Real world use of radiation for newly diagnosed brain metastases in ALK-positive lung cancer receiving a first line ALK inhibitor

Management paradigms now allow systemic targeted drugs before central nervous system (CNS)-directed radiotherapy (RT) in selected asymptomatic patients with non-small cell lung cancer (NSCLC) with brain metastases (BM). We aim to quantify how novel targeted agents with improved CNS activity, such as second-generation ALK inhibitors (e.g. alectinib), might impact the role of CNS-directed RT.This retrospective, observational, real world patterns of care study used a nationwide electronic health record-derived de-identified longitudinal database. A random sample of patients with ALK+ advanced NSCLC and BM on first-line ALK-inhibitor monotherapy between January 1, 2014 and August 31, 2019 were included. Using an index date of the first instance of BM, the outcome was brain-directed local treatment within four months. Trends over time were reported and tested using multivariable modified Poisson regression with robust error variance, including an indicator of in or after 2017 (when alectinib was approved).Of 352 patients, 146 had BM. 104 received CNS-directed local therapy and 42 did not. The majority (89.4%) were treated with RT alone. Of those receiving RT, stereotactic radiosurgery (SRS) monotherapy was the most common (53%) followed by whole brain radiotherapy (WBRT) alone (39%). On multivariable analysis, those patients who had their first BM in or after 2017 had a decreased rate of receiving local BM treatment versus those prior to 2017 with an adjusted incidence rate ratio (aIRR) 0.63 (95% confidence interval [CI]: 0.41-0.95; p=0.026). We found no change in the proportion of BM treated with WBRT in or after 2017 vs before (aIRR = 0.70; 95% CI: 0.24-2.06; p = 0.517).We found decreasing use of CNS-directed RT in patients with NSCLC with new BM on first-line ALK inhibitors. Clinical outcomes for these patients require continued investigation as physicians may be increasingly comfortable deferring upfront local therapy for BM in lieu of novel targeted agents with improved CNS activity.