KEY TAKEAWAYS
- The phase 3 IMPassion131 trial aimed to analyze the prognostic significance of PD-L1 expression in predicting the response of PD-1/PD-L1 checkpoint inhibitors in mTNBC patients.
- The study analyzed 20 clinical trials using RevMan version 5.4 and evaluated ORR, PFS, and OS as primary outcomes.
- Patients with PD-L1 expression had a significantly higher ORR and longer 1-year PFS and 2-year OS than those without PD-L1 expression.
- The potential of PD-L1 expression to predict 1-year PFS was marginally superior with pembrolizumab and significantly enhanced in the first-line setting.
- PD-L1 expression can serve as a valuable biomarker for predicting the effectiveness of PD-1/PD-L1 checkpoint inhibitors and assessing the prognosis of mTNBC patients.
Checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have received approval for the treatment of metastatic triple-negative breast cancer (mTNBC) in patients who exhibit positive expression of PD-L1. The unfavorable outcomes observed in the recent phase III clinical trials IMPassion131 and IMPassion132 have prompted inquiries regarding the effectiveness of PD-1/PD-L1 checkpoint inhibitors and the prognostic significance of PD-L1 expression. The researchers aimed to systematically analyze the biomarker significance of PD-L1 expression in predicting the response of PD-1/PD-L1 checkpoint inhibitors in patients with metastatic triple-negative breast cancer. The efficacy of PD-1/PD-L1 checkpoint inhibitors in combination with or without chemotherapy for metastatic triple-negative breast cancer (mTNBC) is being investigated. The study evaluated the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) as the primary outcomes of interest. The data analysis was conducted using Review Manager (RevMan) version 5.4.
This study incorporated 20 clinical trials, encompassing 3962 metastatic triple-negative breast cancer patients. Among these patients, 2665 (67%) received immune checkpoint therapy, while 1297 (33%) received chemotherapy. The overall objective response rate was found to be 22% (95% confidence interval [CI], 14-30%). Notably, a statistically significant improvement was observed in patients who tested positive for programmed death-ligand 1 (PD-L1+) with an ORR of 1.78 (95% CI, 1.45-2.19, P<0.00001) as compared to those who tested negative for PD-L1 (PD-L1- cohort). The pooled outcome analysis revealed a statistically significant advantage in 1-year progression-free survival (PFS) and 2-year overall survival for patients exhibiting programmed death-ligand 1 (PD-L1) expr I2ession. The 1-year PFS odds ratio was 1.39 (95% confidence interval [CI], 1.04-1.85; P=0.02; I = 0%), while the 2-year OS ORR was 2.47 (95% CI, 1.30-4.69; P=0.006; I2 63%). The results of subgroup analysis have demonstrated that the expression of PD-L1 can effectively serve as a predictor of tumor response and a 2-year overall survival benefit in patients with metastatic triple-negative breast cancer, irrespective of the type of investigational agent, the line of treatment administration, and to some extent, the kind of treatment. The biomarker potential of PD-L1 expression in predicting 1-year progression-free survival was marginally superior with pembrolizumab (P=0.09) compared to atezolizumab (P=0.18). However, it was significantly enhanced when the treatment was administered in the first-line setting (OR 1.38 [95%CI, 1.02-1.87], P=0.04) and chemotherapy was included (OR 1.38 [95%CI, 1.02-1.86], P=0.03). The incidence of immune-related toxicity, both of any grade and grade≥3, was 39% (95%CI, 26%-52%) and 10% (95%CI, 8%-13%), respectively.
The expression of programmed death-ligand 1 (PD-L1) can be a prognostic indicator for the objective response rate and two-year overall survival in patients with metastatic triple-negative breast cancer undergoing treatment PD-1/PD-L1 checkpoint inhibitors. The prediction of one-year progression-free survival is also anticipated in certain patients. The expression of PD-L1 can serve as a valuable biomarker for assessing the effectiveness of PD-1/PD-L1 checkpoint inhibitors in patients with metastatic triple-negative breast cancer.
Source:https://pubmed.ncbi.nlm.nih.gov/36949944/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03125902
Khan M, Du K, Ai M, Wang B, Lin J, Ren A, Chen C, Huang Z, Qiu W, Yuan Y, Tian Y. PD-L1 expression as a biomarker of efficacy of PD-1/PD-L1 checkpoint inhibitors in metastatic triple-negative breast cancer: A systematic review and meta-analysis. Front Immunol. 2023 Mar 6;14:1060308. doi: 10.3389/fimmu.2023.1060308. PMID: 36949944; PMCID: PMC10027008.
