Abstract 969P
Background
The renin-angiotensin system (RAS) is an important signaling system within the tumor microenvironment, promoting both malignant and stromal cell proliferation. Angiotensin II (AngII) is the main effector hormone, acting predominantly by the signaling of angiotensin II type 1 receptor (AT1R). Preclinical data show that AngII increases TGF-β production through AT1R signaling and decreases TGF-β through AT2R signaling. Thus, the overlap of these pathways may have a critical role in carcinogenesis, as well as immune evasion and inhibiting AT1R may enhance clinical responses in combination with immune checkpoint inhibitors (ICI). Here we report efficacy of ICI in patients (pts) with non-small cell lung cancer (NSCLC) concomitantly taking RAS inhibitors (RASi).
Methods
We conducted a single-center, retrospective analysis of NSCLC pts treated with ICI from September 2015 to August 2019. Clinical data was collected and groups were defined as pts treated with Ang receptor blockers (ARBs), Ang converting enzyme inhibitors (ACEi) or none (control) at the time of ICI initiation. Statistical analyses were performed using Cox regression method.
Results
In total, 127 pts with NSCLC were included, where 15 (11.8%) were concomitantly taking ARBs and 20 (15.7%) ACEi. Baseline characteristics were similar in all groups. The ARB group had a prolonged median PFS and OS compared to the control group (HR 0.401, 95%CI 0.174-0.929 and HR 0.438, 95%CI 0.189-1.015, respectively). Interestingly, no statistically impact in PFS (HR 0.872, 95%CI 0.460-1.654) or OS (HR 0.747, 95%CI 0.393-1.419) was observed in ACEi group compared with control group. ARB use was also associated with an increase in ORR (26.7%), in contrast ACEi use was not associated with ORR improvement (12.5%) when compared with pts not taking RASi (14.9%).
Conclusions
Concomitant ARB use was associated with an improvement in PFS, OS and near doubling in ORR with ICI. This same benefit was not seen with ACEi. This discrepancy may be due to selective blockade of AT1R by ARBs. Thus, ARBs prescription concomitant to ICI seems to be associated with better outcomes and tumor response in pts with NSCLC. These results should be validated in prospective trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.