2327 - Impact of Radiotherapy-to-Tyrosine Kinase Inhibitor Sequence and Time-Interval on Pneumonitis and Treatment Discontinuation in EGFR/ALK-Mutated Non-Small Cell Lung Cancer
Presenter(s)
A. M. Brown1, R. K. Hales1, V. Lam2, D. Barasa2, T. R. McNutt1, S. Houseknecht2, J. Murray2, and R. Voong1; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2Johns Hopkins University, Baltimore, MD
Purpose/Objective(s): We evaluated if the sequence and time interval of tyrosine kinase inhibitor (TKI) initiation relative to conventional radiation with or without chemotherapy influences the incidence of grade = 2 pneumonitis and consequent TKI discontinuation in patients with EGFR/ALK-mutated non–small cell lung cancer (NSCLC).
Materials/Methods: We reviewed records of patients with EGFR- or ALK-mutated NSCLC treated with conventional RT =50Gy, with or without concurrent chemotherapy ((chemo)RT) from 2019-2023. CTCAE v5.0 defined pneumonitis. Descriptive statistics were used. Fisher’s exact test and univariate logistic regression assessed associations between RT-to-TKI time interval and grade =2 pneumonitis, dichotomized at a 3-month threshold and modeled as a continuous variable, respectively. These tests also evaluated potential RT dosimetric predictors of pneumonitis. A p-value <0.05 was statistically significant.
Results: Among 56 patients, n=14 received upfront TKI followed by (chemo)RT and n=42 received (chemo)RT followed by subsequent TKI. Patients were median 65 years old, 55.4% never-smokers, 89.3% ECOG 0-1, and 91.1% received concurrent chemotherapy. N=20 (35.7%) had stage IV and n=36 (64.3%) had stage II-III disease. Median RT dose to target was 63 Gy. Fourteen (25%) developed grade =2 pneumonitis (upfront-TKI: 5/14 (35.7%)subsequent-TKI: 9/4 (21.4%)). Among upfront-TKI patients, all grade =2 pneumonitis occurred after subsequent RT, with longer median duration of TKI-exposure in patients with vs. without pneumonitis (435 vs. 241 days; OR=1.0001, p=0.92). Among subsequent-TKI patients, pneumonitis occurred at a higher rate with TKI-start =3 months after RT compared to TKI-start =3 months (29.4% vs. 16.0%, p = 0.45; time as a continuous variable: OR = 0.9996, p=0.65). Of the 9 subsequent-TKI patients who developed pneumonitis, 3 occurred after RT and 6 occurred after RT and subsequent-TKI start, resulting in 3 of these 6 patients discontinuing TKI (two grade 2-3 pneumonitis; one death). In the upfront-TKI group, larger PTV trended toward higher pneumonitis risk (OR=1.0073, p=0.08), with a weaker association in subsequent-TKI patients (OR=1.0024, p=0.24).
Conclusion: Shorter RT-to-TKI intervals, =3 month, in patients who start TKI after RT may be associated with increased pneumonitis risk and TKI discontinuation. Larger studies are needed to study RT-to-TKI timing in EGFR/ALK-mutated NSCLC.