registHER: Baseline characteristics of a cohort of HER2-positive metastatic breast cancer (MBC) patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20095-20095
Author(s):  
P. Kaufman ◽  
M. Mayer ◽  
S. Paik ◽  
M. Ulcickas Yood ◽  
D. Yardley ◽  
...  
Keyword(s):  
Diagnostic Testing ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Breast Cancers ◽  
Pivotal Trial ◽  
Her2 Positive ◽  
Estrogen Receptor Positive ◽  
Treatment Data ◽  
Baseline Characteristics ◽  
Study Sites

20095 Background: HER2 is amplified in 25% of breast cancers and is associated with poor survival. registHER captures the natural history, treatment patterns and outcomes in 1000 newly-diagnosed HER2-positive MBC patients (pts) throughout the U.S. This observational study recruits pts in both academic and community centers. Methods: This ongoing prospective cohort study collects clinical, pathologic and treatment data at enrollment, quarterly until death, loss to follow-up or 3 years after the last enrollment. We describe baseline pt and clinical characteristics in registHER compared with HER2-positive MBC pts in the phase III pivotal trial (Slamon DJ, et al. N Engl J Med. 2001;344:783–792). Results: Between December 2003 and September 2005, 813 eligible pts were enrolled at 280 study sites. Most pts were seen at community-based (76%) vs academic (18%) clinics; a few pts did not fall into either category (6%). A comparison of baseline characteristics is shown below. Conclusions: registHER pts tended to have a shorter disease-free interval and more estrogen receptor positive disease than pts in the pivotal trial. Reasons for these differences could reflect trial referral and/or diagnostic testing differences. Fewer registHER patients were white, but other characteristics were similar between the two groups. These findings support the hypothesis that observational studies describe a broad patient population which may not exactly duplicate clinical trials. Within registHER, there was some variation between academic vs community clinics (eg. nodal status and adjuvant therapy). Treatment pattern analyses are ongoing. [Table: see text] [Table: see text]

Ado-trastuzumab Emtansine

2014 ◽  
Vol 48 (11) ◽  
pp. 1484-1493 ◽  
Author(s):  
Patricia A. Corrigan ◽  
Teresa A. Cicci ◽  
Jessica Johnston Auten ◽  
Denise K. Lowe
Keyword(s):  
Clinical Trials ◽  
English Language ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Tolerability Profile ◽  
Trastuzumab Emtansine ◽  
Breast Cancers ◽  
Sources Of Information ◽  
Antibody Drug Conjugate ◽  
Her2 Positive

Objective: To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug-drug interactions, dosage and administration, and formulary considerations for ado-trastuzumab emtansine. Data Sources: Sources of information were identified through a PubMed search (1966 to June 2014) using the key terms ado-trastuzumab emtansine, trastuzumab-DM1, trastuzumab-MCC-DM1, and T-DM1. Other information was obtained from clinicaltrials.gov, product labeling, and press releases. Study Selection and Data Extraction: All English-language clinical trials and abstracts evaluating ado-trastuzumab emtansine in humans were reviewed for inclusion. Data Synthesis: Overexpression or amplification of human epidermal growth factor receptor 2 (HER2) occurs in approximately 20% of breast cancers and is associated with more aggressive tumors and poorer prognosis in the absence of treatment. Although effective therapies for the initial management of HER2-positive metastatic breast cancer (MBC) exist, many patients will experience disease progression. Most second-line therapies are associated with either significant toxicities or limited improvements in overall survival (OS). Ado-trastuzumab emtansine is a HER2-positive directed antibody drug conjugate (ADC) approved in February 2013. In phase III clinical trials comparing the efficacy and safety of ado-trastuzumab emtansine with lapatinib-capecitabine or physician’s choice, ado-trastuzumab emtansine had a better tolerability profile and improved progression-free survival compared with lapatinib-capecitabine or physician’s choice and increased OS compared with lapatinib-capecitabine. Conclusion: Ado-trastuzumab emtansine is a novel ADC effective for HER2-positive MBC in patients previously treated with trastuzumab, lapatinib, and a taxane. Further studies will determine its use in the adjuvant and neoadjuvant setting and in combination with pertuzumab.

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2961-2968 ◽  
Author(s):  
Charlotte Fribbens ◽  
Ben O’Leary ◽  
Lucy Kilburn ◽  
Sarah Hrebien ◽  
Isaac Garcia-Murillas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Wild Type ◽  
Estrogen Receptor Positive ◽  
Esr1 Mutations ◽  
The Impact

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

scholarly journals Practice-Changing Interventions in the Systemic Management of Breast Cancer

2020 ◽  
Vol 18 (7.5) ◽  
pp. 941-944
Author(s):  
William J. Gradishar
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Breast Cancer Subtype ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Targeted Agents ◽  
Her2 Positive ◽  
Nccn Guidelines ◽  
Estrogen Receptor Positive ◽  
Treatment Paradigm

Systemic treatment for metastatic breast cancer now incorporates many targeted agents and a plethora of combinations specific to the breast cancer subtype. New to the treatment paradigm are fam-trastuzumab deruxtecan-nxki, and tucatinib for HER2-positive disease; the PI3K inhibitor alpelisib in combination with fulvestrant for estrogen receptor–positive and PIK3CA-mutated tumors; PARP inhibitors for patients with germline BRCA1/2 mutations; and the anti–PD-L1 agent atezolizumab in combination with albumin-bound paclitaxel for triple-negative disease with PD-L1 mutations in tumors. In addition, for estrogen receptor–positive disease, the role of CDK4/6 inhibitors increased substantially during the past year, as overall survival results have emerged. These targeted agents are greatly improving patient outcomes, and thus have all been incorporated into the NCCN Guidelines for Breast Cancer.

Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group phase III trial.

1997 ◽  
Vol 15 (7) ◽  
pp. 2494-2501 ◽  
Author(s):  
C A Russell ◽  
S J Green ◽  
J O'Sullivan ◽  
H E Hynes ◽  
G T Budd ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Metastatic Breast Cancer ◽  
Response Time ◽  
Treatment Failure ◽  
Metastatic Breast ◽  
Megestrol Acetate ◽  
Phase Iii ◽  
Time To Treatment Failure ◽  
Estrogen Receptor Positive

PURPOSE A phase III randomized trial was performed to determine whether combination hormonal therapy with aminoglutethimide (AG) and hydrocortisone (HC) plus megestrol acetate (MA) improved response rates, response duration, or increased survival over the sequential use of each hormone in women with estrogen receptor-positive metastatic breast cancer (MBC) who had maintained stable disease for at least 6 months or responded to tamoxifen. PATIENTS AND METHODS Two hundred eighty-eight postmenopausal women with progressive estrogen receptor-positive MBC were randomly selected to receive MA 40 mg four times daily (arm I), AG 250 mg four times daily with HC 40 mg daily in divided doses (arm II), versus the combination of MA plus AG given at the same dosages (arm III). Patients on arms I and II who progressed after an adequate trial were crossed over to the other treatment arm. RESULTS Two hundred thirty-five eligible patients were evaluated for response, time to treatment failure, and survival. Response was only reported for patients with measurable disease and was not statistically different among the three arms. There were two partial responses (PRs) on MA (6%), four complete responses (CRs) and six PRs on AG (24%), and eight PRs and three CRs on MA plus AG (23%) in 32, 42, and 48 measurable patients, respectively. Median times to treatment failure were also similar at 5, 4, and 7 months. Survival was also not statistically different among the three arms at 26, 27, and 26 months for arms I, II, and III, respectively. Toxicity was greater in the two AG arms with respect to fatigue, nausea and vomiting, and rash. CONCLUSION With the exception of toxicity, there is no response, time to treatment failure, or survival benefit for any one group when comparing MA, AG, or the combination at their stated doses in women with estrogen receptor-positive MBC who had previously responded to or stabilized with tamoxifen.

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