Polymorphisms interaction to predict bevacizumab (BV) efficacy in metastatic breast cancer (MBC) patients (pts): An exploratory retrospective analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1086-1086
Author(s):  
Luigi Coltelli ◽  
Andrea Fontana ◽  
Guido Bocci ◽  
Andrea Camerini ◽  
Antonella Ferro ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Genetic Interaction ◽  
Metastatic Breast ◽  
Genetic Profile ◽  
Nucleotide Polymorphisms ◽  
Non Profit ◽  
Hormone Receptor Positive ◽  
Ecog Ps

1086 Background: Previous retrospective studies have attempted to identify a possible role of VEGF single nucleotide polymorphisms (SNPs) to predict BV efficacy in terms of OS and PFS in MBC pts with conflicting results (Schneider 2008, Grimaldi 2011, Lambrechts 2011). Methods: On the basis of these preliminary data, we decided to assess in a MBC population if different VEGF, VEGFR-2, IL-8, IL-6, HIF-1alfa, EPAS-1 and TSP-1 genotypes could predict first line BV + paclitaxel (P) response in terms both of OS and PFS. Analyses were performed on germline DNA obtained from blood samples. Fourteen polymorphisms were investigated by real-time PCR technique. Both single and combinations of SNPs were investigated. The multifactor dimensionality reduction (MDR) methodology was applied to identify a genetic interaction profile for PFS ( http://sourgeforge.net/projects/mdr/ ). Results: 102 pts have been enrolled from 8 Oncology Units. Main pts characteristics are: median age 59 years (range 32-81), ECOG-PS 0/1 in 78%/22%, hormone receptor positive 83%, previous adjuvant chemotherapy 68%, disease free interval (DFI) < 12 months 27%. After a median follow up of 17.4 months (1.9-54.7), mPFS was 11.6 months (95% CI: 10.6-12.6) and mOS was 32.4 months (95% CI: 25.9-38.9). None of SNPs were individually associated with PFS. Conversely, a genetic interaction profile consisting of VEGFR-2 rs11133360 and IL-8 rs4073 was significantly associated with PFS. mPFS was 14 months (95% CI: 11.7-16.3) and 10.9 months (95% CI: 9.3-12.4) for the favorable and unfavorable genetic profile, respectively (HR=0.63, 95% CI: 0.4-0-99, p= 0.046). Furthermore, at the multivariate analysis hormone receptor positive (HR=0.22, 95% CI: 0.12-0-41, p<0.0001), DFI >12 months (HR= 0.4, 95% CI: 0.2-0.82, p= 0.011) and BV maintenance (HR=0.63, 95% CI: 0.25.0.71, p=0.001) were significantly associated with a better PFS. Conclusions: Genetic interaction between VEGFR-2 rs11133360 and IL-8 rs4073 polymorphisms could predict BV response in terms of PFS. With a longer follow-up correlations with OS will be investigated. Prospective study is planned. Study supported by the non-profit foundation F.A.R.O.

Final analysis of the PROMISE-GIM6 phase III trial assessing GnRH agonist use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 516-516
Author(s):  
Matteo Lambertini ◽  
Luca Boni ◽  
Andrea Michelotti ◽  
Emanuela Magnolfi ◽  
Alessio Aligi Cogoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Ovarian Function ◽  
Final Analysis ◽  
Post Treatment ◽  
Phase Iii ◽  
Hormone Receptor Positive ◽  
Premenopausal Patients

516 Background: Current guidelines recommend GnRH agonist (GnRHa) use during chemotherapy (CT) as a strategy to reduce the risk of premature ovarian insufficiency (POI) in premenopausal patients with early breast cancer (EBC). However, no long-term safety data are available raising some concerns on concurrent use of GnRHa during CT in patients with hormone receptor-positive disease. In addition, there is no evidence on the protective role of this strategy in patients with germline BRCA mutations ( mBRCA). Here, we report the final analysis of the PROMISE-GIM6 phase III randomized study, the largest trial addressing the role of GnRHa use during CT in premenopausal EBC patients (Del Mastro et al, JAMA 2011 & Lambertini et al, JAMA 2015). Methods: From October 2003 to January 2008, 281 premenopausal patients aged 18 to 45 years with stage I-III EBC candidates for (neo)adjuvant CT were randomized to receive CT alone or combined with the GnRHa triptorelin. Primary endpoint was incidence of CT-induced POI (defined as amenorrhea and post-menopausal FSH/estradiol levels 1 year following CT). This final analysis reports on post-treatment pregnancies, disease-free survival (DFS) and overall survival (OS). An exploratory descriptive analysis in mBRCA patients is also reported. (ClinicalTrial.gov: NCT00311636) Results: Of the 281 randomized patients (CT+GnRHa arm = 148; CT alone arm = 133), 80% had hormone receptor-positive disease. At the time of this final analysis, 38 (13.5%) patients were lost to follow-up. Median follow-up was 12.4 years (IQR: 11.3-13.2 years). In the CT+GnRHa and CT alone arms, respectively, 9 (10-year cumulative incidence of pregnancy 6.5%, 95% CI 3.5%-12.3%) and 4 (10-year cumulative incidence of pregnancy 3.2%, 95% CI 1.2%-8.3%) patients had a post-treatment pregnancy (HR 2.14, 95% CI 0.66-6.92). No differences in 10-year DFS (72.4% in CT+GnRHa arm vs. 71.2% in CT alone arm: HR 1.16, 95% CI 0.76-1.77) nor in 10-year OS (82.0% in CT+GnRHa arm vs. 85.9% in CT alone arm: HR 1.17, 95% CI 0.67-2.03) were observed. There was no interaction between treatment effect and hormone receptor status. In patients with hormone receptor-positive disease, HR was 1.02 (95% CI 0.63-1.63) for DFS and 1.12 (95% CI 0.59-2.11) for OS. Out of 43 patients tested for BRCA, overall incidence of POI, irrespective of treatment arm, was 20% in mBRCA patients (n = 10) and 12% in patients without mBRCA (n = 33). In mBRCA patients, incidence of POI was 0% and 33% in the CT+GnRHa and CT alone arms, respectively. One post-treatment pregnancy was described in a patient with mBRCA1 in the CT alone arm. Conclusions: The final analysis of the PROMISE-GIM6 trial at a median follow-up of 12.4 years provides reassuring evidence on the safety of GnRHa use during CT as a strategy to preserve ovarian function in premenopausal patients with hormone receptor-positive EBC. Clinical trial information: NCT00311636.

scholarly journals Role of palbociclib in the treatment of hormone receptor-positive HER2-negative metastatic breast cancer. Generalizing results of randomized trials and real clinical practice

2019 ◽  
pp. 56-62
Author(s):  
L. G. Zhukova ◽  
E. I. Khatkova ◽  
P. S. Feoklistova ◽  
K. S. Grechukhina ◽  
S. A. Smolin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Hormone Receptor ◽  
Randomized Trials ◽  
Metastatic Breast ◽  
Second Line Therapy ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer ◽  
Real Clinical Practice

Palbociclib is the first-in-class drug of CDK 4/6 inhibitors group. The use of palbociclib in combination with endocrinotherapy (ET) opens up new possibilities for the treatment of metastatic hormone receptor-positive (HRP+) HER2-negative (HER2-) breast cancer (mBC). Palbociclib has gained world attention and is included in all clinical guidelines, both international and domestic, as a new standard of first- and second-line therapy of HRP+ HER2- mBC. The article presents the updated results of PALOMA-2 and PALOMA-3 studies and the results of use of palbociclib in combination with ET in real clinical practice.

scholarly journals Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer

2015 ◽  
Vol 33 (21) ◽  
pp. 2353-2360 ◽  
Author(s):  
Joseph A. Sparano ◽  
Fengmin Zhao ◽  
Silvana Martino ◽  
Jennifer A. Ligibel ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Operable Breast Cancer ◽  
Weekly Paclitaxel ◽  
Black Race ◽  
Hormone Receptor Positive

Purpose To determine long-term outcomes in a clinical trial evaluating the role of taxane type and schedule in operable breast cancer and evaluate the impact of obesity and black race on outcome. Patients and Methods A total of 4,954 eligible women with stage II to III breast cancer treated with four cycles of doxorubicin plus cyclophosphamide were randomly assigned to receive paclitaxel or docetaxel every 3 weeks for four doses or weekly for 12 doses using a 2 × 2 factorial design. The primary end point was disease-free survival (DFS). Results are expressed as hazard ratios (HRs) from Cox proportional hazards models. All P values are two sided. Results When compared with the standard every-3-week paclitaxel arm, after a median follow-up of 12.1 years, DFS significantly improved and overall survival (OS) marginally improved only for the weekly paclitaxel (HR, 0.84; P = .011 and HR, 0.87; P = .09, respectively) and every-3-week docetaxel arms (HR, 0.79; P = .001 and HR, 0.86; P = .054, respectively). Weekly paclitaxel improved DFS and OS (HR, 0.69; P = .010 and HR, 0.69; P = .019, respectively) in triple-negative breast cancer. For hormone receptor–positive, human epidermal growth factor receptor 2–nonoverexpressing disease, no experimental arm improved OS, and black race and obesity were associated with increased risk of breast cancer recurrence and death. Conclusion Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease. Further research is required to understand why obesity and race influence clinical outcome in hormone receptor–positive disease.

Real-world evidence evaluating continuation of CDK4/6 inhibitors beyond first progression in hormone receptor-positive (HR+) metastatic breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12538-e12538 ◽  
Author(s):  
Akaolisa Samuel Eziokwu ◽  
Leticia Varella ◽  
Megan Lynn Kruse ◽  
Xuefei Jia ◽  
Halle C. F. Moore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Disease Progression ◽  
Endocrine Therapy ◽  
Real World ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Hormone Receptor Positive ◽  
Real World Evidence

e12538 Background: CDK inhibitors (CDKi), in combination with aromatase inhibitors (AI), are approved for the treatment of hormone receptor positive (HR+) Her2 negative metastatic breast cancer (MBC). The effectiveness of continuing CDKi beyond first disease progression is not known. This study evaluated real world evidence and assessed the impact of continuation of CDKi beyond first disease progression in combination with endocrine therapy. Methods: This is a retrospective, single institution review of HR+ MBC patients treated with CDKi from 2015-2018 who continued CDKi after initial progression. The primary outcome was progression-free survival (PFS) beyond first disease progression, as assessed by the clinician based on radiological and/or clinical criteria. Overall survival (OS) – defined as date of initial CDKi treatment to date of death or last follow up – was a secondary outcome. Results: 30 women with HR+/HER2- MBC, median age 47.5 years (range: 31 – 81), sequentially continued on CDKi beyond first progression were identified from a database of patients treated with Palbociclib. Median and average follow up times on CDKi were 27.18 and 24.53 months, respectively. Initial endocrine/CDKi regimen received included: palbociclib (PA)/letrozole (LTZ) [67%], PA/fulvestrant (FULV) [23%], and PA/other AI [10%]. Prescribed combinations beyond 1st progression were: PA/FULV [56.7%], PA/LTZ [16.7%], and PA/other AI [20%], abemaciclib plus LTZ or FULV [6%]. As of 1/31/2019, 25 patients (83.3%) were still alive, and 19 (63%) had undergone a second progression on CDKi. The estimated median PFS for the entire duration while on CDKi was 23.5 months (95% CI 12.8 – 27.8), of which 11.8 months (95% CI 5.34 – 13.13) was the median PFS beyond first progression. The estimated median OS was 45.4 months. Conclusions: Among a small cohort of HR+ MBC patients, in a non-clinical trial setting, continuation of palbociclib plus endocrine therapy beyond first progression was associated with a median PFS of approximately 11 months. Formal clinical evaluation of continuation of CDK inhibitor plus endocrine therapy beyond first progression is warranted.

Letrozole (L) with bevacizumab (B) is feasible in patients (pts) with hormone receptor-positive metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3050-3050 ◽  
Author(s):  
T. A. Traina ◽  
H. Rugo ◽  
J. Caravelli ◽  
B. Yeh ◽  
K. Panageas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Hot Flashes ◽  
Metastatic Breast ◽  
First Line ◽  
Prior Therapy ◽  
Hormone Receptor Positive ◽  
Secondary Endpoints ◽  
Breast Cancer Growth ◽  
Ecog Ps

3050 Background: Bevacizumab added to chemotherapy (CRx) prolongs PFS in pts with MBC. Data suggest that estrogen (E2) modulates VEGF-induced angiogenesis in physiologic and pathologic conditions. E2-induced VEGF expression may promote breast cancer growth therefore combination therapy with an aromatase inhibitor (AI) and an antibody to VEGF may be more effective than either agent alone. We performed a feasibility study testing B with L for the treatment (tx) of hormone receptor-positive MBC. Methods: Eligible pts have MBC and are candidates for AI therapy. Prior non-steroidal AI (NSAI) use without progression is permitted. Premenopausal pts undergo ovarian suppression/oophorectomy prior to tx. Therapy consists of L (2.5 mg daily) and B (15 mg/kg IV q3 weeks). The primary endpoint is frequency of Grade (Gr) 4 toxicity. Secondary endpoints include response rate, stable disease (SD) ≥ 6 mo and time to tumor progression. Using a two-stage design, 19 pts were accrued. Because <3 pts had Gr 4 toxicity, the 2nd stage is now enrolling an additional 23 pts. If <5 of the 42 pts have Gr 4 toxicity, the regimen will be considered feasible. Results: Thirty two pts are currently accrued and 28 are now evaluable. Medians: Age 49.5 yrs (32–77) and ECOG PS 0 (0–1). Sites of MBC: bone only 11/28, visceral 16/28, chest wall/soft tissue/lymph nodes 11/28. All are ER and/or PR (+); none are HER2 (+). Prior therapy: adjuvant CRx 20; adjuvant tamoxifen 14. Twenty five pts received an NSAI as first-line tx of MBC, starting a median of 23 wks (1–213) before B. Three pts received first-line tamoxifen; one pt had prior CRx for MBC. After a median of 8 cycles (1–20), tx-related toxicities: Gr 2: hypertension (HTN) 4, headache (HA) 4, proteinuria 3, fatigue 6, joint pain 5, hot flashes 1, epistaxis 1; Gr 3: HTN 5, HA 1, proteinuria 1. There has been no tx-related Gr 4/5 toxicity. Tx-related withdrawals: HTN 1 and headache 1. Twenty five pts are evaluable for response: PR 2, SD ≥ 6 mo 13, SD 4, progression 6. Conclusions: Combination L and B is well tolerated and will be studied in a randomized CALGB trial. Circulating endothelial and tumor cell data is reported separately. Supported in part by Genentech and Novartis. [Table: see text]

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