Immune checkpoint inhibitor (ICI) efficacy in triple-negative breast cancer (TNBC) patients with liver metastases (LM): A meta-analysis.

Abstract

e13131 Background: TNBC is an aggressive breast cancer (BC) subtype, and the only subtype where ICIs are approved. Approximately 50% of patients (pts) develop distant metastases, with LM occurring in 8-30% of TNBC cases and being associated with poor prognosis. The liver’s immunocompromised state may limit immunotherapy effectiveness. This meta-analysis synthesizes findings from clinical trials evaluating the efficacy of ICIs in TNBC-LM pts. Methods: A systematic literature search was conducted utilizing PubMed, Embase, and Cochrane Review to identify trials comparing hazard ratios (HR) in pts with TNBC-LM and non-LM. Six randomized controlled trials (four Phase III: IMpassion130, IMpassion131, IMpassion132, KEYNOTE119, two Phase II: ALICE, TBCRC043) were identified that had available efficacy data. Data extracted included number of pts and clinical outcomes for intention to treat (ITT) and programmed death-ligand1 (PD-L1) positive groups and by with LM/without LM. Log-transformed hazard ratio (HRs) and standard errors were calculated. A random-effects model was utilized. Heterogeneity was assessed using the I 2 statistic. Results: 2273 pts were included, 754/2273 had LMs. Progression free survival (PFS) was similar among all pts (HR 0.83 [0.75,0.92]), in pts with liver metastases (HR 0.66 [0.43,1.00]) and in pts without liver metastases (HR 0.78 [0.65,0.92]). PFS was statistically significant for PD-L1+ pts (HR: 0.74 [0.63, 0.88]), but not for those with LM (HR 0.78 [0.60, 1.00]), or those without LM (HR: 0.93 [0.72, 1.20]). Overall survival was improved for pts without LM with PDL1 + disease HR 0.80 [0.66,0.97]. The low heterogeneity in most analyses strengthens the reliability of pooled estimates. Conclusions: We observed PFS benefit for both TNBC-LM and without-LM pts receiving ICIs. Limited pts had PDL1 + data reported which limited analysis by PD-L1 status. Our study highlights that although LM could be an immunocompromised site of disease, pts still benefit from ICI therapy. Future studies could focus on deciphering the tumor microenvironment of LM as an area of translational research. OS and PFS by liver metastases and PD-L1 status. Group OS PFS ITT HR: 0.93 [0.84, 1.01], I 2 : 29%, p=0.096 HR: 0.83 [0.75, 0.92], I 2 : 25.2%, p<0.001 PD-L1+ HR: 0.87 [0.72, 1.04], I 2 : 40%, p=0.11 HR: 0.74 [0.63, 0.88], I 2 : 0.0%, p<0.001 LM HR: 0.91 [0.72, 1.15], I 2 : 20%, p=0.428 HR: 0.66 [0.43, 1.00], I 2 : 30.0%, p=0.048 Without-LM HR: 0.92 [0.80, 1.05], I 2 : 0%, p=0.211 HR: 0.78 [0.65, 0.92], I 2 : 0.0%, p=0.004 LM-PDL1+ HR: 0.88 [0.70, 1.09], I 2 : 4%, p=0.231 HR: 0.78 [0.60, 1.00], I 2 : 0.0%, p=0.051 Without-LM-PD-L1+ HR: 0.80 [0.66, 0.97], I 2 : 28%, p=0.025 HR: 0.93 [0.72, 1.20], I 2 : 0.0%, p=0.572