast cancer (MBC). PATIENTS AND METHODS Forty-three consecutive metastatic breast cancer patients with at least one site of measurable disease entered the study. All patients had received prior chemotherapy (adjuvant, three patients; adjuvant plus chemotherapy for metastases, 21; chemotherapy for metastases, 19). Twenty-two and 21 patients had also received prior hormonal and radiation therapy, respectively. RESULTS Thirty-five percent of patients (15 of 43; 95% confidence interval, 21% to 51%) had objective responses, according to an intention-to-treat analysis. Responses were seen in lymph nodes (six of 14), skin and soft tissues (eight of 16), lung (six of 14), lytic lesions of the bone (two of six), liver (four of 23), and peritoneum (one of one). The median duration of response was 7 months (range, 3+ to 12). The main toxic side effects were leukopenia (overall, 65% of patients; World Health Organization [WHO] grade 4, 21%), thrombocytopenia (21%; WHO grade 4, 5%) and anemia (51%; WHO grade 4, 5%). Nine patients (21%) required a 25% dose reduction because of myelosuppression, and one patient abandoned treatment because of gastrointestinal toxicity and severe asthenia. Ninety-one percent of patients developed alopecia, 39.5% had mucositis (WHO grade 3, 9.5%) and 60.5% had some degree of emesis (11.5% nausea, 46.5% transient vomiting, 2.5% intractable vomiting). No toxic deaths occurred. CONCLUSION Chronic oral etoposide appears to be an active and well-tolerated regimen in MBC patients previously exposed to chemotherapy. This schedule of etoposide administration warrants further studies, alone or in combination, in MBC.

Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

scholarly journals Effect and Safety of Anti-PD-1/PD-L1 Monotherapy for Metastatic Breast Cancer: A meta-analysis

2019 ◽  
Author(s):  
Yihang Qi ◽  
Xiangyi Kong ◽  
Xiangyu Wang ◽  
Jie Zhai ◽  
Yi Fang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Rate ◽  
Response Rate ◽  
Meta Analysis ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Clinical Activity ◽  
Breast Cancer Patients ◽  
Severe Grade

Abstract Background. Given that no approved targeted agents for metastatic triple-negative breast cancer (mTNBC) and no opportunity of surgery for metastatic breast cancer (MBC), new treatment options are urgently to be discovered. The anti-PD-1/PD-L1 immunotherapy may be effective, and what we should be aware of is the response rate and adverse events. Methods. The PUBMED, EMBASE, Cochrane and www.clinicaltrials.gov databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1; metastatic; breast cancer. R© package Meta was used to pool incidence. Results. Six studies including 586 advanced breast cancer patients treated with anti-PD-1/PD-L1 agents were included in this meta-analysis. The anti-PD-1/PD-L1 agents include pembrolizumab, atezolizumab and avelumab. Among these patients, CR was 1.26%, PR was 7.65%, ORR was 9.85% and DCR was 18.33%. We also found that the response rate was closely associated with the expression of PD-L1 biomarker (PD-L1+ vs PD-L1-): the CR was 2.71% vs 0.00%; the PR was 9.93% vs 2.69%; the ORR was 10.62% vs 3.07%; the DCR was 17.95% vs 4.71%. 1-year overall survival rate and 6-months progression-free survival rate were 43.34% and 17.24%. Respectively, the overall incidence of AEs was 64.18% in any grade and 12.94% in severe grade. The incidence of irAEs was 14.75%. Besides, the incidence of discontinue and death due to treatment-related AEs was about 3.06% and 0.31% respectively. When the detailed AEs were analyzed, most treatment-related AEs of any grade were arthraigia, asthenia, decreased appetite; most common treatment-related AEs of severe grade were anemia, autoimmune hepatitis, diarrhea; the most common irAEs were hypothyroidism , followed by hyperthyroidism, pneumonitis and infusion-related reaction. Conclusions. Anti-PD-1/PD-L1 monotherapy showed a manageable safety profile and had a durable anti-tumor clinical activity in a subset of patients with mTNBC or MBC. PD-L1 expression may be correlated to a higher probability of clinical response.

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