Dataset Information

Early and late outcomes of bevacizumab plus chemotherapy versus chemotherapy alone as a neoadjuvant treatment in HER2-negative nonmetastatic breast cancer: a meta-analysis of randomized controlled trials.

ABSTRACT:

Purpose

To better clarify the efficacy of neoadjuvant bevacizumab plus chemotherapy (BEV + CT) vs chemotherapy (CT) alone in the treatment of HER2-negative nonmetastatic breast cancer.

Methods

PubMed, Embase, Web of Science, and Cochrane Library databases were searched for relevant articles published from January 1, 2000 to July 31, 2018. Review Manager software version 5.3 was used to perform this meta-analysis.

Results

Six randomized controlled trials matched the selection criteria, yielding a total of 4,354 patients with early outcomes and 3,777 patients with late outcomes. Pooled pathological complete response (pCR) and 5-year disease-free survival (DFS) rates were higher for the neoadjuvant BEV + CT group (OR =1.37 [1.19, 1.58]; P<0.001 and HR =0.84 [0.72, 0.98]; P=0.020, respectively), but 5-year overall survival (OS) rate showed no significant difference (HR =0.79 [0.55, 1.11]; P=0.180). Subgroup analysis showed that the pCR rate was significantly higher in both patients with hormone receptor (HR)-positive breast cancer (OR =1.30 [1.01, 1.66]; P=0.040) and those with HR-negative breast cancer (OR =1.52 [1.25, 1.83]; P<0.001) in BEV + CT group.

Conclusion

Compared with CT alone, neoadjuvant BEV + CT significantly improved the 5-year DFS rate of HER2-negative breast cancer patients, but showed no benefit in terms of 5-year OS rate.

SUBMITTER: Wei J

PROVIDER: S-EPMC6296181 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Early and late outcomes of bevacizumab plus chemotherapy versus chemotherapy alone as a neoadjuvant treatment in HER2-negative nonmetastatic breast cancer: a meta-analysis of randomized controlled trials.

Wei Jinli J Luo Yulin Y Fu Deyuan D

OncoTargets and therapy 20181212

<h4>Purpose</h4>To better clarify the efficacy of neoadjuvant bevacizumab plus chemotherapy (BEV + CT) vs chemotherapy (CT) alone in the treatment of HER2-negative nonmetastatic breast cancer.<h4>Methods</h4>PubMed, Embase, Web of Science, and Cochrane Library databases were searched for relevant articles published from January 1, 2000 to July 31, 2018. Review Manager software version 5.3 was used to perform this meta-analysis.<h4>Results</h4>Six randomized controlled trials matched the selectio ...[more]

PMID: 30588017

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Project description:PurposeResults from previous randomised controlled trials (RCTs) investigating whether the addition of bevacizumab to neoadjuvant chemotherapy (NAC) could statistically significantly increase the pathological complete response (pCR) and to identify which subgroup would benefit most from such regimens have produced conflicting results. This meta-analysis was designed to assess the efficacy and safety of bevacizumab plus chemotherapy compared with chemotherapy alone in the neoadjuvant setting.MethodsA literature search of MEDLINE, EMBASE, Web of Science, and the Cochrane library was performed to identify eligible studies. The primary endpoint of interest was pCR. The secondary endpoints were clinical complete rate (cCR), surgery rate, breast-conserving surgery (BCS) rate, and toxicity. The meta-analysis was performed using Review Manager software version 5.3.ResultsNine RCTs matched the selection criteria, yielding a total of 4967 patients (bevacizumab plus chemotherapy: 50.1%, chemotherapy alone: 49.9%). The results of this meta-analysis demonstrated that the addition of bevacizumab to NAC significantly increased the pCR rate (odds ratio [OR] = 1.34 [1.18-1.54]; P < 0.0001) compared with chemotherapy alone. Subgroup analysis showed that the effect of bevacizumab was more pronounced in patients with HER2-negative cancer (OR = 1.34 [1.17-1.54]; P < 0.0001) compared with HER2-positive cancer (OR = 1.69 [0.90-3.20]; P = 0.11). Similarly, in patients with HER2-negative cancer, the effect of bevacizumab was also more pronounced in patients with HR-negative cancer (OR = 1.38 [1.09-1.74]; P = 0.007) compared with HR-positive cancer (OR = 1.36 [0.78-2.35]; P = 0.27). No significant differences were observed between the groups with respect to cCR, surgery rate, or BCS rate. Additionally bevacizumab was associated with a higher incidence of neutropenia, febrile neutropenia, and hand-foot syndrome.ConclusionsHigher proportions of patients achieved pCR when bevacizumab was added to NAC compared with when they received chemotherapy alone; acceptable toxicities were also found. Subgroup analysis demonstrated that patients with histologically confirmed HER2-negative and HR-negative breast cancer benefited the most.

Project description:PurposeZoledronic acid (ZOL) is a nitrogen-containing bisphosphonate that induces osteoclast apoptosis and inhibits bone resorption by inhibiting the mevalonate pathway. Its benefit for the prevention of skeletal complications due to bone metastases has been established. However, the antitumor efficacy of ZOL, although suggested by multiple preclinical and clinical studies, has not yet been clinically proven. We performed the present randomized Phase 2 trial to investigate the antitumor effect of ZOL with chemotherapy (CT).MethodsAsian patients with HER2-negative invasive breast cancer were randomly assigned to either the CT or CT+ZOL (CTZ) group. One hundred and eighty-eight patients were randomized to either the CT group (n = 95) or the CTZ group (n = 93) from March 2010 to April 2012, and 180 patients were assessed. All patients received four cycles of FEC100 (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2), followed by 12 cycles of paclitaxel at 80 mg/m2 weekly. ZOL (4 mg) was administered three to four times weekly for 7 weeks to the patients in the CTZ group. The primary endpoint was the pathological complete response (pCR) rate, which was defined as no invasive cancer in the breast tissue specimen. Safety was assessed in all patients who received at least one dose of the study drug.ResultsThis randomized controlled trial indicated that the rates of pCR in CTZ group (14.8%) was doubled to CT group (7.7%), respectively (one-sided chi-square test, p = 0.068), though the additional efficacy of zoledronic acid was not demonstrated statistically. The pCR rate in postmenopausal patients was 18.4% and 5.1% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.071), and that in patients with triple-negative breast cancer was 35.3% and 11.8% in the CTZ and CT groups, respectively (one-sided Fisher's exact test, p = 0.112). Thus the addition of ZOL to neoadjuvant CT has potential anticancer benefits in postmenopausal patients and patients with triple-negative breast cancer. Further investigation is warranted.Trial registrationUniversity Hospital Medical Information Network. UMIN000003261.

Project description:Importance:Combining conventional chemotherapy with targeted therapy has been proposed to improve the pathologic complete response (pCR) rate in patients with inflammatory breast cancer (IBC). Epidermal growth factor receptor (EGFR) expression is an independent predictor of low overall survival in patients with IBC. Objective:To evaluate the safety and efficacy of the anti-EGFR antibody panitumumab plus neoadjuvant chemotherapy in patients with primary human epidermal growth factor receptor 2 (HER2)-negative IBC. Design, Setting, and Participants:Women with primary HER2-negative IBC were enrolled from 2010 to 2015 and received panitumumab plus neoadjuvant chemotherapy. Median follow-up time was 19.3 months. Tumor tissues collected before and after the first dose of panitumumab were subjected to immunohistochemical staining and RNA sequencing analysis to identify biomarkers predictive of pCR. Intervention:Patients received 1 dose of panitumumab (2.5 mg/kg) followed by 4 cycles of panitumumab (2.5 mg/kg), nab-paclitaxel (100 mg/m2), and carboplatin weekly and then 4 cycles of fluorouracil (500 mg/m2), epirubicin (100 mg/m2), and cyclophosphamide (500 mg/m2) every 3 weeks. Main Outcomes and Measures:The primary end point was pCR rate; the secondary end point was safety. The exploratory objective was to identify biomarkers predictive of pCR. Results:Forty-seven patients were accrued; 7 were ineligible. The 40 enrolled women had a median age of 57 (range, 23-68) years; 29 (72%) were postmenopausal. Three patients did not complete therapy because of toxic effects (n?=?2) or distant metastasis (n?=?1). Nineteen patients had triple-negative and 21 had hormone receptor-positive IBC. The pCR and pCR rates were overall, 11 of 40 (28%; 95% CI, 15%-44%); triple-negative IBC, 8 of 19 (42%; 95% CI, 20%-66%); and hormone receptor-positive/HER2-negative IBC, 3 of 21 (14%; 95% CI, 3%-36%). During treatment with panitumumab, nab-paclitaxel, and carboplatin, 10 patients were hospitalized for treatment-related toxic effects, including 5 with neutropenia-related events. There were no treatment-related deaths. The most frequent nonhematologic adverse event was skin rash. Several potential predictors of pCR were identified, including pEGFR expression and COX-2 expression. Conclusions and Relevance:This combination of panitumumab and chemotherapy showed the highest pCR rate ever reported in triple-negative IBC. A randomized phase 2 study is ongoing to determine the role of panitumumab in patients with triple-negative IBC and to further validate predictive biomarkers. Trial Registration:ClinicalTrials.gov Identifier: NCT01036087.

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Dataset Information

Early and late outcomes of bevacizumab plus chemotherapy versus chemotherapy alone as a neoadjuvant treatment in HER2-negative nonmetastatic breast cancer: a meta-analysis of randomized controlled trials.

Purpose

Methods

Results

Conclusion

Publications

Early and late outcomes of bevacizumab plus chemotherapy versus chemotherapy alone as a neoadjuvant treatment in HER2-negative nonmetastatic breast cancer: a meta-analysis of randomized controlled trials.

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