NSABP B-43: A phase III clinical trial to compare trastuzumab (T) given concurrently with radiation therapy (RT) to RT alone for women with HER2+ DCIS resected by lumpectomy (Lx).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS666-TPS666
Author(s):  
Melody A. Cobleigh ◽  
Stewart J. Anderson ◽  
Thomas B. Julian ◽  
Kalliopi P. Siziopikou ◽  
Douglas W. Arthur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Tumor Biology ◽  
Cancer Recurrence ◽  
Breast Conserving Surgery ◽  
Distant Recurrence ◽  
Phase Iii ◽  
Cytotoxicity Activity ◽  
Hazard Reduction ◽  
Noncompliance Rate

TPS666 Background: A significant amount of DCIS is ER-negative and/or overexpresses HER2. This study will test HER2-targeted therapy in DCIS. Among T-treated HER2+ patients (pts) with DCIS treated with a single dose of T, T is found in ductal aspirates and antibody-dependent cell-mediated cytotoxicity activity for HER2 is increased. T boosts the effectiveness of RT in breast cancer xenograft models and cell lines. T given during whole breast irradiation (WBI) may improve results for HER2+ DCIS treated with lumpectomy (Lx). A trial to examine this question will enhance the understanding of breast tumor biology, the prevention of such tumors, and could possibly extend breast-conserving surgery benefits for women with DCIS. Methods: After Lx for pure DCIS, each pt’s DCIS lesion is centrally tested for HER2 using ASCO/CAP guidelines. HER2+ pts are randomly assigned to receive 2 doses of T, 3 weeks apart during WBI or to WBI alone. Women ≥18 yrs with a margin-clear Lx for pure DCIS, with ECOG status 0/1 who are clinically or pathologically node negative are eligible. ER and/or PR status must be known before random assignment. Primary aims are to determine if T decreases ipsilateral breast cancer (IBC) recurrence, ipsilateral skin cancer recurrence, or ipsilateral DCIS. Secondary aims are to determine the benefit of T in preventing regional or distant recurrence and contralateral invasive breast cancer or DCIS. B-43 will determine if DFS, recurrence-free interval, and/or overall survival can be improved with the use of T. 2000 pts will be accrued over 7.9 yrs, with a definitive analysis of primary endpoints performed at163 IBC events (7.5 - 8 yrs after protocol initiation) with an 80% power to detect a hazard reduction of 36%, from 1.73 IBC events per 100 pt-yrs to 1.11 events per 100 pt-yrs. The 36% observed reduction in the hazard of IIBCR-SCR-DCIS on the T arm is based on a projection of 40% hazard reduction if the compliance were perfect, with a 10% noncompliance rate. As of 1-1-13, 1,127 pts have been randomized into the study. Support: PHS NCI-U10-CA-69651, -12027, and -P30-CA-14599 from the US NCI, and Genentech, Inc. Clinical trial information: NCT00769379.

A phase III clinical trial to compare trastuzumab (T) given concurrently with radiation therapy (RT) to RT alone for women with HER2+ DCIS resected by lumpectomy (Lx): NSABP B-43.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS657-TPS657
Author(s):  
Melody A. Cobleigh ◽  
Stewart J. Anderson ◽  
Thomas B. Julian ◽  
Kalliopi P. Siziopikou ◽  
Douglas W. Arthur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Agent ◽  
Tumor Biology ◽  
Cancer Recurrence ◽  
Breast Conserving Surgery ◽  
Molecular Therapy ◽  
Phase Iii ◽  
Fish Analysis ◽  
Ipsilateral Breast ◽  
Hazard Reduction

TPS657 Background: Asignificant amount of DCIS is ER negative and/or overexpresses HER2. This provides an opportunity to test molecular therapy in DCIS. In xenograft models and cell lines, T boosts RT effectiveness. In T-treated HER2+ patients, apoptosis occurs within 1 wk of single agent T use, with T found in ductal aspirates. Ample safety evidence for T exists. T given during whole breast irradiation (WBI) may improve results for Lx-resected HER2+ DCIS. A trial to examine this question will enhance the understanding of breast tumor biology and the prevention of such tumors and could possibly extend breast-conserving surgery benefits for women with DCIS. Methods: After Lx for pure DCIS, each patient’s DCIS lesion is centrally tested for HER2 by IHC analysis. HER2 2+ tumors undergo FISH analysis. HER2 3+ or FISH+ patients can be randomly assigned to 2 doses of T, 3 weeks apart during WBI or to WBI alone. Women ≥18 yrs. with a margin-clear Lx for pure DCIS, with ECOG status 0/1 who are and clinically or pathologically node negative are eligible. Centrally tested DCIS must be HER2 +. ER and/or PR status must be known before randomization. Primary aims are to determine if T decreases ipsilateral breast cancer recurrence, ipsilateral skin cancer recurrence, or ipsilateral DCIS. Secondary aims are to determine the benefit of T in preventing regional or distant recurrence and contralateral invasive breast cancer or DCIS. B-43 will determine if DFS, recurrence-free interval, and OS can be improved with the use of T. 2000 patients will be accrued over 7.9 yrs, with a definitive analysis of primary endpoints performed at163 ipsilateral breast cancer events (7.5 - 8 yrs. after protocol initiation) with an 80% power to detect a hazard reduction of 36%, from 1.73 ipsilateral breast cancer events per 100 pt-yrs to 1.11 events per 100 pt-yrs. The 36% observed reduction in the hazard of IIBCR-SCR-DCIS on the T arm is based on a projection of 40% hazard reduction if the compliance were perfect, with a 10% noncompliance rate. As of 12-31-11, 763 patients have been randomized. NCT00769379 Grant support: PHS NCI-U10-CA-69651, -12027, and NCI P30-CA-14599 from the US NCI and Genentech, Inc.

Primary results, NRG Oncology/NSABP B-35: A clinical trial of anastrozole (A) versus tamoxifen (tam) in postmenopausal patients with DCIS undergoing lumpectomy plus radiotherapy.

2015 ◽  
Vol 33 (18_suppl) ◽  
pp. LBA500-LBA500 ◽  
Author(s):  
Richard G. Margolese ◽  
Reena S. Cecchini ◽  
Thomas B. Julian ◽  
Patricia A. Ganz ◽  
Joseph P. Costantino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Distant Recurrence ◽  
Phase Iii ◽  
Resection Margins ◽  
Second Primary ◽  
Second Primary Cancers ◽  
Point Estimates ◽  
Secondary Endpoints

LBA500 Background: The primary endpoint of NSABP B-35, a phase III trial comparing 1 mg/day anastrozole to 20 mg/day tamoxifen, each given for 5 years, was breast cancer-free interval (BCFI), defined as the time from randomization to any breast cancer (BC) event including local, regional, or distant recurrence or contralateral disease, invasive or DCIS. Methods: Postmenopausal women with ER-receptor or PgR-receptor positive (by IHC analysis) DCIS and no invasive BC who had undergone a lumpectomy with clear resection margins were randomly assigned to receive either 20 mg/day tam or 1 mg/day A (blinded) for 5 years. Stratification was by age (<60 v ≥60). Results: From 1/6/2003 to 6/15/2006, 3,104 pts were entered and randomized (1552 in groups tam and A each). As of 2/28/15, follow-up information was available on 3,083 pts for OS and on 3,077 pts for all other disease-free endpoints, with mean time of follow-up of 8.6 years. There were 198 BCFI events, 114 in the tam group and 84 in the A group (HR, 0.73; p=0.03). 10-year point estimates for BCFI were 89.2% for tam and 93.5% for A. A significant time-by-treatment interaction (p=0.02) indicated that the effect was not evident until later in the study. There was a significant interaction between treatment and age group (p=0.04); benefit of A is only in women <60 years old. As to secondary endpoints, there were 495 DFS events, 260 in the tam group and 235 in the A group (HR, 0.89; p=0.21). 10-year point estimates for DFS were 77.9% for tam and 82.7% for A. There were 186 deaths, 88 in the tam group and 98 in the A group (HR, 1.11; p=0.48). 10-year point estimates for OS were 92.1% for tam, 92.5% for A. There were 8 deaths due to breast cancer in the tam group and 5 in the A group. There were 63 cases of invasive breast cancer in the tam group and 39 in the A group (HR, 0.61; p=0.02). There was a non-significant trend for a reduction in breast second primary cancers with A (HR, 0.68; p=0.07). Conclusions: Anastrozole provided a significant improvement compared to tamoxifen for BCFI, which was seen later in the study, primarily in women <60 years. Support: CA12027, 37377, 69651, 69974; 180868, 180822, 189867 196067, 114732; AstraZeneca Pharmaceuticals LP. Clinical trial information: NCT00053898.

scholarly journals Efficacy and Safety Analysis of Nelipepimut-S Vaccine to Prevent Breast Cancer Recurrence: A Randomized, Multicenter, Phase III Clinical Trial

2019 ◽  
Vol 25 (14) ◽  
pp. 4248-4254 ◽  
Author(s):  
Elizabeth A. Mittendorf ◽  
Biao Lu ◽  
Michelle Melisko ◽  
Julie Price Hiller ◽  
Igor Bondarenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Cancer Recurrence ◽  
Safety Analysis ◽  
Breast Cancer Recurrence ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Phase Iii Clinical Trial ◽  
Multicenter Phase

scholarly journals Retrospective, Multicenter Analysis Comparing Conventional with Oncoplastic Breast Conserving Surgery: Oncological and Surgical Outcomes in Women with High-Risk Breast Cancer from the OPBC-01/iTOP2 Study

2021 ◽  
Author(s):  
Florian Fitzal ◽  
Michael Bolliger ◽  
Daniela Dunkler ◽  
Angelika Geroldinger ◽  
Luca Gambone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Local Control ◽  
Tumor Biology ◽  
Survival Rates ◽  
Breast Conservation ◽  
Breast Conserving Surgery ◽  
Distant Recurrence ◽  
Resection Margins

Abstract Introduction Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4). Methods Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. Results A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 (“ink on tumor”) in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. Conclusions Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI.

scholarly journals Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Andrea DeCensi ◽  
Harriet Johansson ◽  
Thomas Helland ◽  
Matteo Puntoni ◽  
Debora Macis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Low Dose ◽  
Cancer Recurrence ◽  
Phase Iii ◽  
Cyp2d6 Genotype ◽  
Phase Iii Trial ◽  
Reactive Protein ◽  
Non Invasive ◽  
Tamoxifen Metabolites ◽  
Dose Trial

AbstractLow-dose tamoxifen halves recurrence in non-invasive breast cancer without significant adverse events. Some adjuvant trials with tamoxifen 20 mg/day had shown an association between low endoxifen levels (9–16 nM) and recurrence, but no association with CYP2D6 was shown in the NSABP P1 and P2 prevention trials. We studied the association of CYP2D6 genotype and tamoxifen metabolites with tumor biomarkers and recurrence in a randomized phase III trial of low-dose tamoxifen. Median (IQR) endoxifen levels at year 1 were 8.4 (5.3–11.4) in patients who recurred vs 7.5 (5.1–10.2) in those who did not recur (p = 0.60). Tamoxifen and metabolites significantly decreased C-reactive protein (CRP, p < 0.05), and a CRP increase after 3 years was associated with higher risk of recurrence (HR = 4.37, 95% CI, 1.14–16.73, P = 0.03). In conclusion, endoxifen is below 9 nM in most subjects treated with 5 mg/day despite strong efficacy and there is no association with recurrence, suggesting that the reason for tamoxifen failure is not poor drug metabolism. Trial registration: ClinicalTrials.gov, Identifier: NCT01357772.

Sign in / Sign up

Export Citation Format

Share Document