Safety and efficacy of single-agent adjuvant trastuzumab in older women with early-stage breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 528-528
Author(s):  
Cynthia Owusu ◽  
Seunghee P Margevicius ◽  
Heidi D. Klepin ◽  
Charles L. Vogel ◽  
Asrar Alahmadi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Women ◽  
Cumulative Incidence ◽  
Single Agent ◽  
Metastatic Breast ◽  
Stage I ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
One Year ◽  
Positive Breast Cancer

528 Background: Older adults with multiple comorbidities and poor functional status may not be appropriate candidates for chemotherapy. We conducted a phase II trial to examine the safety and efficacy of single-agent Trastuzumab for older women with early stage Human Epidermal Growth Factor Receptor Type 2 (Her2)-positive breast cancer. Methods: This was a single-arm open label multi-institutional clinical trial of adjuvant single-agent Trastuzumab in women aged ≥ 60 years with stage I-III Her2-positive breast cancer who had either declined chemotherapy or were not chemotherapy candidates. Patients received Trastuzumab monotherapy, (8 mg/kg) for cycle 1 followed by (6 mg/kg) every 3 weeks for 12 months. The primary end point was one-year cumulative incidence of symptomatic congestive heart failure with reduced ejection fraction (HFrEF). Secondary endpoints were disease free survival (DFS) and overall survival (OS) at 5 years. Results: Fifty-six patients were enrolled across four centers with a median follow-up period of 5.0 years, (range 0-6.5). The median age was 72.5 years (range 60-90), 64% had stage I disease, 77% had estrogen-receptor positive disease and 82% had node-negative breast cancer. Only two patients had symptomatic congestive HFrEF with a one-year cumulative incidence of 3.6%; (95% confidence interval [CI], 0.09 to 13.8). Five patients had asymptomatic declines in ejection fraction with a one-year cumulative incidence of 9.1%; (95% CI, 3.9 to 20.1). The 5-year DFS was 86.4%; (95% CI, 73.6 to 93.3). Among seven relapses seen, two were due to distant metastatic breast cancer. The 5-year rate of overall survival was 90.2%; (95% CI, 78.1 to 95.8). Among five deaths, one was due to distant metastatic breast cancer. Conclusions: Among older women with stage I-III HER2-positive breast cancer who decline chemotherapy or are not chemotherapy candidates, treatment with her2 targeted therapy only without chemotherapy may offer a reasonable treatment option without an inordinate rate of cardiac toxicity. Clinical trial information: NCT00796978 .

scholarly journals Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takahiro Nakayama ◽  
Tetsuhiro Yoshinami ◽  
Hiroyuki Yasojima ◽  
Nobuyoshi Kittaka ◽  
Masato Takahashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Observational Study ◽  
Real World ◽  
Metastatic Breast ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
The Real ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Abstract Background Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post–T-DM1 treatments is currently lacking. We evaluated the effectiveness of post–T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer. Methods In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post–T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken. Results Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval [CI]) rwPFS, TTF, and OS were 5.7 (4.8–6.9) months, 5.6 (4.6–6.4) months, and 22.8 (18.2–32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8–56.7) and 23% (15.1–31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, ≥12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months. Conclusions In the real-world setting in Japan, several post–T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings. Trial registration UMIN000038296; registered on 15 October 2019.

scholarly journals A US Registry–Based Assessment of Use and Impact of Chemotherapy in Stage I HER2-Positive Breast Cancer

2018 ◽  
Vol 16 (11) ◽  
pp. 1311-1320 ◽  
Author(s):  
Benjamin M. Parsons ◽  
Dipesh Uprety ◽  
Angela L. Smith ◽  
Andrew J. Borgert ◽  
Leah L. Dietrich
Keyword(s):  
Breast Cancer ◽  
Stage I ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Trastuzumab deruxtecan in previously treated HER2-positive metastatic breast cancer: Plain language summary of the DESTINY-Breast01 study

2021 ◽  
Author(s):  
Shanu Modi
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Metastatic Breast ◽  
Common Adverse Event ◽  
The Body ◽  
Plain Language ◽  
Her2 Positive ◽  
Serious Adverse Events ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

This is a summary of the article discussing the results of the DESTINY-Breast01 study originally published in the New England Journal of Medicine. The DESTINY-Breast01 study is a clinical study in participants with a type of breast cancer called HER2-positive breast cancer. The participants in the study received a treatment called trastuzumab deruxtecan, also known as T-DXd. The purpose of this summary is to help you understand the results of the DESTINY-Breast01 study. T-DXd is currently available as a treatment for adults with HER2-positive breast cancer that cannot be removed by surgery, also called unresectable, or that has spread, also called metastatic. In the DESTINY-Breast01 study, all the participants had HER2-positive breast cancer that was metastatic or unresectable. All participants were required to have had previous treatment for their HER2-positive breast cancer with another treatment, called trastuzumab emtansine or T-DM1. All the participants received T-DXd every 3 weeks. Part 1 was done to learn how T-DXd acted in the body, and to choose a dose to give to all the participants in Part 2. In Part 2, 184 participants received T-DXd at 5.4 mg/kg and the results showed that T-DXd reduced tumor growth. Up to 60.9% of the participants had their tumors shrink or disappear, with a treatment response that lasted for nearly 15 months on average. The participants lived with their cancer for around 16 months before it got worse. During the study, 183 out of 184 participants had side effects, known as adverse events. The most common adverse event was nausea. There were 42 participants (22.8%) who had serious adverse events, including lung toxicity. These results suggest that T-DXd could be a treatment option for people with metastatic HER2-positive breast cancer who have already been treated with T-DM1. Additional studies will provide more information and results about T-DXd. ClinicalTrials.gov NCT number: NCT03248492 To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Link to original article here .

De-escalating adjuvant trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer: A systemic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 524-524
Author(s):  
Hadar Goldvaser ◽  
Korzets Ceder Yasmin ◽  
Daniel Shepshelovich ◽  
Rinat Yerushalmi ◽  
Michal Sarfaty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardiac Dysfunction ◽  
Early Stage ◽  
Nodal Involvement ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Trastuzumab Treatment ◽  
Her2 Positive Breast Cancer ◽  
One Year ◽  
Positive Breast Cancer

524 Background: One year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage HER2 positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results. Methods: A search of PubMed and conferences identified randomized trials that compared abbreviated trastuzumab therapy to one year of treatment in early-stage HER2 positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for disease free survival (DFS) and overall survival (OS). Data on the number of DFS and distant relapse events were also collected as were the number of patients at risk in each group. Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor (ER) expression and the duration of abbreviated trastuzumab (9-12 weeks versus 6 months). Odds ratios (ORs) and 95% CI were computed for pre-specified cardiotoxicity events including cardiac dysfunction and congestive heart failure (CHF). Results: Analysis included 6 trials comprising 11603 patients. In most studies adjuvant chemotherapy included anthracyclines and taxanes. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI 1.05-1.25, p = 0.002) and OS (HR = 1.15, 95% CI 1.02-1.29. p = 0.02). The effect on DFS was not influenced by ER status (p for the subgroup difference = 0.23), nodal involvement (p = 0.44) or the different duration of trastuzumab in the experimental arm (p = 0.08). In absolute terms, after an estimated median follow-up of 71 months, shorter treatment with trastuzumab was associated with an absolute increase in DFS events of 2.3%. Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI 0.55-0.81, p < 0.001) and CHF (OR = 0.66, 95% CI 0.50-0.86, p = 0.003). Conclusions: Compared to one year, shorter duration of adjuvant trastuzumab is associated with significantly worse DFS and OS, despite favorable cardiotoxicity profile. One year of trastuzumab should remain the standard adjuvant treatment in early-stage HER2 positive breast cancer with appropriate cardiac monitoring.

scholarly journals Targeting Cancer Stem Cells and Metastasis with Epigenetic Modulation and Anti-HER2 Therapy: Phase I/II Trial of Vorinostat in Combination with Lapatinib

2020 ◽  
pp. 1-12
Author(s):  
Saranya Chumsri ◽  
Amanda Schech ◽  
Angela Brodie ◽  
Jane Lewis ◽  
Katherine Tkaczuk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Phase I ◽  
Single Agent ◽  
Preclinical Studies ◽  
Her2 Positive ◽  
Mesenchymal Transition ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Purpose: Considerable preclinical and clinical data indicate that only a small subset of tumor cells has longterm proliferating capacity. These cells are termed cancer stem cells (CSCs). Failure to eradicate CSCs is hypothesized to be a cause of cancer recurrence after potentially curative therapies. Therefore, approaches that target CSCs have the potential to improve outcomes. We evaluated the combination of vorinostat and lapatinib to target CSCs and metastasis. Experimental Design: We conducted preclinical studies and a phase I/II clinical trial to determine the effects of vorinostat and lapatinib to CSCs. Results: Our preclinical studies demonstrated that vorinostat and lapatinib further reduced CSCs compared to either single agent. Reduction in self-renewal proteins, mammospheres, epithelial-mesenchymal transition (EMT) markers, and cell migration was also observed. Based on these findings, the combination was evaluated in the phase I trial to which a total of 12 patients were enrolled. Dose-limiting toxicity was not observed in phase I, and the recommended phase II dose was vorinostat 400 mg 4 days on 3 days off and lapatinib 1,250 mg daily. In HER2-positive breast cancer patients, the clinical benefit rate was observed in 43% of subjects. Interestingly, patients who remained on vorinostat and lapatinib did not develop any new site of metastasis. Conclusion: The combination of vorinostat and lapatinib is safe and active in HER2-positive breast cancer. Further studies are needed to evaluate this strategy to target CSCs and metastasis.

scholarly journals Do all patients with HER2 positive breast cancer require one year of adjuvant trastuzumab? A systematic review and meta-analysis

The Breast ◽  
2020 ◽  
Vol 54 ◽  
pp. 203-210
Author(s):  
Paul Stewart ◽  
Phillip Blanchette ◽  
Prakesh S. Shah ◽  
Xiang Y. Ye ◽  
R. Gabriel Boldt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Her2 Positive Breast Cancer ◽  
One Year ◽  
Positive Breast Cancer

Do all patients with HER2-positive breast cancer require one year of adjuvant trastuzumab?: A systematic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 522-522 ◽  
Author(s):  
Paul Stewart ◽  
Phillip S. Blanchette ◽  
Prakesh S Shah ◽  
Xiang Y Ye ◽  
R Gabriel Boldt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Her2 Positive Breast Cancer ◽  
Er Positive ◽  
One Year ◽  
Positive Breast Cancer

522 Background: One year of adjuvant trastuzumab (T) remains the standard treatment for patients with HER2 positive breast cancer. Results from randomized trials with diverse non-inferiority margins comparing one year to a shorter duration of adjuvant T were not consistent, particularly with the PERSEPHONE and the final PHARE and Short-HER trials’ results. Our objective was to conduct a systematic review and meta-analysis of randomized trials in patients with HER2 positive breast cancer to assess whether a shorter duration of adjuvant T was non-inferior to one year of treatment. Methods: PubMed, EMBASE and The Cochrane Library were searched for eligible randomized trials. Hazard ratios (HR) for disease free and overall survival (DFS, OS) were weighted using generic inverse variance and pooled in a meta-analysis using random-effects models. The median of non-inferiority margins derived from each trial was calculated to set a non-inferiority margin of 1.29 for the pooled analysis. Subgroup analyses compared survival outcomes by estrogen receptor (ER) status, nodal status, length and timing of trastuzumab treatment. Results: Data of 11,376 patients from 5 trials were analyzed. A shorter duration of T was non-inferior to one year of therapy for DFS (HR 1.13, 95%CI 1.03-1.24) but worse for OS (HR 1.16, 95%CI 1.01-1.32). In addition, the non-inferiority for DFS was met for patients with ER positive disease (HR 1.1, 95%CI 0.95-1.28) and patients treated with 6 months (HR 1.09, 95%CI 0.98-1.22) or sequential T (HR 0.97, 95%CI 0.75-1.27). Conversely, the non-inferiority for DFS was not met for patients with ER negative disease (HR 1.22, 95%CI 1.06-1.41), patients treated with 9 weeks (HR 1.26, 95%CI 1.02-1.55) or concomitant T (HR 1.25, 95%CI 1.07-1.45) and patients with node negative (HR 1.12, 95% 0.93-1.35) or positive (HR 1.16, 95%CI 0.99-1.36) disease. Conclusions: Within the limitations of the available data and the different non-inferiority margins used in randomized trials, a shorter duration of adjuvant T is non-inferior to one year of therapy for DFS in patients with HER2 positive breast cancer, particularly in patients with ER positive disease. Further trials with appropriately chosen non-inferiority margins are needed to confirm the optimal duration of T in patients with low-risk disease.

Sign in / Sign up

Export Citation Format

Share Document