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Efficacy and Safety of Paclitaxel-Based PD-1/PD-L1 Immunotherapies for Triple-Negative Breast Cancer: A Systematic
Youran Dai1,2,3, Tianyin Ruan2, Wenhui Yang1
1The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Background:
Triple negative breast cancer (TNBC) is a deadly subtype of breast cancer with limited treatment options. Currently, programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have become the first choice for breast cancer immunotherapies. Despite paclitaxel being considered a cornerstone drug in breast cancer treatment, the effectiveness, safety, and optimal drug selection for its combination with PD-1/PD-L1 inhibitors remain uncertain.
Methods:
We conducted a systematic review and network meta-analysis, performing a comprehensive literature search across PubMed, Embase, and the Cochrane Library from the inception of each database through May 18, 2024. Selected trials were those that assessed the efficacy and safety of paclitaxel-based PD-1/PD-L1 therapies for the treatment of TNBC. The primary endpoint assessed was overall survival (OS), while secondary outcomes included progression-free survival (PFS), adverse events (AEs), overall response rate (ORR), and Pathological complete response (pCR). This study is registered in PROSPERO under registration number CRD42023429651.
Results:
A total of 8 RCTs meeting our eligibility criteria were included, involving 4626 patients who received either Paclitaxel (Paclitaxel-placebo/chemotherapy) or a combination of durvalumab, pembrolizumab, atezolizumab, toripalimab with paclitaxel. The pooled results demonstrated that Durvalumab combined with Paclitaxel significantly reduced the hazard ratio for OS (surface under the cumulative ranking [SUCRA]: 91.05%) and PFS compared with Paclitaxel alone (SUCRA: 83.52%). Additionally, Durvalumab plus Paclitaxel significantly improved the ORR compared with Paclitaxel (odds ratio [OR]: 2.30; 95% credible interval [CrI]: 1.10-5.20). For safety outcomes, Atezolizumab plus Paclitaxel showed a favorable profile in AEs, with no significant differences observed between groups. In the pCR study, Pembrolizumab plus Paclitaxel was the most effective treatment option (SUCRA: 81.85%).
Conclusions:
When combined with paclitaxel, PD-1/PD-L1 inhibitors exhibit a favorable survival benefit. The combination of Durvalumab and paclitaxel represents the optimal treatment option. In the future, attention should be paid to the TNBC subtypes and drug dosage, as these factors may help to design personalized TNBC treatment programs.
Insights
Durvalumab combined with paclitaxel offers significant survival benefits for triple-negative breast cancer (TNBC) patients. This combination therapy shows improved overall survival and progression-free survival, representing an optimal treatment choice.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options.
- Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors are key in breast cancer immunotherapy.
- The optimal combination of paclitaxel with PD-1/PD-L1 inhibitors for TNBC is under investigation.
Purpose of the Study:
- To systematically evaluate the efficacy and safety of paclitaxel-based PD-1/PD-L1 inhibitor therapies for TNBC.
- To compare various PD-1/PD-L1 inhibitors when combined with paclitaxel.
- To identify the most effective treatment strategies for TNBC.
Main Methods:
- Systematic review and network meta-analysis of randomized controlled trials (RCTs).
- Literature search of PubMed, Embase, and Cochrane Library up to May 18, 2024.
- Primary endpoint: overall survival (OS); secondary endpoints: progression-free survival (PFS), adverse events (AEs), overall response rate (ORR), and pathological complete response (pCR).
Main Results:
- Durvalumab plus paclitaxel significantly improved OS (SUCRA: 91.05%) and PFS (SUCRA: 83.52%) compared to paclitaxel alone.
- Durvalumab plus paclitaxel demonstrated a significantly higher ORR (OR: 2.30) compared to paclitaxel.
- Pembrolizumab plus paclitaxel showed the highest efficacy for pCR (SUCRA: 81.85%), while Atezolizumab plus paclitaxel had a favorable safety profile regarding AEs.
Conclusions:
- Paclitaxel combined with PD-1/PD-L1 inhibitors provides a survival benefit for TNBC patients.
- Durvalumab plus paclitaxel emerges as the optimal treatment strategy.
- Future research should focus on TNBC subtypes and drug dosage for personalized treatment programs.
