PMID- 33745080
OWN - NLM
STAT- MEDLINE
DCOM- 20211021
LR  - 20211021
IS  - 1432-1335 (Electronic)
IS  - 0171-5216 (Linking)
VI  - 147
IP  - 11
DP  - 2021 Nov
TI  - Efficacy and safety of neoadjuvant immune checkpoint inhibitors in early-stage 
      triple-negative breast cancer: a systematic review and meta-analysis.
PG  - 3369-3379
LID - 10.1007/s00432-021-03591-w [doi]
AB  - PURPOSE: There is uncertainty regarding the role of adding immune checkpoint 
      inhibitors (ICIs) to neoadjuvant chemotherapy (NACT) in early-stage 
      triple-negative breast cancer (TNBC). METHODS: We identified randomized 
      controlled trials (RCTs) comparing ICIs combined with NACT to NACT in early-stage 
      TNBC. Efficacy outcomes included pathological complete response (pCR) and 
      event-free survival (EFS). Toxicity data included any grade 3/4 adverse events 
      (AEs), serious AEs, AEs leading to death, common and meaningful AEs associated 
      with chemotherapy and immune-related AEs. Odds ratio (ORs), hazard ratios (HR) 
      and their respective 95% confidence intervals (CI) for efficacy and toxicity were 
      extracted and pooled in a meta-analysis. Differences in the odds for pCR between 
      programmed death ligand 1 (PD-L1) status and between PD-L1 and PD-1 inhibitors 
      were also assessed. RESULTS: Five RCTs comprising 2,075 patients were analyzed. 
      Compared to NACT alone, combination of ICIs and NACT significantly improved pCR 
      (OR 1.75, 95% CI 1.25-2.47, p = 0.001) and EFS (HR 0.66, 95% CI 0.48-0.91, 
      p = 0.01). Magnitude of effect on pCR was similar between PD-L1-positive and 
      PD-L1-negative tumors (p for the subgroup difference = 0.80) and between PD-L1 
      and PD-1 inhibitors (p = 0.27). The combination treatment resulted in higher odds 
      of any grade 3/4 AEs (OR 1.31, p = 0.02) and serious AEs (OR 1.84, p = 0.006), 
      with no statistically significant difference in AEs leading to death (OR 1.67, 
      p = 0.51). Higher magnitude of toxicity was observed for immune-related AEs. 
      CONCLUSION: Combination of ICIs and NACT were associated with improved outcome in 
      early-stage TNBC while increasing toxicity significantly. Longer follow-up is 
      desired to better understand the risk and benefit ratio of this combination.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Sternschuss, Michal
AU  - Sternschuss M
AD  - Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski 
      St., 49100, Petah Tikva, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, PO Box 39040, 6997801, Tel 
      Aviv, Israel.
FAU - Yerushalmi, Rinat
AU  - Yerushalmi R
AD  - Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski 
      St., 49100, Petah Tikva, Israel.
AD  - Sackler Faculty of Medicine, Tel Aviv University, PO Box 39040, 6997801, Tel 
      Aviv, Israel.
FAU - Saleh, Ramy R
AU  - Saleh RR
AD  - Cedars Cancer Center, McGill University Health Center, 1001 Decarie Blvd, 
      Montreal, QC, H4A 3J1, Canada.
FAU - Amir, Eitan
AU  - Amir E
AD  - Division of Medical Oncology, University of Toronto and Princess Margaret Cancer 
      Centre, 610 University Ave, Toronto, ON, M5G 2M9, Canada.
FAU - Goldvaser, Hadar
AU  - Goldvaser H
AUID- ORCID: 0000-0002-9557-4634
AD  - Shaare Zedek Medical Center, Oncology Institute, 12 Shmuel Bait St., PO Box 3235, 
      9103102, Jerusalem, Israel. hadar7g@gmail.com.
AD  - The Faculty of Medicine, The Hebrew University, Ein Kerem, PO Box 12271, 9112102, 
      Jerusalem, Israel. hadar7g@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20210321
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use
MH  - Humans
MH  - Immune Checkpoint Inhibitors/administration & dosage
MH  - Neoadjuvant Therapy
MH  - Neoplasm Staging
MH  - Randomized Controlled Trials as Topic
MH  - Triple Negative Breast Neoplasms/*drug therapy/immunology
OTO - NOTNLM
OT  - Immune checkpoint inhibitors
OT  - Immunotherapy
OT  - Neoadjuvant
OT  - Pathological complete response
OT  - Triple-negative breast cancer
EDAT- 2021/03/22 06:00
MHDA- 2023/02/25 06:00
CRDT- 2021/03/21 21:25
PHST- 2020/12/29 00:00 [received]
PHST- 2021/03/07 00:00 [accepted]
PHST- 2021/03/22 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2021/03/21 21:25 [entrez]
AID - 10.1007/s00432-021-03591-w [pii]
AID - 10.1007/s00432-021-03591-w [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2021 Nov;147(11):3369-3379. doi: 
      10.1007/s00432-021-03591-w. Epub 2021 Mar 21.