Is nab-paclitaxel better than conventional taxanes as neoadjuvant therapy for breast cancer? A meta-analysis

Objective This study compared the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with conventional taxanes as neoadjuvant chemotherapy for breast cancer. Methods We searched the literature using PubMed, the Cochrane Library, and Web of Science from their inception to December 15, 2019 based on predetermined inclusion and exclusion criteria. The relevant studies compared pathologic complete response (pCR) and adverse event rates. Results The meta-analysis included five studies and 2335 patients. Compared with conventional taxanes, neoadjuvant chemotherapy with nab-paclitaxel was associated with a higher pCR rate (odds ratio [OR] = 1.39, 95% confidence interval [CI] = 1.16–1.67), especially among patients with triple-negative breast cancer or Ki67 indices of >20%. Pooled outcomes also revealed better event-free survival in the nab-paclitaxel group (hazard ratio = 0.69, 95% CI = 0.57–0.85). However, all-grade (OR = 2.17, 95% CI = 1.38–3.40) and grade ≥3 peripheral sensory neuropathy (OR = 3.92, 95% CI = 2.44–6.28) were more frequent in the nab-paclitaxel group. Conclusions This meta-analysis implied that nab-paclitaxel more effectively improved pCR than conventional taxanes. Nab-paclitaxel may have greater benefits in patients with triple-negative breast cancer. However, additional attention is required for the early diagnosis and management of peripheral sensory neuropathy.

Download Full-text

Neoadjuvant chemotherapy regimens for triple-negative breast cancer: Insights from network meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12635 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12635-e12635

Author(s):

Hirotaka Miyashita ◽

Christina Cruz ◽

Stephen C. Malamud

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Meta Analysis ◽

Cochrane Library ◽

Gastrointestinal Complications ◽

Therapy Regimen ◽

Neoadjuvant Systemic Therapy ◽

Grade 3

e12635 Background: The best regimen for neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) is unknown. Recent studies have shown promising data that adding carboplatin improves the rate of pathological complete response (pCR) in TNBC). Therefore, we performed a network meta-analysis to define the overall most effective neoadjuvant systemic therapy for TNBC. Methods: We searched MEDLINE, Cochrane Library, and EMBASE from inception to December 2019 for studies comparing the efficacy of different neoadjuvant regimens in patients with TNBC. We performed a network meta-analysis comparing the regimens in the selected studies using the random-effects model. We focused on anthracycline (A), bevacizumab (B), everolimus (E), and platinum salts (Pl) because these are the medications commonly added to taxane based regimens. All studies contained a taxane regimen. We analyzed the rate of pCR (ypT0/is, N0) and the incidence of grade 3-4 neutropenia, thrombocytopenia, nausea/vomiting, and diarrhea. Results: We identified a total of 13 randomized control trials for this analysis. We compared eight different classes of regimens. We found that regimens containing Pl were significantly superior to Pl non-containing regimens for the rate of pCR. (risk ratio (RR) for pCR [95% confidence interval (CI)]: 1.66 [1.19-2.31], 1.37 [1.14-1.64], and 1.36 [1.14-1.62] for no medications of special interest vs Pl, A vs A+Pl, and A+B vs A+B+Pl, respectively). Regimens containing B were associated with a significantly better rate of pCR. (RR for pCR [95% CI]: 1.24 [1.06-1.46] and 1.23 [1.01-1.51] for A vs A+B and A+Pl vs A+B+Pl, respectively) In contrast, adding A into the regimen did not improve the rate of pCR. In the safety analysis, regimens containing Pl were associated with a significantly higher incidence of grade 3-4 neutropenia and thrombocytopenia. Regimens containing B showed a higher incidence of grade 3-4 nausea/vomiting, and diarrhea. Conclusions: For TNBC, adding Pl or B into the neoadjuvant therapy regimen brings about a higher pCR rate, though they are associated with an increase in hematologic or gastrointestinal complications. The benefit of adding A to the neoadjuvant chemotherapy regimen for TNBC is not apparent.

Download Full-text

The Clinical Value of Chemotherapy Combined With Capecitabine in Triple-Negative Breast Cancer—A Meta-Analysis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.771839 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zilin Zhang ◽

Kai Ma ◽

Jing Li ◽

Yeneng Guan ◽

Chaobo Yang ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Meta Analysis ◽

Safety Analysis ◽

Cochrane Library ◽

Control Group ◽

Annual Conference ◽

Hand Foot Syndrome

Purpose: Triple-negative breast cancer (TNBC) is the most dangerous subtype of breast cancer with high rates of metastasis and recurrence. The efficacy of capecitabine in chemotherapy for TNBC is still controversial. This study evaluated the efficacy and safety of capecitabine combining with standard, adjuvant or neoadjuvant chemotherapy for TNBC.Methods: We systematically searched clinical studies through PubMed, Cochrane library, Embase, Wanfang Database, China Academic Journals (CNKI), and American Society of Clinical Oncology’s (ASCO) annual conference report. Studies were assessed for design and quality by the Cochrane risk of bias tool. A meta-analysis was performed using Review Manager to quantify the effect of capecitabine combined with standard, adjuvant or neoadjuvant chemotherapy on the disease-free survival (DFS) rate and overall survival (OS) rate of TNBC patients. Furthermore, safety analysis was performed to evaluate the adverse events.Results: Twelve randomized controlled clinical trials involving totally 4854 TNBC patients were included, of which 2,214 patients received chemotherapy as control group, and 2,278 patients received capecitabine combining with chemotherapy. The results indicated that capecitabine could significantly improve the DFS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.71–0.90, P = 0.0003] and OS (HR 0.83, 95% CI 0.74–0.93, P = 0.001). In subgroup analysis, the combination of capecitabine and cyclophosphamide exhibited a significant benefit in all outcomes (DFS HR 0.75, 95% CI 0.63–0.90, P = 0.002; OS HR 0.65, 95% CI 0.52–0.80, p < 0.0001). Additionally, defferent dose of capecitabine subgroup showed same significant effect on the results. Safety analysis showed that the addition of capecitabine was associated with a much higher risk of hand-foot syndrome, diarrhea and mucositis or stomatitis.Conclusion: The results showed that adjuvant capecitabine could bring significant benefits on DFS and OS to unselected TNBC patients, the combination of capecitabine and cyclophosphamide could improve the survival rate of patients, although the addition of capecitabine could bring significant side effects such as hand foot syndrome (HFS) and diarrhea.

Download Full-text

Platinum-based neoadjuvant chemotherapy for triple-negative breast cancer: a systematic review and meta-analysis

Journal of International Medical Research ◽

10.1177/0300060520964340 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052096434

Author(s):

Zhen-Yu Li ◽

Zhen Zhang ◽

Xiao-Zhong Cao ◽

Yun Feng ◽

Sha-Sha Ren

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Meta Analysis ◽

Complete Response ◽

Extensive Literature ◽

Extensive Literature Search ◽

Positive Breast Cancer

Background Triple-negative breast cancer (TNBC) is associated with higher aggressiveness and mortality than hormone-positive breast cancer because of the lack of approved therapeutic targets. Patients with TNBC who attain a pathological complete response (pCR) after neoadjuvant chemotherapy have improved survival. Platinum-based agents show promising activity in TNBC; however, their use remains controversial. We conducted a meta-analysis to assess the role of platinum-based agents in neoadjuvant chemotherapy in patients with TNBC. Methods We performed an extensive literature search of the Pubmed, Embase, and Cochrane databases. We calculated pooled odds ratios (OR) with 95% confidence intervals (CI) for the identified studies. Results Eight randomized controlled trials with 1345 patients were included in the analysis. The addition of platinum-based agents improved pCR compared with neoadjuvant therapy based on anthracyclines, cyclophosphamide, taxanes, and fluorouracil (49.1% vs. 35.9%; OR: 1.87, 95% CI: 1.23–2.86). Hematological adverse events were similar in both groups, except for more thrombocytopenia in the platinum-based group (OR: 7.96, 95% CI: 3.18–19.93). Conclusion The addition of platinum-based agents to neoadjuvant chemotherapy improved pCR rates in patients with TNBC, with a slight increase in hematological toxicities. Platinum-based agents might thus be an accessible and economically viable option in patients with TNBC.

Download Full-text

Prognostic Role and Clinical Significance of Tumor-Infiltrating Lymphocyte (TIL) and Programmed Death Ligand 1 (PD-L1) Expression in Triple-Negative Breast Cancer (TNBC): A Systematic Review and Meta-Analysis Study

Diagnostics ◽

10.3390/diagnostics10090704 ◽

2020 ◽

Vol 10 (9) ◽

pp. 704 ◽

Cited By ~ 1

Author(s):

Parisa Lotfinejad ◽

Mohammad Asghari Jafarabadi ◽

Mahdi Abdoli Shadbad ◽

Tohid Kazemi ◽

Fariba Pashazadeh ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Prognostic Value ◽

Triple Negative ◽

Meta Analysis ◽

Disease Free Survival ◽

Cochrane Library ◽

P Value ◽

Programmed Death Ligand 1 ◽

Programmed Death

This meta-analysis aimed to evaluate the prognostic value of tumor-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1), their associations with the clinicopathological characteristics, and the association between their levels in patients with triple-negative breast cancer (TNBC). PubMed, EMBASE, Scopus, ProQuest, Web of Science, and Cochrane Library databases were searched to obtain the relevant papers. Seven studies with 1152 patients were included in this study. Like the level of TILs, there were no significant associations between PD-L1 expression and tumor size, tumor stage, lymph node metastasis, histological grade, and Ki67 (All p-values ≥ 0.05). Furthermore, there was no significant association between PD-L1 expression with overall survival (OS) and disease-free survival (DFS). In assessment of TILs and survival relationship, the results showed that a high level of TILs was associated with long-term OS (hazard ratios (HR) = 0.48, 95% CI: 0.30 to 0.77, p-value < 0.001) and DFS (HR = 0.53, 95% CI: 0.35 to 0.78, p-value < 0.001). The results displayed that tumoral PD-L1 expression was strongly associated with high levels of TILs in TNBC patients (OR = 8.34, 95% CI: 2.68 to 25.95, p-value < 0.001). In conclusion, the study has shown the prognostic value of TILs and a strong association between tumoral PD-L1 overexpression with TILs in TNBC patients.

Download Full-text

Immune checkpoint inhibitors plus neoadjuvant chemotherapy in early triple-negative breast cancer: a systematic review and meta-analysis

BMC Cancer ◽

10.1186/s12885-021-08997-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuanfang Xin ◽

Guoshuang Shen ◽

Yonghui Zheng ◽

Yumei Guan ◽

Xingfa Huo ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Triple Negative ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Efficacy And Safety ◽

Intention To Treat

Abstract Purpose Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients. Methods After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of programmed death protein-1/programmed cell death-Ligand 1(PD-1/PD-L1) inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations. Results Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32–2.78, P < 0.001). The pCR rate also increased in both PD-L1 positive (OR: 1.65; 95% CI: 1.26–2.16, P < 0.001) and PD-L1 negative patients (OR: 1.56; 95% CI: 1.04–2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69–3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42–2.53, P < 0.001). Three RCTs (N = 1615) reported EFS and the results showed that adding PD-1/PD-L1 inhibitors increased EFS (HR 0.65, 95% CI 0.50–0.83, P = 0.0007) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3–4 diarrhea (OR: 2.54; 95% CI: 1.21–5.32; P = 0.01), any grade of adverse effects(AEs)including vomiting (OR: 1.37; 95% CI: 1.00–1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39–15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02–8.39; P < 0.001). Conclusions PD-1/PD-L1 inhibitors combined with chemotherapy can improve pCR rates and EFS, and with an increased incidence of some immune-related AEs compared with chemotherapy alone. NACT plus ICIs might be an option in patients with in PD-L1 positive and high-risk populations with positive nodal disease early TNBC.

Download Full-text

Immune Checkpoint Inhibitors Plus Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis.

10.21203/rs.3.rs-671558/v1 ◽

2021 ◽

Author(s):

Yuanfang Xin ◽

Guoshuang Shen ◽

Yonghui Zheng ◽

Yumei Guan ◽

Xingfa Huo ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Triple Negative ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Efficacy And Safety ◽

Intention To Treat

Abstract Purpose: Some studies have shown that Immune checkpoint inhibitors (ICIs) have a favorable efficacy in advanced triple negative breast cancer (TNBC) patients, but the results are controversial in neoadjuvant chemotherapy (NACT) stage. The purpose of this study is to evaluate the efficacy and safety after NACT plus ICIs in early TNBC patients.Methods: After searching PubMed, EMBASE, the Cochrane library and several mainly oncology conferences up to 30 January 2021 systematically, and define randomized controlled trials (RCTs) exploring the efficacy and safety of PD-1/PD-L1 inhibitors plus neoadjuvant chemotherapy in TNBC patients. The primary endpoint was the pathological complete response (pCR) in intention-to-treat populations (ITT), and the secondary endpoints were event-free survival (EFS) and safety analysis in the ITT populations.Results: Six RCTs (N = 2142) were included in our meta-analysis; NACT plus ICIs increased pCR rates compared with NACT in intention-to-treat (ITT) populations (OR: 1.91; 95% CI: 1.32–2.78, P < 0.001). The pCR rate also increased both in PD-L1 positive (OR: 1.65; 95% CI: 1.26–2.16, P < 0.001) and negative patients (OR: 1.56; 95% CI: 1.04–2.33, P = 0.03), especially in PD-L1 positive patients. The benefit was also observed in nodal-positive populations (OR: 2.52; 95% CI: 1.69–3.77, P < 0.001) and Eastern Cooperative Oncology Group performance-status score (ECOG PS) 0 subgroup (OR: 1.90; 95% CI: 1.42–2.53, P < 0.001). Three RCTs (N = 1615) reported that EFS and the addition of PD-1/PD-L1 inhibitors increased EFS (HR 0.66, 95% CI 0.48–0.92, P = 0.01) in ITT populations with a short follow-up time. In the safety analysis of 2205 patients with early TNBC from five eligible studies, NACT plus ICIs had a higher risk of grade 3-4 diarrhea (OR: 2.54; 95% CI: 1.21–5.32; P = 0.01), any grade of AEs including vomiting (OR: 1.37; 95% CI: 1.00–1.86; P = 0.05), hyperthyroidism (OR: 6.04; 95% CI: 2.39–15.29; P < 0.001), and hypothyroidism (OR: 5.04; 95% CI: 3.02–8.39; P < 0.001).Conclusions: NACT plus ICIs might be an option in patients with early TNBC.

Download Full-text