Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Angiotensin-converting enzyme inhibitor prescription is associated with decreased progression-free survival (PFS) and overall survival (OS) in patients with lung cancers treated with PD-1/PD-L1 immune checkpoint blockers.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20512)
Author(s): Soleine Medjebar, Corentin Richard, Jean-David Fumet, Julie Malo, Arielle Elkrief, Normand Blais, Mustapha Tehfe, Marie Florescu, Romain Boidot, Caroline Truntzer, Bertrand Routy, François Ghiringhelli; Centre Georges Francois Leclerc, Dijon, France; Research Platform in Biological Oncology, Center GF Leclerc, Dijon, France; CGFL, Dijon, France; CRCHUM, Montreal, QC, Canada; McGill University Health Centre, Montréal, QC, Canada; Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada; Centre Hospitalier Universite de Montreal- Hopital Notre Dame, Montreal, QC, Canada; Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada; Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada; Department of Medical Oncology, Center GF Leclerc, Dijon, France, Dijon, France
Background: Angiotensin converting enzyme (ACE) inhibitors are used to treat hyperblood pressure and congestive heart failure. Preclinical evidence show that ACE has a role in both innate and adaptive responses thus suggesting a capacity of ACE to promote antitumor immunity. Interaction between ACE inhibitors and Immune checkpoint blockers (ICB) has not been investigated in cancer patients (pts). Our study evaluated the effect of ACE inhibitors in Non Small cell lung cancer (NSCLC) pts treated with PD-1/PD-L1 inhibitors. Methods: We conducted a retrospective multicohort retrospective analysis of pts treated with PD-1/PD-L1 inhibitors for NSCLC at Dijon Cancer Center, and at the University of Montreal Hospital. ACE inhibitors groups were defined as pts treated with ACE inhibitors given during the treatment with ICB. PFS and OS were compared between both groups among all pts. Statistical analyses were performed using the Kaplan-Meier method and Cox univariate analysis. Multivariate Cox regression analyses was used to adjust for classical prognostic factors. Tumor RNA sequencing were performed and CIBERSORT was used to estimate immune cell infiltration in ACE inhibitors group and None ACE inhibitors group. Results: Among 283 pts included (177 pts from Dijon, and 106 pts from Montreal), 27 (10%) received ACE inhibitors. ACE inhibitors group did not differ from None ACE inhibitors group for main clinical prognostic characteristics. However, ACE inhibitors group are more frequently treated with statin, beta blocker and metformin. ACE inhibitors group had shorter median PFS compared to None ACE inhibitors group : 2.5 vs. 3.8 months, p = 0.02 (HR = 1.7 IC95% 1.1-2.5 p = 0.02 Cox Univariate). The negative impact of ACE inhibitors group was maintained after multivariate analyses adjusting for risk factors (HR = 1.9 IC95% 1.1-3.5 p = 0.02 for PFS and HR = 2.3 IC95% 1.2-4.4 p = 0.01 for OS). RNA sequencing and CIBERSORT analysis underlines that ACE inhibitors group has lower M1 macrophage, activated Mast cells, NK cells and memory activated T cells thus suggesting an immunosuppressive state. Conclusions: ACE inhibitors prescription concomitant to the PD-1/PD-L1 inhibitors treatment impairs the outcome in patients with advanced NSCLC pts. This reduction is independent of classical prognostic factors. Biological date underlines an immunosuppressive state in ACE inhibitors group. These data should be validated in larger cohort.