A phase II single-arm, multicenter, open-label neoadjuvant study of pembrolizumab in combination with nab-paclitaxel followed by pembrolizumab in combination with epirubicin and cyclophosphamide in patients with triple-negative breast cancer: Neoimmunoboost.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12647-e12647
Author(s):  
Peter A. Fasching ◽  
Andreas Hartkopf ◽  
Hans-Christian Kolberg ◽  
Lothar Haeberle ◽  
Sarah Wetzig ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Complete Response ◽  
Trial Participation ◽  
Clinical Response Rate ◽  
Open Label ◽  
Secondary Endpoints

e12647 Background: The NeoImmunoboost study (NCT03289819) was designed to evaluate the pathological complete response (pCR) rate and safety of a neoadjuvant combination of the PD-1 antibody pembrolizumab and nab-paclitaxel followed by pembrolizumab with epirubicin and cyclophosphamide in patients with early triple negative breast cancer (TNBC). Methods: This is a prospective, single-arm, multi-center, open-label phase II clinical trial. Female patients with early TNBC were eligible for trial participation. Patients received 12 cycles of weekly nab-paclitaxel intravenous (i.v.) 125 mg/m² body surface area (BSA) in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w; followed by 4 cycles of epirubicin i.v. 90 mg/m² BSA and cyclophosphamide i.v. 600 mg/m² BSA q3w in combination with 4 cycles of pembrolizumab i.v. 200 mg q3w. After 25 patients the protocol was amended, with an initiation boost of 1 cycle of pembrolizumab i.v. 200 mg q3w monotherapy prior to the chemotherapy. Primary trial endpoint was pCR. Secondary endpoints included safety and clinical response rate. Results: Between March 2018 and October 2019, 53 patients were included into the trial. Until now, 47 patients have completed trial treatment and 6 patients are still receiving therapy. 28 patients have received the initiation boost with pembrolizumab, 25 patients did not receive the initiation boost. Up to now, 4 patients terminated the therapy prematurely. Conclusions: pCR data of all patients will be available at the meeting and results of the pCR rates and selected secondary endpoints will be presented at the meeting. Clinical trial information: NCT03289819.

Phase II neoadjuvant trial with carboplatin and eribulin mesylate in patients with triple-negative breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS1134-TPS1134 ◽  
Author(s):  
Sara E. Barnato ◽  
Jacqueline Sara Jeruss ◽  
Kevin P. Bethke ◽  
Nora M. Hansen ◽  
Seema Ahsan Khan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Solid Tumors ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Clinical Response Rate ◽  
Clinical Activity ◽  
Eribulin Mesylate

TPS1134 Background: Several neoadjuvant trials have been conducted in triple negative breast cancer (TNBC) with platinum agents with pathologic complete response (pCR) ranging from 16%-32%. Eribulin mesylate, a nontaxane microtubule dynamics inhibitor, has clinical activity as monotherapy in breast cancer and other solid tumors. A recent phase I trial found the combination of eribulin mesylate with carboplatin was well tolerated and showed activity in advanced solid tumors. The recommended dose for future trials was eribulin mesylate 1.1 mg/m2 and carboplatin AUC6. We proposed a neoadjuvant phase II trial with the combination of carboplatin and eribulin in patients with TNBC. Methods: This is a non-randomized, open-label, multi-center, phase II clinical trial of eribulin and carboplatin enrolling histologically-confirmed TNBC patients. Our primary endpoint is to determine the pCR in TNBC patients treated with the combination of carboplatin and eribulin. Secondary endpoints include determination of the clinical response rate, toxicity evaluation and measurement of stem cell and TLE3 as a biomarker of response to eribulin therapy. To obtain an alpha of 0.10 and a power of 0.90, a sample size of 30 patients is required to detect a pCR rate >=30%. 10 of the planned 30 patients have been enrolled to date. Treatment will be given every 3 weeks for a total of 4 cycles of therapy. There will be an initial safety run-in to evaluate the appropriate dose of eribulin in this population. The first 10 patients will receive eribulin at 1.4 mg/m2 (intravenously over 2-5 minutes) followed by carboplatin AUC=6 (intravenously over 30 minutes). After the 10th patient has been enrolled, the study will be temporarily suspended pending review; toxicity will be assessed for these first 10 patients (cycle 1 only) to assess whether this dose of eribulin will be used for the remaining patients or if a reduction to a dose of 1.1 mg/m2 will be required. Definitive surgery will be performed 3-8 weeks after completion of therapy, which will conclude the duration of the study. Clinical Trial Registry Number NCT01372579.

scholarly journals A Prospective, Single-Arm, Phase II Trial of Apatinib Combined With Nab-Paclitaxel and Carboplatin for The Neoadjuvant Treatment of Triple-Negative Breast Cancer

2021 ◽  
Author(s):  
Tianyu Zeng ◽  
Jue Wang ◽  
Wei Li ◽  
Yiqi Yang ◽  
Fan Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Response Rate ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Axillary Lymph

Abstract Background: Pathological complete response (pCR) is essential for improvements of prognosis in triple-negative breast cancer (TNBC). We evaluated the efficacy of apatinib combined with nab-paclitaxel and carboplatin in patients in this phase II clinical trial.Methods: Women with hormone receptor- and human epidermal growth factor receptor 2 (HER2)- negative, stage II/III breast cancer received six cycles of 75 mg/m2 docetaxel, carboplatin (AUC = 5) and 15 mg/kg bevacizumab every 21 days. The primary end point was pathological complete response (pCR) in the primary breast and axillary lymph nodes (ALN).Results: Thirty-two patients were recruited into the clinical trial, the vast majority of the patients had stage III tumors (65.6%) and the median longest tumor size was 3.5 cm. The pCR rate was 43.8% (n = 14); clinical response rate 93.8% (n = 30); complete response rate 21.9% (n = 7); partial response rate 71.9% (n = 23); stable disease 6.2% (n = 2). After surgery, 7 (63.6%) of the 11 patients without axillary lymph node metastasis achieved a pCR. The median target lesions in breast reduced to 1.2 cm after the third cycle treatment and 0.9cm after the last cycle. Most frequent grade 3/4 adverse events were thrombopenia (40.6%, n = 13) and neutropenia (25%, n = 8). Conclusions: Neoadjuvant apatinib, combined with albumin paclitaxel and carboplatin resulted in an encouraging pCR rate in locally advanced breast cancer and no major safety concerns during the therapy.Clinical trial registration: NCT03650738

scholarly journals Open-label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer

JAMA Oncology ◽  
2019 ◽  
Vol 5 (8) ◽  
pp. 1132 ◽  
Author(s):  
Shaveta Vinayak ◽  
Sara M. Tolaney ◽  
Lee Schwartzberg ◽  
Monica Mita ◽  
Georgia McCann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Open Label

scholarly journals Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)

2015 ◽  
Vol 33 (1) ◽  
pp. 13-21 ◽  
Author(s):  
William M. Sikov ◽  
Donald A. Berry ◽  
Charles M. Perou ◽  
Baljit Singh ◽  
Constance T. Cirrincione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Stage Ii ◽  
Open Label ◽  
Grade 3 ◽  
Dose Dense ◽  
The Impact

Purpose One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent.

An adaptive randomized phase II trial to determine pathologic complete response with the addition of carboplatin with and without ABT-888 to standard chemotherapy in the neoadjuvant treatment of triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS1135-TPS1135
Author(s):  
Tiffany P. Avery ◽  
Adam C. Berger ◽  
Albert J. Kovatich ◽  
Hallgeir Rui ◽  
Terry Hyslop ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Parp Inhibitors ◽  
Weekly Cycles ◽  
Carboplatin Auc

TPS1135 Background: Inhibition of poly (ADP-ribose) polymerase (Parp) is a potential targeted therapy for triple-negative breast cancer (TNBC). Clinical trials of Parp inhibitors in metastatic TNBC have shown conflicting results. Issues regarding the use of Parp inhibitors in TNBC include choosing a selective Parp inhibitor and selecting an appropriate chemotherapy backbone. The current trial addresses these questions by combining a validated Parp inhbitor, ABT-888, with carboplatin and paclitaxel. Platinum agents have shown synergy with Parp inhibitors in preclinical models and efficacy in clinical trials. The combination of paclitaxel and carboplatin with Parp inhibitors has shown efficacy in phase I trials. Methods: This is a phase II, two-arm neoadjuvant trial of women with TNBC. Eighty patients will be enrolled. Randomization will follow a 1:1 allocation initially, then will follow a Bayesian adaptive allocation in which each prior response will be evaluated and patients assigned preferentially to the better responding arm. The primary endpoint is pathologic complete response (pCR). Secondary endpoints include correlation of pCR with biomarkers, imaging, and circulating tumor cells (CTCs). Treatment: Arm 1: Paclitaxel 80 mg/m2 + carboplatin AUC=2 (12 weekly cycles) + filgrastim followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 (4 cycles every 3 weeks) + pegfilgrastim. Arm 2: ABT-888 (150mg PO bid) + paclitaxel 80 mg/ m2 + carboplatin AUC=2 (12 weekly cycles) + (filgrastim) followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 (4 cycles every 3 weeks) + (pegfilgrastim). Eligibility: Women ≥ 18 years old with clinical stage IIB or stage IIIA, IIIB, or IIIC untreated TNBC (ER <1% , PR <1% , Her-2/neu 0, 1+ on IHC or 2+ and FISH ratio < 1.8) are eligible. Correlative Studies: Correlation of pCR with tissue expression of CK5, EGFR, ERCC1, Ki-67, Parp1, and longitudinal enumeration of CTCs will be done. Exploratory tissue biomarkers with prognostic and predictive value will be correlated with pCR. Enrollment: The trial will begin accrual in February 2013.

scholarly journals TBCRC009: A Multicenter Phase II Clinical Trial of Platinum Monotherapy With Biomarker Assessment in Metastatic Triple-Negative Breast Cancer

2015 ◽  
Vol 33 (17) ◽  
pp. 1902-1909 ◽  
Author(s):  
Steven J. Isakoff ◽  
Erica L. Mayer ◽  
Lei He ◽  
Tiffany A. Traina ◽  
Lisa A. Carey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Trial ◽  
Homologous Recombination ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Phase Ii Clinical Trial ◽  
End Points ◽  
Homologous Recombination Deficiency

Purpose The identification of patients with metastatic triple-negative breast cancer (mTNBC) who are expected to benefit from platinum-based chemotherapy is of interest. We conducted a single-arm phase II clinical trial of single-agent platinum for mTNBC with biomarker correlates. Patients and Methods Patients with mTNBC received first- or second-line cisplatin (75 mg/m2) or carboplatin (area under the concentration-time curve 6) by physician's choice once every 3 weeks. Coprimary end points were objective response rate (RR) and response prediction by p63/p73 gene expression. Secondary and exploratory end points included toxicity assessment, RR in cisplatin versus carboplatin, and RR in molecularly defined subgroups, including BRCA1/2 mutation carriers. Results Patients (N = 86; 69 as first-line therapy) received cisplatin (n = 43) or carboplatin (n = 43). RR was 25.6% (95% CI, 16.8% to 36%) and was numerically higher with cisplatin (32.6%) than with carboplatin (18.7%). RR was 54.5% in patients with germline BRCA1/2 mutations (n = 11). In patients without BRCA1/2 mutations (n = 66), exploratory analyses showed that a BRCA-like genomic instability signature (n = 32) discriminated responding and nonresponding tumors (mean homologous recombination deficiency–loss of heterozygosity/homologous recombination deficiency–large-scale state transitions [HRD-LOH/HRD-LST] scores were 12.68 and 5.11, respectively), whereas predefined analysis by p63/p73 expression status (n = 61), p53 and PIK3CA mutation status (n = 53), or PAM50 gene expression subtype (n = 55) did not. Five of the six long-term responders alive at a median of 4.5 years lacked germline BRCA1/2 mutations, and two of them had increased tumor HRD-LOH/HRD-LST scores. Conclusion Platinum agents are active in mTNBC, especially in patients with germline BRCA1/2 mutations. A measure of tumor DNA repair function may identify patients without mutations who could benefit from platinum therapy agents. Prospective controlled confirmatory trials are warranted.

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