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Platinum is essential in neoadjuvant treatment of triple-negative breast cancer: a network meta-analysis
Junjie Li1,2, Li Chen1,2, Wei Tan3
1Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Objective:
This study aimed to assess the efficacy and safety of various neoadjuvant regimens for patients diagnosed with early-stage or locally advanced triple-negative breast cancer (TNBC).
Methods:
Medline, EMBASE, Cochrane Library, and Web of Science were searched in May 2020 to identify randomized controlled trials (RCTs). Bayesian network meta-analysis (NMA) was performed (Registration: PROSPERO CRD42020223012).
Results:
A total of 35 RCTs involving 8,424 participants were reviewed, of which 22 RCTs with 5,203 patients were included in this NMA focusing on pathologic complete response (pCR). An anthracycline-taxane-based (AT) regimen combined with a platinum (ATPt) [odds ratio (OR) = 2.04, 95% credible interval (CrI): 1.69, 2.48] regimen, and a docetaxel regimen combined with a carboplatin (TCb; OR = 2.16, 95% CrI: 1.20, 3.91) regimen improved pCR beyond that with AT only. AT and ATPt combined with targeted therapy [including bevacizumab (Bev), veliparib, atezolizumab, or pembrolizumab] also improved pCR. Five RCTs included in this NMA reported serious adverse events (SAEs) or grade ≥ 3 AEs. TCb was associated with fewer grade ≥ 3 AEs than was AT (OR = 0.66, 95% CrI: 0.23, 1.72) alone. In contrast, ATPt, AT + Bev, ATPt + Bev, ATPt + veliparib, and ATPt + pembrolizumab were associated with more SAEs than was AT alone.
Conclusions:
In patients with TNBC, platinum-based neoadjuvant regimens ATPt and TCb increase pCR beyond that with AT alone, but TCb appears to be better tolerated than either AT or ATPt. Platinum-based regimens combined with targeted therapies (Bev, PARPi, and PD-1/PD-L1 inhibitor) also improve the pCR rate beyond that with AT alone, but this benefit is accompanied by greater toxicity.
Insights
Platinum-based neoadjuvant regimens like ATPt and TCb significantly improve pathologic complete response (pCR) in triple-negative breast cancer (TNBC). While TCb is better tolerated, adding targeted therapies to platinum regimens increases pCR but also toxicity.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Triple-negative breast cancer (TNBC) presents unique treatment challenges, particularly in early-stage and locally advanced disease.
- Neoadjuvant therapy is a critical component in managing TNBC, aiming to improve surgical outcomes and survival.
- Optimizing neoadjuvant regimens for TNBC requires evaluating efficacy and safety profiles of various treatment combinations.
Purpose of the Study:
- To compare the effectiveness and safety of different neoadjuvant treatment strategies for early-stage and locally advanced TNBC.
- To identify which neoadjuvant regimens yield the highest rates of pathologic complete response (pCR).
- To assess the incidence of serious adverse events (SAEs) associated with various neoadjuvant regimens.
Main Methods:
- A systematic literature search was conducted across Medline, EMBASE, Cochrane Library, and Web of Science up to May 2020.
- Randomized controlled trials (RCTs) were identified and analyzed using Bayesian network meta-analysis (NMA).
- The primary outcome for NMA was pathologic complete response (pCR); secondary outcomes included safety and adverse events.
Main Results:
- The analysis included 22 RCTs with 5,203 patients, focusing on pCR rates.
- Anthracycline-taxane-platinum (ATPt) and docetaxel-carboplatin (TCb) regimens significantly improved pCR compared to anthracycline-taxane (AT) alone.
- Combining platinum-based regimens with targeted therapies (bevacizumab, veliparib, atezolizumab, pembrolizumab) also enhanced pCR but increased SAEs.
Conclusions:
- Platinum-containing neoadjuvant regimens (ATPt, TCb) are superior to AT alone in achieving pCR for TNBC.
- The TCb regimen demonstrates a favorable safety profile with potentially fewer grade ≥ 3 adverse events compared to AT or ATPt.
- While targeted therapies combined with platinum regimens boost pCR, they are associated with increased toxicity, necessitating careful patient selection and monitoring.
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