Applicability of the lung immune prognostic index (LIPI) to metastatic triple negative breast cancer (mTNBC) patients treated with immune checkpoint targeted monoclonal antibodies (ICT mAbs)

Abstract

Background: Tumor-infiltrating lymphocytes are prognostic and predictive in TNBC. However, the level of activity of Immune Checkpoint Targeted Monoclonal Antibodies (ICT mAbs) remains low in this indication and biomarkers are needed to select for patients who could benefit from these treatments. Pretreatment LIPI, based on derived NLR (dNLR =neutrophils/[leucocytes-neutrophils]) and lactate dehydrogenase (LDH) assessment has been associated with outcomes for ICT mAbs in advanced NSCLC patients. We tested whether LIPI has the same impact on mTNBC patients' outcome. Methods: Biological and clinical data were retrospectively collected from mTNBC patients treated with ICT mAbs between Jan 2014 & Apr 2018 in our Drug Development Department. Three LIPI risk groups were studied: good (dNLR<3& LDH 3 or LDH>ULN), poor (dNLR>3 & LDH>ULN). The primary endpoint was progression-free survival (PFS) and the secondary endpoint was overall survival (OS). Results: Forty-two patients were included with a median age of 45, 48% were ECOG 0 and the median prior chemotherapy lines was 3. Twenty-one percent of patients received a PD1/PD-L1 inhibitor asmonotherapy, 79% had ICT mAbs combination. The median PFS and OS under ICT mAbs was 1.35 months (IC 95% 1.27; 2.93) and 13.5 months (5.9; not reached) respectively according to RECIST v1.1. LIPI classified 18 patients as good (43%), 18 patients (43%) as intermediate and 6 patients (14%) as poor risk group. Median PFS was 2.65, 1.32 and 0.85 months for good (GP), intermediate (IP) and poor prognosis (PP) respectively (P=0.002). Median OS was 18.10 months for GP, 9.8 months for IP and 1.6 months PP (P=<0.0001). Metastatic cutaneous lesions were also associated with poor PFS with ICT mAbs in our cohort, HR 3.189, P=0.0028. The PDL1 status does not seem to influence LIPI risk groups. Conclusions: Applying baseline LIPI in mTNBC patients is feasible and is correlated with ICT mAbs outcomes for this population. A larger retrospective validation cohort is being evaluated and more data will be available for the ESMO presentation.