Apatinib plus vinorelbine versus vinorelbine for advanced triple-negative breast cancer with failed first or second-line treatment: The NAN trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1075-1075
Author(s):  
Doudou Li ◽  
Zhonghua Tao ◽  
Biyun Wang ◽  
Leiping Wang ◽  
Jun Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Disease Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Line Treatment ◽  
Second Line ◽  
Grade 3 ◽  
To Receive

1075 Background: No standard treatment exists for triple negative breast cancer (TNBC) with failure of multi-line therapies. Apatinib is a small-molecule tyrosine kinase inhibitor that has promising anti-angiogenesis and antitumor activity for TNBC. We aimed to evaluate the safety and efficacy of adding apatinib to chemotherapy in patients with metastatic TNBC with failed first/second-line treatment. Methods: This randomized, open-label, phase 2 trial recruited patients with advanced TNBC who failed to receive first or second-line treatment. A total of 66 patients were randomly assigned, in a 1:1 ratio, to receive vinorelbine 25 mg/m2 (days 1, 8, 15) or vinorelbine 20 mg/m2 (days 7, 14, 21) with apatinib (250 mg once daily, days 1-5, 8-12, 15-19, if tolerable, the second cycle started with 500 mg per day) in 28-day cycles. The efficacy was evaluated every two treatment cycles (8 weeks ± 3 days). According to the RECIST criterion, patients with CR, PR and SD continued treatment until disease progression or unacceptable toxicity or withdrawal of consent. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), overall response rate (ORR) and safety. Results: Between Sep 14, 2017 and Dec 08, 2020, 66 patients underwent randomization. Median follow-up was 21.3 months. 33 received apatinib plus vinorelbine and 32 received vinorelbine (1 was withdrawal of consent). Median PFS was significantly longer in the apatinib plus vinorelbine group than in the vinorelbine group (3.8 months vs. 1.9 months; hazard ratio for disease progression or death, 1.76; 95% confidence interval [CI], 1.02 to 3.05; P= 0.039). Median OS was 14.6 months with apatinib plus vinorelbine and 14.1 months with vinorelbine (HR,1.34; 95% CI, 0.60 to 3.00; P= 0.469). The ORR was 48.5% in the apatinib plus vinorelbine group and 31.3% in the vinorelbine group ( P= 0.156). The most common treatment-related hematologic grade 3–4 adverse events in those treated with apatinib plus vinorelbine versus vinorelbine, respectively, were leukopenia (42.4% vs. 34.4%), granulocytopenia (57.6% vs. 28.1%), anemia (9.1% vs. 12.5%) and thrombocytopenia (3.1% vs. 3.0%). The most frequent grade 3 nonhematologic toxicities were hand–foot syndrome (21%), proteinuria (9%), hypertension (9%) and increased ALT (9%) and which only occurred in apatinib plus vinorelbine group. No treatment-related nonhematologic grade 4 adverse events or treatment-related deaths were observed. Conclusions: Collectively, among patients with advanced TNBC with failed first/second-line treatment, apatinib plus vinorelbine show a promising benefit in PFS compared to vinorelbine monotherapy. Apatinib plus vinorelbine regimen shows promising efficacy and manageable toxicity, which might be a previously unappreciated therapeutic option for advanced TNBC. Clinical trial information: NCT03254654 .

A phase Ib study of TQB2450 plus anlotinib in patients with advanced triple-negative breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1074-1074
Author(s):  
Jiayu Wang ◽  
Binghe Xu ◽  
Tao Sun ◽  
Quchang Ouyang ◽  
Yiqun Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Dose Escalation ◽  
Triple Negative ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Expansion Phase ◽  
Qt Interval Prolongation ◽  
Grade 3

1074 Background: TQB2450 is a humanized monoclonal antibody targeting programmed death-ligand 1 (PD-L1). Anlotinib is an antiangiogenic small molecule, multi-target tyrosine kinase inhibitor that has improved clinical outcomes in various solid tumors. This phase 1b study aims to evaluate the safety and efficacy of TQB2450 plus anlotinib for patients with advanced triple-negative breast cancer (TNBC) after the failure of standard therapy. Methods: This ongoing study included a dose-escalation phase and an expansion phase. Advanced TNBC patients with prior anthracyclines and/or taxanes treatment and failed at least first-line therapy were enrolled. In the dose-escalation phase, eligible patients received anlotinib (8mg, 10mg, and 12mg, qd, days 1-14; 21 days per cycle) plus TQB2450 (1200mg, day 1; 21 days per cycle) following the conventional 3+3 design. If the starting dose of 10mg anlotinib led to ≥2 dose-limiting toxicities (DLTs), 8mg anlotinib would be administered. After the dose-escalating phase, eligible patients were enrolled into the expansion cohort. The primary endpoint was objective response rate (ORR), and the secondary endpoints were overall survival (OS), disease control rate (DCR), progression-free survival (PFS), and safety. Results: Between May 29, 2019, and December 31, 2020, in the dose-escalation phase, three patients receiving 10mg anlotinib plus 1200mg TQB2450 had no DLTs in the first cycle, neither did three patients with 12mg anlotinib plus TQB2450. Next, 28 patients with advanced TNBC received 12 mg anlotinib plus TQB2450 in the expansion phase. Finally, a total of 34 patients were included with median age of 49.5 (32-70) and median prior lines of 2 (1-6). Numbers of patients with prior platinum therapy: 16, prior anthracycline therapy: 32. The ORR was 26.47% (9/34) and DCR was 82.35% (28/34). The median PFS was 8.57 months. Seventeen patients experienced grade 3 treatment-related AEs (TRAEs). Most frequently occurring (>5%) grade 3 TRAEs were QT interval prolongation (17.65%), hypertension (14.71%), diarrhea (8.82%), hand-foot syndrome (HFS) (8.82%), and hypertriglyceridemia (5.88%). Conclusions: TQB2450 plus anlotinib showed an acceptable safety profile with promising activity for previously anthracyclines and/or taxanes-treated advanced TNBC patients. Clinical trial information: NCT03855358 .[Table: see text]

Phase II study of eribulin in combination with gemcitabine for the treatment of patients with locally advanced or metastatic triple negative breast cancer: ERIGE trial on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1095-1095
Author(s):  
Antonino Musolino ◽  
Rosa Porzio ◽  
Daniela Rubino ◽  
Antonio Frassoldati ◽  
Alessia Caldara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Objective Response ◽  
Locally Advanced ◽  
Combination Regimen ◽  
Line Treatment ◽  
Second Line ◽  
Tumor Cell Death ◽  
Study Population

1095 Background: There are no well-established chemotherapy regimens for metastatic triple negative breast cancer. The combination of a microtubule inhibitor (eribulin) with a nucleoside analog (gemcitabine) may synergistically induce tumor cell death, especially in tumors like triple negative breast cancers (TNBC) characterized by high cell proliferation, aggressive tumor behavior, and chemo-resistance. Methods: We performed an open-label, national multicenter phase 2 study evaluating the combination of eribulin (0.88 mg/m2) plus gemcitabine (1000 mg/m2) on day 1 and 8, q21 as either first- or second-line treatment of locally advanced or metastatic TNBC. The Simon's optimal two-stage design was used for estimating objective response rate (ORR) as study primary endpoint. A prospective, molecular correlative study was carried out on germinal DNA of study population to assess the role of germinal DNA polymorphisms and BRCA mutations in predicting efficacy and toxicity of the combination regimen. Results: From July 2013 to September 2016 , 83 (37 in the first stage, 46 in the second one) assessable patients were enrolled. Median age at baseline was 56 years. Sixty-six and 17 patients were in first or second-line treatment, respectively. All patients were previously treated with an anthracycline and/or a taxane. With regard to the first stage of study enrolment, patients received a median number of 6 cycles of treatment. The ORR (CR+PR) was 43.24% (90% CI 29.3-58.0) and the clinical benefit rate (CR+PR+SD) was 64.9% (90% CI: 50.1%-77.8%). The most common grade 3/4 AEs ( > 10% of patients) were neutropenia without febrile neutropenia and liver toxicity. Grade 1/2 AEs were fatigue, anemia, thrombocytopenia, diarrhea, alopecia, peripheral neuropathy, and oral mucositis. Conclusions: The combination of eribulin and gemcitabine shows promising activity and a moderate toxicity profile in metastatic TNBC. More mature toxicity and outcome data of the final study population and correlation with genome analysis will be presented at the meeting. Clinical trial information: 2012-003505-10.

scholarly journals Inclusion of Platinum Agents in Neoadjuvant Chemotherapy Regimens for Triple-Negative Breast Cancer Patients: Development of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Medical Oncology (AIOM)

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1137 ◽  
Author(s):  
Maria Vittoria Dieci ◽  
Lucia Del Mastro ◽  
Michela Cinquini ◽  
Filippo Montemurro ◽  
Laura Biganzoli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Febrile Neutropenia ◽  
Adverse Events ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Medical Oncology ◽  
Serious Adverse Events ◽  
Assessment Development ◽  
Grade 3

In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated the inclusion of platinum in neoadjuvant chemotherapy regimens for TNBC, leading to non-univocal results. The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on Breast Cancer developed a clinical recommendation on the addition of platinum to anthracycline/taxane-based neoadjuvant chemotherapy for TNBC by using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology and the Evidence to Decision framework (EtD). Five studies were eligible. The panel identified the following outcomes of benefit: pCR (critical), disease/event-free survival (DFS/EFS, critical), and overall survival (OS, critical). The panel identified febrile neutropenia (critical), serious adverse events (critical), anemia grade 3–4 (important), thrombocytopenia grade 3–4 (important) as outcomes of harms. The probability of pCR was higher in the platinum-based chemotherapy group versus control group (RR = 1.45, 95%CI 1.28–1.64); however, no impact on long-term outcome was observed. Neoadjuvant treatment regimens containing platinum resulted in a non-significant increase in the risk of febrile neutropenia and in a significant increase in the risk serious adverse events, G3–G4 anemia and G3–G4 thrombocytopenia: 11.3% versus 0.8%, RR = 15.66 (95%CI 6.38–38.44). The panel judged uncertain/favorable the benefit/harms balance. The panel’s final recommendation was conditional in favor of the inclusion of platinum in anthracycline/taxane-based neoadjuvant regimens for TNBC.

Phase II study of neoadjuvant chemotherapy with a metronomic regimen of paclitaxel + cyclophosphamide + capecitabine followed by 5-fluorouracil + epirubicin + cyclophosphamide in operable triple-negative breast cancer (JBCRG-13 study).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1048-1048
Author(s):  
Kenji Higaki ◽  
Norikazu Masuda ◽  
Toshimi Takano ◽  
Nobuki Matsunami ◽  
Takashi Morimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Conservation ◽  
Dose Intensity ◽  
Complete Response ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Clinical Trial Information

1048^ Background: Triple-negative breast cancer (TNBC) is generally associated with a poor prognosis. Combination therapy with anthracyclines and taxanes is widely used as preoperative systemic chemotherapy (PST), but pathological complete response (pCR) rate is ≤50%. We conducted metronomic PST in TNBC patients. Methods: Patients had primary breast cancer (T1C-3N0M0 or T1-3N1M0) with low ER expression (<10%) diagnosed with either a triple-negative or HER2-negative invasive tumor. They received 4 cycles of a metronomic PCX regimen followed by 4 cycles of 5-fluorouracil (500 mg/m2, q3w) + epirubicin (100 mg/m2, q3w) + cyclophosphamide (500 mg/m2, q3w) (FEC regimen). The metronomic PCX regimen includes weekly administration of paclitaxel (80 mg/m2; days 1, 8, 15), cyclophosphamide (50 mg/body; po, days 1-21) and capecitabine (1200 mg/m2; po, daily), with one cycle set to 21 days. Primary endpoint was pCR rate. Results: Between March 2010 and September 2011, 41 patients were enrolled and 40 patients were treated. Characteristics of these 40 pts (ITT population) were: median age 52 years (range, 33-69), median tumor size 23.7 mm (range, 3.5-82), N(+) in 16 pts (40%), and estrogen receptor weakly positive (ER;1-9%) in 7 pts (17.5%). Median dose intensity for paclitaxel, cyclophosphamide and capecitabine was 89.7%, 92.1% and 89.8%, respectively. Five pts requested discontinuation of PST during PCX and 2 during FEC, primarily due to adverse events, leaving a per protocol population of 33 pts. pCR (ypT0/Tis ypN0) rate was 54.5% (18/33). 22 pts achieved CR, and ORR was 93.9% (95% CI, 79.8-99.3) as assessed by MRI or CT. Breast conservation rate was 72.7% (24/33), and 5 of 13 pts changed to partial resection from pre-planned total mastectomy. Grade 3-4 adverse events were neutropenia (35%), febrile neutropenia (25%), leucopenia (25%), and hand-foot syndrome (7.5%). There was no SAE report, and most pts completed treatment as outpatients. Conclusions: Metronomic PCX followed by FEC provided a high pCR rate and was manageable as PST in patients with TNBC. Clinical trial information: UMIN000003570.

scholarly journals How I treat metastatic triple-negative breast cancer

ESMO Open ◽  
2019 ◽  
Vol 4 (Suppl 2) ◽  
pp. e000504 ◽  
Author(s):  
Rafael Caparica ◽  
Matteo Lambertini ◽  
Evandro de Azambuja
Keyword(s):  
Breast Cancer ◽  
Disease Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Single Agent ◽  
Treatment Algorithm ◽  
Predictive Biomarkers ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Triple-negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a bad prognosis. More than one-third of patients with TNBC will present distant metastases during the course of their disease. Although chemotherapy has been the main treatment option for metastatic TNBC for a long time, this scenario has changed recently with the advent of the polyadenosine diphosphate-ribose polymerase inhibitors (PARPis) for patients harbouring a mutation in the BRCA genes (BRCAmut) and also with the results of immunotherapy in patients with PD-L1-positive tumours. The present manuscript proposes a treatment algorithm for patients with metastatic TNBC based on the currently available, most relevant literature on the topic. For patients with a BRCAmut and able to tolerate chemotherapy, we recommend initiating treatment with platins (carboplatin/cisplatin) and to start PARPis at disease progression. For patients with PD-L1-positive tumours (PD-L1 expression on tumour-infiltrating immune cells ≥1%), we recommend first-line treatment with nab-paclitaxel and atezolizumab, when available. In patients without a BRCA mutation and with PD-L1-negative tumours, we recommend single-agent chemotherapy with taxanes (paclitaxel or docetaxel) as a first-line treatment. In patients with a high disease burden or who are very symptomatic, combinations such as anthracyclines plus cyclophosphamide or platins with taxanes are valid options. Chemotherapy should be maintained until the occurrence of disease progression or limiting toxicities. After progression to first-line chemotherapy, anthracyclines are an option for patients who received taxanes and vice versa. For patients who progressed to taxanes and anthracyclines, or who present contraindications to these agents, fluorouracil/capecitabine, eribulin, gemcitabine, cisplatin/carboplatin, vinorelbine and ixabepilone are alternatives. The treatment of TNBC is constantly evolving, and the inclusion of patients in ongoing trials evaluating new targeted agents, immunotherapy and predictive biomarkers should be encouraged, in an attempt to improve metastatic TNBC treatment outcomes.

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