Immune-related adverse events (IRAEs) in metastatic lung cancer patients receiving PD-1/PD-L1 inhibitors and thoracic radiotherapy.

Abstract

9079 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are associated with unique IRAEs, including pneumonitis (PNS). Thoracic radiotherapy (TRT) is also associated with PNS but it is unknown whether TRT+ICI increases the risk of PNS or other IRAEs. Furthermore, low serum LDH levels are associated with better response/survival to ICI but its potential role as a biomarker for IRAEs is unexplored. Methods: We retrospectively reviewed 164 pts with metastatic lung cancer (95% NSCLC, 5% SCLC) consecutively treated at our institution from 2013-2016 with PD-1/PD-L1 inhibitors and a minimum of one month follow-up, except in cases of rapid death from an IRAE ( n =4). Pts were grouped according to TRT received (+ vs -). IRAE grades were assigned using NCI CTCAE v4.0. Outcomes were compared using Fisher’s exact test and two-sided Student’s t-test. Results: Baseline characteristics such as age, gender, smoking status, supplemental oxygen requirement, median number of chemotherapy lines prior to ICI (1 vs 1), median ICI cycles (5 vs 3), and median follow-up after ICI initiation (8 vs 7 months) were similar in the +TRT ( n = 73) and -TRT ( n =91) groups. Rates of grade ≥ 2 IRAEs (18.1 vs 14.4%, p = 0.67), all-grade PNS (8.2 vs 5.5%, p= 0.54), and grade ≥ 2 PNS (4.1 vs 3.3%, p = 1) were not significantly different between the +TRT and -TRT cohorts. Mean TRT dose was similar between those pts who developed PNS and those who did not (55.8 vs 55.9 Gy). In the +TRT group, 85% received TRT a median of 8.6 months before ICI. Among 7 pts (10%) who had concurrent TRT+ICI, none developed symptomatic PNS. Patients who developed grade ≥ 2 IRAEs ( n= 26) had significantly higher mean serum LDH before initiation of ICI than patients who did not (283 vs 214, ref 98-192 IU/L, p= 0.03). Conclusions: TRT in lung cancer pts receiving ICI was not associated with increased risk of PNS in this series. LDH may be a negative predictive biomarker as pts who suffered grade ≥ 2 IRAEs had significantly higher baseline LDH than those who did not. Larger cohorts and prospective studies would be helpful to validate these findings.