Michal Sternschuss1,2, Rinat Yerushalmi1,2, Ramy R Saleh3, Eitan Amir4, Hadar Goldvaser5,6. 1. Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, 39 Jabotinski St., 49100, Petah Tikva, Israel. 2. Sackler Faculty of Medicine, Tel Aviv University, PO Box 39040, 6997801, Tel Aviv, Israel. 3. Cedars Cancer Center, McGill University Health Center, 1001 Decarie Blvd, Montreal, QC, H4A 3J1, Canada. 4. Division of Medical Oncology, University of Toronto and Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON, M5G 2M9, Canada. 5. Shaare Zedek Medical Center, Oncology Institute, 12 Shmuel Bait St., PO Box 3235, 9103102, Jerusalem, Israel. hadar7g@gmail.com. 6. The Faculty of Medicine, The Hebrew University, Ein Kerem, PO Box 12271, 9112102, Jerusalem, Israel. hadar7g@gmail.com.
Abstract
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.
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.
Entities:
Keywords:
Immune checkpoint inhibitors; Immunotherapy; Neoadjuvant; Pathological complete response; Triple-negative breast cancer