scholarly journals Bevacizumab and Breast Cancer: A Meta-Analysis of First-Line Phase III Studies and a Critical Reappraisal of Available Evidence

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
José R. Rossari ◽  
Otto Metzger-Filho ◽  
Marianne Paesmans ◽  
Kamal S. Saini ◽  
Alessandra Gennari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Statistical Estimates ◽  
Treatment Indications ◽  
Phase Iii Studies

Background. Randomized studies have shown different magnitude of bevacizumab benefit in the treatment of advanced breast cancer. Regulatory agencies have modified bevacizumab treatment indications across different regions. In this study, we perform a meta-analysis of phase III studies aiming to interrogate the magnitude of bevacizumab benefit for the treatment of first-line HER2-negative metastatic breast cancer (MBC).Methods. Data from studies E2100, AVADO and RIBBON-1 were used to calculate the benefit of bevacizumab in terms of tumor overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicities. Combined statistical estimates of hazard ratios (HR) and odds ratios were calculated using fixed-effects or random-effects models.Results. A total of 2,695 patients were evaluated. Combining bevacizumab with different chemotherapy backbones resulted in a 30% risk reduction of PFS events (HR = 0.70; 95% confidence interval [CI], 0.57–0.86) and increased ORR (odds ratio 1.81; 95% CI, 1.53–2.14). No OS benefit could be demonstrated (HR = 0.95; 95% CI, 0.85–1.06). Bevacizumab significantly increased the incidence of adverse events such as proteinuria, hypertension and cardiovascular events.Conclusions. Bevacizumab combined with chemotherapy in the first-line treatment of MBC significantly improved ORR and PFS, but also increased grade 3-4 toxicities. No significant OS advantage was observed.

Paclitaxel plus carboplatin versus paclitaxel plus epirubicin as first-line treatment for metastatic breast cancer: Efficacy and safety results of a randomized, phase III trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1087-1087
Author(s):  
Zhongsheng Tong ◽  
Shufen Li ◽  
Yehui Shi ◽  
Xu Wang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Free Survival ◽  
Significant Difference

1087 Background: Paclitaxel/carboplatin combinations are highly active in metastatic breast cancer (MBC). We conducted a randomized, phase III, non-inferiority trial comparing paclitaxel/carboplatin (TP) with paclitaxel/epirubicin (TE) as first-line therapy for MBC. Progression-free survival (PFS) was the primary efficacy endpoint. Secondary endpoints included response rate, overall survival, tolerability, and quality of life (QoL). Methods: From June 2009 to January 2015, 231 patients were randomly assigned, 115 of whom were randomized to TP and 116 to TE. Baseline characteristics were relatively well-balanced in the two treatments. Results: After a median follow-up of 29 months, no significant difference was observed between the two treatments in objective response rate (ORR) (38.3% vs. 39.7%, respectively). Both the progression-free survival (p=0.158) and overall survival (p=0.369) were very similar between the two treatments. Both regimens were well tolerated. The main toxicities were myelosuppression, gastrointestinal reactions, and alopecia. TP showed higher grades 3–4 alopecia and higher nausea (p<0.05). TE showed higher incidence of myelosuppression than TP (p<0.05) (Table). Those patients whose epirubicin cumulative dose was more than 1000 mg/m2 did not suffer worse cardiotoxicity. Conclusions: Our study suggests that TP arm is an effective therapeutic alternative for patients with MBC, especially in those previously exposed to epirubicin in the adjuvant setting. TP has some advantages, such as less cost and less side effects (myelosuppression and fatigue). Clinical trial information: NCT02207361. [Table: see text]

scholarly journals Taxanes Alone or in Combination With Anthracyclines As First-Line Therapy of Patients With Metastatic Breast Cancer

2008 ◽  
Vol 26 (12) ◽  
pp. 1980-1986 ◽  
Author(s):  
Martine J. Piccart-Gebhart ◽  
Tomasz Burzykowski ◽  
Marc Buyse ◽  
George Sledge ◽  
James Carmichael ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Meta Analysis ◽  
Single Agent ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Response Rates ◽  
First Line ◽  
First Line Therapy ◽  
Hazard Ratios

Purpose Taxanes (paclitaxel or docetaxel) have been sequenced or combined with anthracyclines (doxorubicin or epirubicin) for the first-line treatment of advanced breast cancer. This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival. Patients and Methods Individual patient data were collected on eight randomized combination trials comparing anthracyclines + taxanes (+ cyclophosphamide in one trial) with anthracyclines + cyclophosphamide (+ fluorouracil in four trials), and on three single-agent trials comparing taxanes with anthracyclines. Combination trials included 3,034 patients; single-agent trials included 919 patients. Results Median follow-up of living patients was 43 months, median survival was 19.3 months, and median PFS was 7.1 months. In single-agent trials, response rates were similar in the taxanes (38%) and in the anthracyclines (33%) arms (P = .08). The hazard ratios for taxanes compared with anthracyclines were 1.19 (95% CI, 1.04 to 1.36; P = .011) for PFS and 1.01 (95% CI, 0.88 to 1.16; P = .90) for survival. In combination trials, response rates were 57% (10% complete) in taxane-based combinations and 46% (6% complete) in control arms (P < .001). The hazard ratios for taxane-based combinations compared with control arms were 0.92 (95% CI, 0.85 to 0.99; P = .031) for PFS and 0.95 (95% CI, 0.88 to 1.03; P = .24) for survival. Conclusion Taxanes were significantly worse than single-agent anthracyclines in terms of PFS, but not in terms of response rates or survival. Taxane-based combinations were significantly better than anthracycline-based combinations in terms of response rates and PFS, but not in terms of survival.

scholarly journals Randomized Phase III Trial of Paclitaxel Once Per Week Compared With Nanoparticle Albumin-Bound Nab-Paclitaxel Once Per Week or Ixabepilone With Bevacizumab As First-Line Chemotherapy for Locally Recurrent or Metastatic Breast Cancer: CALGB 40502/NCCTG N063H (Alliance)

2015 ◽  
Vol 33 (21) ◽  
pp. 2361-2369 ◽  
Author(s):  
Hope S. Rugo ◽  
William T. Barry ◽  
Alvaro Moreno-Aspitia ◽  
Alan P. Lyss ◽  
Constance Cirrincione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Interim Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
First Line ◽  
Phase Iii Trial ◽  
First Line Therapy ◽  
Nonhematologic Toxicity

Purpose We compared nab-paclitaxel or ixabepilone once per week to paclitaxel with bevacizumab as first-line therapy for patients with advanced breast cancer (BC) to evaluate progression-free survival (PFS) for nab-paclitaxel or ixabepilone versus paclitaxel. Patients and Methods Eligible patients were age ≥ 18 years with chemotherapy-naive advanced BC. Patients were randomly assigned to bevacizumab with paclitaxel 90 mg/m2 (arm A), nab-paclitaxel 150 mg/m2 (arm B), or ixabepilone 16 mg/m2 (arm C), once per week for 3 of 4 weeks. Planned enrollment was 900 patients, which would give 88% power to detect a hazard ratio of 0.73. Results In all, 799 patients were enrolled, and 783 received treatment (97% received bevacizumab). Arm C was closed for futility at the first interim analysis (n = 241), and arm A (n = 267) and arm B (n = 275) were closed for futility at the second interim analysis. Median PFS for paclitaxel was 11 months, ixabepilone was inferior to paclitaxel (PFS, 7.4 months; hazard ratio, 1.59; 95% CI, 1.31 to 1.93; P < .001), and nab-paclitaxel was not superior to paclitaxel (PFS, 9.3 months; hazard ratio, 1.20; 95% CI, 1.00 to 1.45; P = .054). Results were concordant with overall survival; time to treatment failure was significantly shorter in both experimental arms v paclitaxel. Hematologic and nonhematologic toxicity, including peripheral neuropathy, was increased with nab-paclitaxel, with more frequent and earlier dose reductions. Conclusion In patients with chemotherapy-naive advanced BC, ixabepilone once per week was inferior to paclitaxel, and nab-paclitaxel was not superior with a trend toward inferiority. Toxicity was increased in the experimental arms, particularly for nab-paclitaxel. Paclitaxel once per week remains the preferred palliative chemotherapy in this setting.

Systematic review and meta-analysis of post-progression outcomes in ER+/HER2- metastatic breast cancer after treatment with endocrine therapy and CDK 4/6 inhibitors within randomized clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1059-1059
Author(s):  
Elisabetta Munzone ◽  
Eleonora Pagan ◽  
Vincenzo Bagnardi ◽  
Emilia Montagna ◽  
Giuseppe Cancello ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Fixed Effects ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Progression Free Survival

1059 Background: CDK4/6 inhibitors combined with endocrine therapy (ET) deeply transformed the treatment landscape of HR+/HER2− advanced breast cancer. After progression with the combination, there are no established guidelines for an optimal sequencing of the various therapeutic options. Data from randomized clinical trials (RCT) suggest that subsequent progression free survival (PFS2) was not compromised by the use of these drugs and time to subsequent chemotherapy (TTC) may be delayed. Therefore, we performed a meta-analysis to evaluate the benefit of such treatments on PFS2 and on delaying the TTC. Methods: We conducted a systematic literature search using PubMed to select all available randomized clinical trials of CDK4/6-inhibitors and ET reporting PFS2 or TTC data in first- or second-line therapy of HR+/HER2- pre- or postmenopausal metastatic breast cancer. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled hazard ratios (HR) for PFS2 and TTC with 95% confidence intervals (CI) using fixed-effects models. The pooled HRs for PFS and OS were also calculated. I2 was used to quantify heterogeneity between studies’ results. Results: Seven studies (PALOMA 1-2-3, MONALEESA 3-7, MONARCH 2-3) were included in our analyses (n = 3912 patients). A clear PFS2 benefit was observed in patients who received CDK 4/6 inhibitors + ET (pooled HR = 0.67, 95% CI = 0.61 to 0.74, I2 = 0.0%) and also a delay in subsequent TTC (pooled HR = 0.63, 95% CI = 0.58 to 0.70, I2 = 0.0%). As previously reported, the benefit in terms of PFS (pooled HR = 0.54, 95% CI = 0.50 to 0.59, I2= 0%) and OS (pooled HR = 0.77, 95% CI = 0.68 to 0.86, I2= 0%) was also confirmed. Conclusions: CDK4/6-inhibitors plus ET compared with ET alone improve PFS2, and TTC. The delay of chemotherapy can spare the patients toxicities, potentially improving the quality of life. Thus, the observed benefit in PFS2 may postpone the onset of endocrine resistance and may offer an additional therapeutic advantage in this setting.

Duration of Chemotherapy for Metastatic Breast Cancer: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

2011 ◽  
Vol 29 (16) ◽  
pp. 2144-2149 ◽  
Author(s):  
Alessandra Gennari ◽  
Martin Stockler ◽  
Matteo Puntoni ◽  
Mariapia Sormani ◽  
Oriana Nanni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Published Data ◽  
First Line ◽  
Line Chemotherapy

Purpose To evaluate the effect of different first-line chemotherapy durations in patients with metastatic breast cancer (MBC) on overall survival (OS) and progression-free survival (PFS). Methods We searched literature databases to identify randomized controlled trials that compared different chemotherapy durations in the first-line treatment of MBC. Only trials with unconfounded comparisons of additional cycles of chemotherapy were included. The main outcome measures for this analysis were OS and PFS. Published data from retrieved studies were analyzed according to standard meta-analytic techniques. Results We found 11 randomized clinical trials including 2,269 patients. Longer first-line chemotherapy duration resulted into a significantly improved OS (hazard ratio [HR], 0.91; 95% CI, 0.84 to 0.99; P = .046) and PFS (HR, 0.64; 95% CI, 0.55 to 0.76; P < .001). There were no differences in effects on either OS or PFS between subgroups defined by time of random assignment, study design, number of chemotherapy cycles in the control arm or concomitant endocrine therapy. Conclusion Longer first-line chemotherapy duration is associated with marginally longer OS and a substantially longer PFS.

scholarly journals Phase II study of metronomic treatment with daily oral vinorelbine as first-line chemotherapy in patients with advanced/metastatic HR+/HER2− breast cancer resistant to endocrine therapy: VinoMetro—AGO-B-046

2021 ◽  
Author(s):  
Slavomir Krajnak ◽  
Thomas Decker ◽  
Lukas Schollenberger ◽  
Christian Rosé ◽  
Christian Ruckes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Open Label ◽  
Oral Vinorelbine ◽  
Her2 Breast Cancer ◽  
Line Chemotherapy

Abstract Purpose Metronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. Methods VinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2− MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. Results Between January 2017 and April 2019, nine patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1–55.0), p = 0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3–12.7). Grade 3–4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia. Conclusion VinoMetro (AGO-B-046) was closed early after nine patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2− MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population. Trial registration number and date of registration ClinicalTrials.gov Identifier: NCT03007992; December 15, 2016.

The cost-effectiveness of atezolizumab in first-line for metastatic triple negative breast cancer is heavily linked to PD-L1 level

2021 ◽  
pp. 107815522110194
Author(s):  
Jacopo Giuliani ◽  
Beatrice Mantoan ◽  
Andrea Bonetti
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Controlled Trial ◽  
Metastatic Breast ◽  
Cost Effective ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Pivotal Phase ◽  
First Line Treatment

The present analysis was conducted to assess the pharmacological costs of atezolizumab as first-line treatment in triple negative metastatic breast cancer (mBC). Pivotal phase III randomized controlled trial (RCT) was considered. Nine hundred and two patients were included. Differences in costs between the 2 arms (atezolizumab plus nabpaclitaxel versus placebo plus nab-paclitaxel) was 17 398 €, with a cost of 7564 €per month of OS-gain in the overall population and 2485 €per month of OS-gain in PD-L1-positive (≥1) population. Combining pharmacological costs of drugs with the measure of efficacy represented by the OS, atezolizumab could be considered cost-effective in first-line treatment for triple-negative mBC only in PD-L1-positive population, but a reduction of costs is mandatory.

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