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Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer.

ABSTRACT: The purpose of this investigation was to evaluate the efficacy of cisplatin chemotherapy in BRCA1 mutation carriers with metastatic breast cancer.In a phase II, open-label study, 20 patients with metastatic breast cancer who carried a mutation in BRCA1 were treated with cisplatin 75 mg/m2 intravenously every 3 weeks as part of a 21-day cycle for 6 cycles. Restaging studies to assess response were performed after cycles 2 and 6, and every three months thereafter.Between July 2007 and January 2009, 20 patients were enrolled. Baseline characteristics were as follows: 65% had prior adjuvant chemotherapy, 55% had prior chemotherapy for metastatic breast cancer; mean age was 48 years (ranges 32 to 70); 30% estrogen receptor (ER) or progesterone receptor (PR)+, 70% ER/PR/Human Epidermal Growth Factor Receptor 2 (HER2)- and 0% HER2+. Overall response rate was 80%; nine patients experienced a complete clinical response (45%) and seven experienced a partial response (35%). Overall survival was 80% at one year, 60% at two years and 25% at three years. Four of the 20 patients are alive four years after initiating treatment. The median time to progression was 12 months. The median survival from the start of cisplatinum treatment was 30 months. Cisplatin-related adverse events, including nausea (50%), anemia (5%) and neutropenia (35%) were mostly mild to moderate in severity.This phase II study demonstrates that cisplatin chemotherapy has high activity in women with a BRCA1 mutation and metastatic breast cancer and is generally well tolerated.This trial is registered retrospectively on the clinical trials website ClinicalTrials.gov. The identifier is NCT01611727.

SUBMITTER: Byrski T

PROVIDER: S-EPMC3680929 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer.

Byrski Tomasz T Dent Rebecca R Blecharz Pawel P Foszczynska-Kloda Malgorzata M Gronwald Jacek J Huzarski Tomasz T Cybulski Cezary C Marczyk Elzbieta E Chrzan Robert R Eisen Andrea A Lubinski Jan J Narod Steven A SA

Breast cancer research : BCR 20120720 4

<h4>Introduction</h4>The purpose of this investigation was to evaluate the efficacy of cisplatin chemotherapy in BRCA1 mutation carriers with metastatic breast cancer.<h4>Methods</h4>In a phase II, open-label study, 20 patients with metastatic breast cancer who carried a mutation in BRCA1 were treated with cisplatin 75 mg/m2 intravenously every 3 weeks as part of a 21-day cycle for 6 cycles. Restaging studies to assess response were performed after cycles 2 and 6, and every three months thereaft ...[more]

PMID: 22817698

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Project description:BackgroundThere is no standard therapy for metastatic biliary tract carcinoma (BTC) refractory to first-line chemotherapy. Apatinib, a VEGFR2 tyrosine kynase inhibitor, showed an activity against BTC xenografts in preclinical models. We conducted an exploratory study to evaluate the efficacy and safety of apatinib in patients with metastatic BTC.MethodsThis is a single-arm phase II study [ClinicalTrials.gov identifier: NCT03427242]. Eligible patients were aged 18 years or older; histologically confirmed metastatic BTC; refractory or intolerance to at least one chemotherapeutic regimen; no prior use of anti-angiogenic targeted drugs; Eastern Cooperative Oncology Group performance status of 0-2. Patients received oral apatinib 500 mg each day continuously until unacceptable toxicity or tumor progression. The primary endpoint was progress free survival (PFS). The secondary endpoint was overall survival (OS), objective response rate (ORR) and treatment safety.ResultsA total of 22 patients were recruited. All of them received apatinib medication. The median age was 63 (44-75) years old. Twenty patients received efficacy evaluation after treatment. The objective response rate (ORR) and disease control rate (DCR) were 15.0% and 60.0%, respectively. The median PFS was 2.73 months [95% confidence interval (CI): 1.74-3.72 months], with 6 months PFS rate of 27.3% (95% CI: 8.7-45.9%). The median OS was 4.81 months (95% CI: 3.16-10.9 months), with 12 months OS rate of 36.4% (95% CI: 16.2-56.6%). Nine out of 22 patients (40.9%) had grade 3/4 adverse events. The most common grade 3/4 adverse events were hand-foot skin syndrome [three (13.6%) patients] and hypertension [two (9.1%) patients]. No treatment-related death occurred.ConclusionsFor patients with metastatic BTC, apatinib showed an anti-tumor activity with acceptable safety, which deserves the further clinical trial.This trial was prospectively registered on ClinicalTrials.gov [NCT03427242]. Date of first patient enrollment: 26 January 2018. Date of registration (date of first posted): 9 February 2018.

Project description:BackgroundMerkel cell carcinoma is a rare, aggressive skin cancer with poor prognosis in patients with advanced disease. Current standard care uses various cytotoxic chemotherapy regimens, but responses are seldom durable. Tumour oncogenesis is linked to Merkel cell polyomavirus integration and ultraviolet-radiation-induced mutations, providing rationale for treatment with immunotherapy antibodies that target the PD-L1/PD-1 pathway. We assessed treatment with avelumab, an anti-PD-L1 monoclonal antibody, in patients with stage IV Merkel cell carcinoma that had progressed after cytotoxic chemotherapy.MethodsIn this multicentre, international, prospective, single-group, open-label, phase 2 trial, patients with stage IV chemotherapy-refractory, histologically confirmed Merkel cell carcinoma (aged ≥18 years) were enrolled from 35 cancer treatment centres and academic hospitals in North America, Europe, Australia, and Asia. Key eligibility criteria were an ECOG performance status of 0 or 1, measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, adequate haematological, hepatic, and renal function, and immune-competent status (patients with HIV, immunosuppression, haematological malignancies, and previous organ transplantation were excluded). Patient selection was not based on PD-L1 expression or Merkel cell polyomavirus status. Collection of biopsy material or use of archival tissue for these assessments was mandatory. Avelumab was given intravenously at a dose of 10 mg/kg every 2 weeks. The primary endpoint was confirmed objective response (complete response or partial response) assessed according to RECIST version 1.1 by an independent review committee. Safety and clinical activity were assessed in all patients who received at least one dose of study drug (the modified intention-to-treat population). This trial is registered with ClinicalTrials.gov as NCT02155647.FindingsBetween July 25, 2014, and Sept 3, 2015, 88 patients were enrolled and received at least one dose of avelumab. Patients were followed up for a median of 10·4 months (IQR 8·6-13·1). The proportion of patients who achieved an objective response was 28 (31·8% [95·9% CI 21·9-43·1]) of 88 patients, including eight complete responses and 20 partial responses. Responses were ongoing in 23 (82%) of 28 patients at the time of analysis. Five grade 3 treatment-related adverse events occurred in four (5%) patients: lymphopenia in two patients, blood creatine phosphokinase increase in one patient, aminotransferase increase in one patient, and blood cholesterol increase in one patient; there were no treatment-related grade 4 adverse events or treatment-related deaths. Serious treatment-related adverse events were reported in five patients (6%): enterocolitis, infusion-related reaction, aminotransferases increased, chondrocalcinosis, synovitis, and interstitial nephritis (n=1 each).InterpretationAvelumab was associated with durable responses, most of which are still ongoing, and was well tolerated; hence, avelumab represents a new therapeutic option for advanced Merkel cell carcinoma.FundingMerck KGaA, Darmstadt, Germany.

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Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer.

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Results of a phase II open-label, non-randomized trial of cisplatin chemotherapy in patients with BRCA1-positive metastatic breast cancer.

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