Efficacy of epirubicin plus cyclophosphamide followed by taxanes versus carboplatin plus taxanes as adjuvant chemotherapy in triple-negative breast cancer: 8.1 years median follow-up on a randomized clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 529-529
Author(s):  
Fangchao Zheng ◽  
Feng Du ◽  
Yongsheng Wang ◽  
Xue Wang ◽  
Jiayu Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Triple Negative Breast Cancer ◽  
Adjuvant Treatment ◽  
Subgroup Analysis ◽  
Triple Negative ◽  
Brca Mutation ◽  
Disease Free Survival ◽  
Open Label

529 Background: Four cycles of adjuvant taxanes (paclitaxel or docetaxel) after four cycles of adjuvant doxorubicin plus cyclophosphamide (ECT) are considered a standard adjuvant treatment and improves survival outcomes of triple negative breast cancer (TNBC). The purpose of this analysis was to further assess whether adjuvant carboplatin plus taxanes (TP) was non-inferior to or superior to standard ECT chemotherapy in prolonging the survival time. Methods: This randomized, open-label, multicenter clinical trial conducted at three hospital in China from June, 2009 and October, 2015. Eligible early triple-negative breast cancer (TNBC) patients were randomized (1:1) to receive ECT (four cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2 followed by four cycles of docetaxel 75 mg/m2 or paclitaxel 175 mg/m2 every 3 weeks, ECT arm, n = 154) or receive TP (six cycles of docetaxel 75 mg/m2 or paclitaxel 175 mg/m2 + carboplatin AUC 5 every 3 weeks; TP arm, n = 154), which was then followed by surgery. Results: Three hundred and eight patients were recruited in this trial and final date of follow-up was January 20, 2021. Baseline characteristics were balanced between ECT arm and TP arm. Median follow-up was 97.6 months. Median disease free survival (DFS) was not reached; 8-year DFS rate was 78.35% with ECT arm and 81.73% with TP arm (hazard ratio [HR] = 0.84; 95% confidence interval [CI] = 0.50 - 1.40; P = 0.496). Median overall survival (OS) was also not reached; 8-year OS rate was 87.15% with ECT arm and 89.14% with TP arm (HR = 0.87; 95% CI = 0.44 - 1.70; P = 0.676). For TNBC patients with DFS > 4 year, TP arm had a longer DFS than ECT ( P = 0.01), and had a tendency with better OS ( P = 0.4). In this subgroup analysis of SPARC > 50%, TP arm had a longer DFS than ECT ( P < 0.05), and also had a tendency with better OS ( P = 0.06). In subgroup analysis of PD-1 (-) and intravascular invasion (+), TP arm had a better DFS ( P = 0.02) and OS ( P = 0.03) than ECT arm. DFS or OS had no significant differences in ECT and TP arm with BRCA mutation or BRCA wild ( all P values > 0.05). Conclusions: TP chemotherapy showed significant non-inferiority for PFS and OS versus ECT in the first-line adjuvant treatment of early TNBC. For some particular subgroup of TNBC, TP may be a more effective chemotherapy than ECT. TP may be considered an effective alternative to early TNBC. Clinical trial information: NCT01150513.

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 Adjuvant Capecitabine With Docetaxel and Cyclophosphamide Plus Epirubicin for Triple-Negative Breast Cancer (CBCSG010): An Open-Label, Randomized, Multicenter, Phase III Trial

2020 ◽  
Vol 38 (16) ◽  
pp. 1774-1784 ◽  
Author(s):  
Junjie Li ◽  
Keda Yu ◽  
Da Pang ◽  
Changqin Wang ◽  
Jun Jiang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Safety Data ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Control Treatment ◽  
Open Label ◽  
Phase Iii Trial ◽  
Grade 3

PURPOSE Standard adjuvant chemotherapy for triple-negative breast cancer (TNBC) includes a taxane and an anthracycline. Concomitant capecitabine may be beneficial, but robust data to support this are lacking. The efficacy and safety of the addition of capecitabine into the TNBC adjuvant treatment regimen was evaluated. PATIENTS AND METHODS This randomized, open-label, phase III trial was conducted in China. Eligible female patients with early TNBC after definitive surgery were randomly assigned (1:1) to either capecitabine (3 cycles of capecitabine and docetaxel followed by 3 cycles of capecitabine, epirubicin, and cyclophosphamide) or control treatment (3 cycles of docetaxel followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide). Randomization was centralized without stratification. The primary end point was disease-free survival (DFS). RESULTS Between June 2012 and December 2013, 636 patients with TNBC were screened, and 585 were randomly assigned to treatment (control, 288; capecitabine, 297). Median follow-up was 67 months. The 5-year DFS rate was higher for capecitabine than for control treatment (86.3% v 80.4%; hazard ratio, 0.66; 95% CI, 0.44 to 0.99; P = .044). Five-year overall survival rates were numerically higher but not significantly improved (capecitabine, 93.3%; control, 90.7%). Overall, 39.1% of patients had capecitabine dose reductions, and 8.4% reported grade ≥ 3 hand-foot syndrome. The most common grade ≥ 3 hematologic toxicities were neutropenia (capecitabine, 136 [45.8%]; control, 118 [41.0%]) and febrile neutropenia (capecitabine, 50 [16.8%]; control, 46 [16.0%]). Safety data were similar to the known capecitabine safety profile and generally comparable between arms. CONCLUSION Capecitabine when added to 3 cycles of docetaxel followed by 3 cycles of a 3-drug anthracycline combination containing capecitabine instead of fluorouracil significantly improved DFS in TNBC without new safety concerns.

A randomized, triple negative breast cancer enrolling trial to confirm molecular profiling improves survival (ARTEMIS).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS590-TPS590 ◽  
Author(s):  
Clinton Yam ◽  
Kenneth R. Hess ◽  
Jennifer Keating Litton ◽  
Wei Tse Yang ◽  
Helen Piwnica-Worms ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Triple Negative Breast Cancer ◽  
Primary Tumor ◽  
Triple Negative ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Type I ◽  
Free Survival

TPS590 Background: Following neoadjuvant chemotherapy (NACT), patients (pts) with triple negative breast cancer (TNBC) achieving pathologic complete response/residual cancer burden-0 (pCR/RCB-0) or minimal residual disease (RCB-I) have an improved relapse free survival when compared to pts with more extensive residual disease (RCB-II/III) (Symmans et al, JCO 2017). Pts with chemo-resistant TNBC have a poor prognosis as there are currently no FDA-approved targeted agents available for TNBC. We previously reported the ability of a novel gene expression signature (GES) to predict sensitivity to NACT (Hatzis et al, JAMA 2011). Here we seek to prospectively validate the use of this GES in combination with imaging to predict response to NACT and establish the clinical impact of selecting pts predicted to have non-responsive disease (NRD) for enrollment in clinical trials of targeted therapy. Methods: All pts will undergo a biopsy of the primary tumor for molecular characterization (MC) and will be randomized 2:1 to know their MC results (intervention arm) or not (control arm). A maximum of 360 pts will be enrolled and randomized using a group sequential design with one-sided O’Brien-Fleming boundaries, with two equally spaced binding interim tests for futility and superiority and one final test, having an overall Type I error of 0.05 and power of 0.80 to detect an improvement in pCR/RCB-I from 50% to 64%. Secondary endpoints include rates of clinical trial enrollment, disease free survival and integrated biomarker analyses. All pts will receive 4 cycles of anthracycline-based NACT with imaging done every 2 cycles to assess response. After completion or progression on anthracycline-based NACT, pts predicted to have NRD based on MC/imaging (intervention arm) or imaging alone (control arm) will be offered enrollment on a clinical trial. Pts are eligible if they have stage I-III TNBC with a primary tumor that is ≥1.5cm. Pts with contraindications to anthracyclines and/or taxanes are excluded. Enrollment began in November 2015. 105 pts have been enrolled to date with 71 and 34 pts randomized to the intervention and control arms, respectively. Clinical trial information: NCT02276443.

Pathological complete response rate and survival in patients with BRCA-associated triple-negative breast cancer after 12 weeks of de-escalated neoadjuvant chemotherapy: Translational results of the WSG-ADAPT TN randomized phase II trial (NCT01815242).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 579-579
Author(s):  
Lisa Katharina Katharina Richters ◽  
Oleg Gluz ◽  
Nana Weber-Lassalle ◽  
Matthias Christgen ◽  
Heinz Haverkamp ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Phase Ii Trial ◽  
Brca Mutation ◽  
Complete Response ◽  
Mutation Status

579 Background: The phase II trial WSG-ADAPT TN randomized triple-negative breast cancer (TNBC) patients to receive 12 weeks of neoadjuvant nab-paclitaxel (nab-pac) combined with carboplatin (carbo) vs gemcitabine (gem) and showed a substantial improvement of pathological complete response (pCR: ypT0/is, ypN0) with carbo (45.9% vs 28.7%). pCR had a strong favorable impact on iDFS after 3-year follow-up. Distribution of tumor mutations in BC-associated genes and impact of BRCA mutation status on pCR and outcome are analyzed here. Methods: NGS-based mutational analysis of BRCA1/2 and 18 further (potentially) BC-associated genes was performed on DNA derived from pretreatment FFPE samples (gem: n = 158, carbo: n = 108) using a customized gene panel. Variants with a variant fraction of ≥5% were included and classified according to IARC and ENIGMA guidelines. Results: In 42 of the 266 analyzed samples, at least one deleterious BRCA1/2-variant was found (15.8%; BRCA1 n = 37, BRCA2 n = 3, BRCA1+ BRCA2 n = 2) one of which displayed an additional STK11-mutation. In the BRCA1/2-negative cohort, a mutation in one of 14 further analyzed (potential) BC-risk genes was found in 19 samples (7.1%; BARD1 n = 3, CHEK2 n = 2, CDH1 n = 2, FANCM n = 3, PALB2 n = 5, RAD50 n = 1, RAD51C n = 1, RAD51D n = 1, XRCC2 n = 1; no deleterious mutations were found in ATM, BRIP1, MRE11A, NBN). At least one deleterious variant in TP53, PIK3CA, PTEN or MAP3K1 was seen in 89.1% (n = 237; TP53 n = 233, PIK3CA n = 22 PTEN n = 15, MAP3K1 n = 1). In 22 samples (8.3%) no deleterious mutation was identified in the analyzed genes. Overall, patients with tumor BRCA mutation (carbo n = 14, gem n = 28) had 45.2% vs 34.4% pCR (OR = 1.58, 95%-CI: 0.81-3.07, p =.18) without a mutation. pCR in the small group with mutation receiving carbo (n = 14) was 64.3% vs. 34.5% in all others (OR = 3.41, 95%-CI: 1.11-10.50; p =.03); direct comparison to BRCA-positive patients receiving gem (n = 28, 35.7%, OR = 3.2, 95%-CI: 0.85-12.36, p = 0.079) did not reach statistical significance. The results suggest that the strong favorable impact of pCR on iDFS is preserved even among BRCA-positive patients (n = 42, p =.07), as well as in the BRCA-negative subgroup (p <.001). No evidence for a predictive impact of BRCA mutation on efficacy of 4xEC additional chemotherapy was seen overall or within pCR subgroups. Conclusions: Twelve weeks of neoadjuvant nab-pac/carbo is a highly effective anthracycline-free regimen that leads to an excellent pCR-rate of 64% in tumor BRCA1/2-mutated cases. BRC A1/2 mutation status could support this de-escalation strategy in early TNBC, but further prospective validation of survival impacts in larger cohorts and with longer follow up is needed. More detailed survival analyses will be presented at the meeting. Clinical trial information: NCT01815242.

The Head to Head trial: Letrozole vs anastrozole as adjuvant treatment of postmenopausal patients with node positive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10672-10672 ◽  
Author(s):  
R. De Boer ◽  
H. A. Burris ◽  
A. Monnier ◽  
H. Mouridsen ◽  
J. A. O’Shaughnessy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Safety Data ◽  
Disease Free Survival ◽  
Her2 Status ◽  
Open Label ◽  
Specific Patient ◽  
Risk Of Recurrence ◽  
Cancer Data

10672 Introduction: Aromatase Inhibitors (AIs) have demonstrated both efficacy and safety advantages over tamoxifen (T) in all treatment settings in breast cancer (BC) and are becoming the new standard of care as endocrine therapy for postmenopausal patients (PM) with BC. Rationale: Cumulative evidence suggests that all AIs may not be the same, raising the question of whether there is a superior AI, and whether any specific patient populations derive differing degrees of benefit from a particular AI. In the ATAC trial, evaluating anastrozole (A) in PM patients with early breast cancer (EBC), at 33 months median follow up the risk of recurrence in the hormone receptor positive (HR+) population was reduced by 22%.The BIG 1–98 Trial, evaluating letrozole (L) in PM women with EBC, showed a significant benefit in favor of L over T at a median follow up of 26 months, with a 19% reduction in the risk of recurrence; in subgroup analyses, L significantly decreased the risk of recurrence in LN+ patients and in patients who received adjuvant chemotherapy. This study is a head to head comparison of L and A in HR+, LN+ PM patients with EBC and aims to compare L vs A in the adjuvant treatment of these patients. Design and Methods: This is a Phase IIIb open-label, randomized, multicentre study including 4000 PM patients from up to 250 international sites. PM patients with HR+, LN+ BC who have recently undergone surgery for primary BC will be randomized to either receive L 2.5 mg or A 1 mg daily. Treatment will commence following completion of standard chemotherapy (if given) and concurrently with radiotherapy (if given)Patients will receive treatment until disease recurrence/relapse for up to 5 years. Patients will be stratified by number of LN and HER2 status. The primary objective is disease free survival at 5 years for L and A. Secondary objectives include safety, overall survival, time to distant metastases and time to contralateral breast cancer. Data analysis will be conducted by an independent group of investigators. Summary: Updated patient accrual figures, including any available early safety data, will be presented at the meeting. No significant financial relationships to disclose.

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.

scholarly journals Comprehensive Genomic Profile of Heterogeneous Long Follow-Up Triple-Negative Breast Cancer and Its Clinical Characteristics Shows DNA Repair Deficiency Has Better Prognostic

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1367
Author(s):  
Ernesto Rojas-Jiménez ◽  
Javier César Mejía-Gómez ◽  
Clara Díaz-Velásquez ◽  
Rosalía Quezada-Urban ◽  
Héctor Martínez Gregorio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Latin American ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Genomic Alterations ◽  
Driver Genes

Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies.

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial

2021 ◽  
Vol 22 (4) ◽  
pp. 499-511 ◽  
Author(s):  
Eric P Winer ◽  
Oleg Lipatov ◽  
Seock-Ah Im ◽  
Anthony Goncalves ◽  
Eva Muñoz-Couselo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Phase

scholarly journals Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer (“METRIC”): a randomized multicenter study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Linda T. Vahdat ◽  
Peter Schmid ◽  
Andres Forero-Torres ◽  
Kimberly Blackwell ◽  
Melinda L. Telli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Primary Endpoint ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Common Grade ◽  
Open Label Phase ◽  
Grade 3

AbstractThe METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.

Sign in / Sign up

Export Citation Format

Share Document