Outcomes with CDK4/6 inhibitors based on endocrine sensitivity in hormone receptor-positive metastatic breast cancer (HR+ MBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12526-e12526
Author(s):  
Amit L Jain ◽  
Janice Nhan Mullins ◽  
Kelsey Anne Poorman ◽  
Amina Chaudhry ◽  
Harsha Avinash Ranganath ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Endocrine Therapy ◽  
Real World ◽  
Endocrine Resistance ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Potential Biomarker ◽  
Esr1 Mutation

e12526 Background: PALOMA-3 results demonstrated that patients (pts) with sensitivity to previous endocrine therapy had a substantial benefit with Palbociclib compared to those with intrinsic endocrine resistance (Turner NC et al. NEJM 2018). ESR1 mutation has been associated with decreased response to endocrine therapy (Fribbens C et al. JCO 2016) and NSD3 amplification in breast cancer cells have been correlated with the overexpression of ESR1 (Irish JC et al. Mol Oncol 2016). Here we demonstrate a real-world response to CDK4/6i based on high-risk features and correlation to biomarkers of response. Methods: We retrospectively analyzed 115 HR+MBC pts at a single large community cancer center who received CDK4/6i + endocrine therapy and 40 matched controls treated with endocrine therapy and underwent NextGen Sequencing (NGS) profiling of 592 genes (Caris Life Sciences, Phoenix, AZ). The primary outcome was progression-free survival (PFS). Hazard ratios were calculated from Cox proportional hazards models built using the survival package[1] in R. Results: Among 115 pts in the CDK4/6i cohort, the median PFS for pts treated in the first-line (N=77) versus (vs.) second-line (N=38) was 9.7 and 4.6 months (mo) respectively (HR 2.04, p=0.001). Further, the median PFS in first-line cases who had a Disease-Free Survival (DFS) of >2 years (endocrine sensitive) (N=27) was 11.9 mo, and in pts with DFS < 2years (endocrine resistant) (N=24), it was 7.7 mo (HR 0.71, p= 0.397). Six pts with ESR1 mutations had worse PFS compared to ESR1 wild-type (N=40) when treated with CDK4/6i in 1st line, 6.4 vs. 18 mo (HR: 2.25, p=0.052) and 2nd line 2.5 (N=9) vs. 5.6 mo (N=17) HR: 2.09, p=0.1). NSD3 amplification was the only other genomic alteration showing significance as a negative predictor of PFS (first-line: 6.1 vs. 14.7 mo, HR: 2.40, p=0.04; second-line: 2.8 vs. 6.5 mo, HR: 3.61, p=0.06). NSD3 amplification appeared to have no significant effect in the control cohort 6.5 vs. 4.4 mo, (HR 1.29, p=0.63). Conclusions: In this real-world cohort, CDK 4/6 combination therapy benefits HR+ MBC patients in the first and second-line setting. ESR1 mutation is a predictor of worse outcome. NSD3 gene amplification is a potential biomarker of resistance to CDK4/6i combination therapy. (Therneau T (2015). A Package for Survival Analysis in S version 2.38, https://CRAN.R-project.org/package=survival).

scholarly journals Treatment of Metastatic Breast Cancer in a Real‐World Scenario: Is Progression‐Free Survival With First Line Predictive of Benefit From Second and Later Lines?

2015 ◽  
Vol 20 (7) ◽  
pp. 719-724 ◽  
Author(s):  
Marta Bonotto ◽  
Lorenzo Gerratana ◽  
Donatella Iacono ◽  
Alessandro Marco Minisini ◽  
Karim Rihawi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Bevacizumab (BEV) plus second-line taxane (TAX) or other chemotherapy (CT) for triple-negative breast cancer (TNBC): Subgroup analysis of RIBBON-2.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 290-290
Author(s):  
A. Brufsky ◽  
V. Valero ◽  
B. Tiangco ◽  
S. R. Dakhil ◽  
A. Brize ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Endpoint ◽  
Small Sample Size ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Small Sample ◽  
Second Line ◽  
First Line ◽  
Free Survival

290 Background: In three randomized trials in the first-line metastatic breast cancer (MBC) setting, combining BEV with CT significantly improved progression-free survival (PFS; primary endpoint) and objective response rate (ORR) vs. CT alone. BEV also showed a significant PFS benefit in the second-line MBC setting (RIBBON-2) when combined with TAX or other CT. We analyzed data from the subgroup of patients (pts) with TNBC in RIBBON-2. Methods: Eligible pts had MBC that had progressed on first-line CT without BEV. Second-line CT (TAX, gemcitabine, capecitabine, or vinorelbine) was chosen before 2:1 randomization to CT with either BEV (10 mg/kg q2w or 15 mg/kg q3w) or placebo (PLA). All pts could receive BEV at progression. The primary endpoint was PFS. Results: RIBBON-2 included 684 pts; 159 (23%) had TNBC and of these, 67 (42%) received TAX with BEV/PLA. Baseline characteristics were broadly similar in the two treatment arms. In an exploratory analysis of pts with TNBC, BEV + CT led to significantly improved PFS and ORR vs. CT alone, and a trend toward improved overall survival (OS). The magnitude of the effect was particularly pronounced in pts receiving TAX CT. Conclusions: Pts with TNBC derive significant ORR and PFS benefit from BEV combined with second-line CT. Despite the small sample size, there was a trend (HR 0.624; p = 0.0534) toward OS benefit in pts treated with BEV, especially with TAX CT. [Table: see text]

First-line endocrine therapy for advanced breast cancer. A real-world study at a Latin American university health institution

2020 ◽  
Vol 36 (7) ◽  
pp. 1195-1199
Author(s):  
Benjamin Walbaum ◽  
Francisco Acevedo ◽  
Lidia Medina ◽  
M. Loreto Bravo ◽  
Tomas Merino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Latin American ◽  
Real World ◽  
Advanced Breast ◽  
First Line ◽  
Health Institution ◽  
American University

scholarly journals Novel strategies to improve the endocrine therapy of breast cancer

2017 ◽  
Author(s):  
Aurelio Bartolome Castrellon
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptors ◽  
Endocrine Therapy ◽  
Targeted Therapies ◽  
Single Agent ◽  
Endocrine Resistance ◽  
Estrogen Therapy ◽  
Endocrine Treatment ◽  
Intrinsic Resistance ◽  
First Line

Endocrine therapy (ET) constitutes the usual first-line of therapy for patients in the treatment of metastatic hormone receptorpositive breast cancer. Unfortunately, not all patients respond to first-line endocrine treatment due to intrinsic resistance, while others may initially respond but eventually progress with secondary acquired resistance leading to disease progression. Mechanisms of resistance to anti-estrogen therapy include, loss of expression for estrogen or progesterone receptor, upregulation of epidermal receptor growth factor 2, increased receptor tyrosine kinase signaling, leading to activation of various intracellular pathways that are involved in signal transduction such as PI3K/AKT/mammalian target of rapamycin, and others. Growing understanding of the signal cascade of estrogen receptors and the signaling pathways that interact with estrogen receptors has revealed the complex role of these receptors in cell growth and proliferation, and on the mechanism in development of resistance. These insights have led to the development of targeted therapies that may prove to be effective options for the treatment of breast cancer and may overcome hormone therapy resistance. In this review we summarize some of the mechanisms of endocrine resistance, selected clinical trials of ET and targeted therapies, which might interfere with estrogen receptor pathways and might reduce or reverse resistance to traditional, sequential, single-agent ET.

scholarly journals Multicentric real world evidence with palbociclib in hormone positive HER2 negative metastatic breast cancer in Indian population

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chaturbhuj Agrawal ◽  
Pankaj Goyal ◽  
Amit Agarwal ◽  
Rupal Tripathi ◽  
Chandragouda Dodagoudar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Aromatase Inhibitors ◽  
Real World ◽  
Indian Population ◽  
Metastatic Breast ◽  
Second Line ◽  
First Line ◽  
Multicentric Study ◽  
Real World Evidence

AbstractThe combination of cyclin dependent kinase 4/6 inhibitors with endocrine therapy is the standard therapy in hormone receptor positive HER-2 negative metastatic breast cancer (HR+/HER2− MBC). Several randomized trials have shown the benefits of this combination, however, real world evidence in the Indian patients is warranted. The present study reports the largest real world multicentric data from Indian population on the use of Palbociclib in HR+/HER2− MBC. A multicentric study on the HR+/HER2− MBC patients who received palbociclib with hormonal agent (Aromatase inhibitors/Fulvestrant) between February 2017 and May 2020 was conducted. Clinical and demographic information and survival data was retrieved from the Hospital medical records. Among a total of 188 patients, 57% patients were premenopausal and 17% patients had bone only disease. Altogether, 115 (61%) patients received palbociclib with Aromatase inhibitors in the first line whereas 73 (39%) patients received it in the second line with Fulvestrant. The median follow up period with advanced disease was 13 months. The median progression free survival in the first line and second line was 20.2 months and 12 months, respectively (p-value < 0.0001). The objective response rate was 80% and 47.9% in first and second lines, respectively. Dose interruptions/ discontinuation were done in 14.9% and 2.7% patients in the first and second lines, respectively. In terms of toxicity, 10% patients had grade 3–4 adverse events. The present real world data of the use of palbociclib in Indian population suggests similar effectiveness to previously published real world evidences and has been adapted as the standard of care in the first and second line treatment of HR+/HER2− MBC.

scholarly journals TDM-1 efficacy in trastuzumab-pertuzumab pre-treated HER2 positive metastatic breast cancer patients: A meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13010-e13010
Author(s):  
Claudia Omarini ◽  
Federico Piacentini ◽  
Isabella Sperduti ◽  
Krisida Cerma ◽  
Monica Barbolini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real World ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Second Line ◽  
First Line ◽  
Her2 Positive ◽  
Real World Data ◽  
Line Setting

e13010 Background: Based on the results reported in Emilia trial population, current guidelines consider TDM-1 the standard second-line therapy for HER2 positive metastatic breast cancer (MBC) patients. Despite that, there are no prospective studies supporting the efficacy of TDM-1 following trastuzumab (T) + pertuzumab (P) and taxane first-line treatment. Currently, only real-world data have investigated this sequence with controversial results Methods: We performed a meta-analysis of the available real world data to determine the efficacy of TDM-1 after first-line TP in HER2 positive MBC patients. We used a random-effect model to find differences in the rate of 1-year progression free survival (PFS) between TP pre-treated population and the phase III Emilia trial (T pre-treated population). Results: Seven studies were eligible, in three of them data were from sub-group population analysis. The meta-analysis showed a combined 1-years PFS risk difference for TDM-1 efficacy after TP in second or more lines of -0.122, with lower and upper limits of -0.253 and 0.010, respectively (p=0.07) , with low heterogeneity among studies (I2 < 0.0001, p =0.836). Considering the four studies on TDM-1 in second-line setting, 1-years PFS risk was -0.034 (95% CI -0.207 – 0,139; p=0.701) (I2 < 0.0001, p =0.91). Conclusions: Results from the meta-analysis show that the efficacy of TDM-1 after TP double-block seems to be similar to the previously reported in Emilia trial. In the second line setting, available data are not mature enough to confirm TDM-1 efficacy in TP pre-treated population. Currently, TP pretreated patients should receive TDM-1 as indicated in the guidelines.

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