Ying-Yi Lin1, Hong-Fei Gao2, Xin Yang3, Teng Zhu2, Xing-Xing Zheng4, Fei Ji2, Liu-Lu Zhang2, Ci-Qiu Yang2, Mei Yang2, Jie-Qing Li2, Min-Yi Cheng2, Kun Wang5. 1. Shantou University Medical College, Shantou, 515041, Guangdong, China; Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China. 2. Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China. 3. Shantou University Medical College, Shantou, 515041, Guangdong, China; Department of Anesthesiology, the First Affiliated Hospital of Shantou University Medical College, 57 Changping Road, Shantou, 515041, Guangdong, China. 4. Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China; Southern Medical University, Guangzhou, 510515, Guangdong, China. 5. Shantou University Medical College, Shantou, 515041, Guangdong, China; Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, China. Electronic address: gzwangkun@126.com.
Abstract
BACKGROUND: Evidence for the preferred neoadjuvant therapy regimen in triple-negative breast cancer (TNBC) is not yet established. METHODS: Literature search was conducted from inception to February 12, 2022. Phase 2 and 3 randomized controlled trials (RCTs) investigating neoadjuvant therapy for TNBC were eligible. The primary outcome was pathologic complete response (pCR); the secondary outcomes were all-cause treatment discontinuation, disease-free survival or event-free survival (DFS/EFS), and overall survival. Odd ratios (OR) with 95% credible intervals (CrI) were used to estimate binary outcomes; hazard ratios (HR) with 95% CrI were used to estimate time-to-event outcomes. Bayesian network meta-analysis was implemented for each endpoint. Sensitivity analysis and network meta-regression were done. RESULTS: 41 RCTs (N = 7109 TNBC patients) were eligible. Compared with anthracycline- and taxane-based chemotherapy (ChT), PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with a significant increased pCR rate (OR 3.95; 95% CrI 1.81-9.44) and a higher risk of premature treatment discontinuation (3.25; 1.26-8.29). Compared with dose-dense anthracycline- and taxane-based ChT, the combined treatment was not associated with significantly improved pCR (OR 2.57; 95% CrI 0.69-9.92). In terms of time-to-event outcomes, PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with significantly improved DFS/EFS (HR 0.42; 95% CrI 0.19-0.81). CONCLUSIONS: PD-1 inhibitor plus platinum and anthracycline- and taxane-based ChT was currently the most efficacious regimen for pCR and DFS/EFS improvement in TNBC. The choice of chemotherapy backbone, optimization of patient selection with close follow-up and proactive symptomatic managements are essential to the antitumor activity of PD-1 inhibitor.
BACKGROUND: Evidence for the preferred neoadjuvant therapy regimen in triple-negative breast cancer (TNBC) is not yet established. METHODS: Literature search was conducted from inception to February 12, 2022. Phase 2 and 3 randomized controlled trials (RCTs) investigating neoadjuvant therapy for TNBC were eligible. The primary outcome was pathologic complete response (pCR); the secondary outcomes were all-cause treatment discontinuation, disease-free survival or event-free survival (DFS/EFS), and overall survival. Odd ratios (OR) with 95% credible intervals (CrI) were used to estimate binary outcomes; hazard ratios (HR) with 95% CrI were used to estimate time-to-event outcomes. Bayesian network meta-analysis was implemented for each endpoint. Sensitivity analysis and network meta-regression were done. RESULTS: 41 RCTs (N = 7109 TNBC patients) were eligible. Compared with anthracycline- and taxane-based chemotherapy (ChT), PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with a significant increased pCR rate (OR 3.95; 95% CrI 1.81-9.44) and a higher risk of premature treatment discontinuation (3.25; 1.26-8.29). Compared with dose-dense anthracycline- and taxane-based ChT, the combined treatment was not associated with significantly improved pCR (OR 2.57; 95% CrI 0.69-9.92). In terms of time-to-event outcomes, PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with significantly improved DFS/EFS (HR 0.42; 95% CrI 0.19-0.81). CONCLUSIONS: PD-1 inhibitor plus platinum and anthracycline- and taxane-based ChT was currently the most efficacious regimen for pCR and DFS/EFS improvement in TNBC. The choice of chemotherapy backbone, optimization of patient selection with close follow-up and proactive symptomatic managements are essential to the antitumor activity of PD-1 inhibitor.
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Authors: Yves Boucher; Ashwin S Kumar; Jessica M Posada; Evisa Gjini; Kathleen Pfaff; Mikel Lipschitz; Ana Lako; Dan G Duda; Scott J Rodig; F Stephen Hodi; Rakesh K Jain Journal: NPJ Precis Oncol Date: 2021-06-29