A system review of neoadjuvant immune checkpoint blockade for breast cancer
Yanle Ye1, Zhishan Zhang1, Hong Zhao2
1Central Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.
Background:
The clinical application of immune checkpoint blockade (ICB)-based neoadjuvant therapy has been approved in breast cancer since 2021. However, no studies have evaluated its efficacy and safety in randomized and non-randomized settings. Additionally, there exists controversy about which specific subpopulation can benefit from this management strategy.
Methods:
We searched MEDLINE and EMBASE databases for prospective clinical trials of ICB-based neoadjuvant therapy in breast cancer. Information regarding pathological complete response (pCR), event-free survival (EFS), overall survival (OS), and treatment-related adverse event (TRAE) were pooled to estimate the efficacy and safety. Hazard ratio, relative risk (RR) and their 95% confidence intervals (CIs) were calculated.
Results:
Among 22 eligible trials including 6134 women with resectable breast cancer, there were 11 randomized studies with 5574 patients. Pooled analysis on pCR (RR, 1.38; 95% CI, 1.20-1.58; P<0.001), EFS (hazard ratio, 0.67; 95% CI, 0.54-0.81; P<0.001), and OS (hazard ratio, 0.56; 95% CI, 0.35-0.91; P=0.01) revealed that ICB-based neoadjuvant therapy was associated with favorable outcomes over conventional treatment. Moreover, the benefits of EFS were independent of PD-L1 expression (Pinteraction =0.57) and pCR (Pinteraction =0.37) in neoadjuvant immunotherapy. However, combining ICB with conventional neoadjuvant treatment significantly increased the risk of high-grade TRAE (RR, 1.06; 95% CI, 1.01-1.12; P=0.03), serious TRAE (RR, 1.57; 95% CI, 1.26-1.94; P<0.001), treatment discontinuation due to TRAE (RR, 1.47; 95% CI, 1.14-1.90; P=0.003), and potentially fatal adverse event (RR, 2.25; 95% CI, 0.80-6.31; P=0.12).
Conclusion:
The combination of ICB with conventional neoadjuvant treatment is associated with favorable clinical outcomes and importantly, increased grade 3+ toxicities. Clinicians should meticulously monitor patients to minimize the risk of treatment discontinuation in individuals with potentially curable breast cancer.
Insights
Immune checkpoint blockade (ICB) neoadjuvant therapy improves breast cancer outcomes but increases serious side effects. Careful monitoring is crucial to manage treatment-related adverse events and prevent discontinuation.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Immune checkpoint blockade (ICB) neoadjuvant therapy is approved for breast cancer since 2021.
- Limited data exists on its efficacy and safety in randomized and non-randomized settings.
- Controversy surrounds the specific patient subpopulations that benefit most from ICB neoadjuvant therapy.
Purpose of the Study:
- To evaluate the efficacy and safety of ICB-based neoadjuvant therapy in breast cancer.
- To compare outcomes of ICB neoadjuvant therapy versus conventional treatments.
- To identify patient subgroups that benefit from ICB neoadjuvant therapy.
Main Methods:
- Systematic search of MEDLINE and EMBASE for prospective clinical trials of ICB-based neoadjuvant therapy in breast cancer.
- Pooled analysis of pathological complete response (pCR), event-free survival (EFS), overall survival (OS), and treatment-related adverse events (TRAE).
- Calculation of hazard ratios, relative risks (RR), and 95% confidence intervals (CIs).
Main Results:
- Analysis of 22 trials (6134 patients) showed ICB therapy improved pCR, EFS, and OS compared to conventional treatment.
- EFS benefits were independent of PD-L1 expression and pCR.
- ICB significantly increased high-grade TRAE, serious TRAE, treatment discontinuation due to TRAE, and potentially fatal adverse events.
Conclusions:
- ICB-based neoadjuvant therapy offers favorable clinical outcomes in breast cancer but elevates toxicity risks.
- Increased grade 3+ toxicities necessitate meticulous patient monitoring to minimize treatment discontinuation.
- Further research may clarify optimal patient selection for ICB neoadjuvant therapy.
