Retrospective Review of the Safety of Osimertinib with Thoracic Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Tyrosine Kinase inhibitor [TKI] therapy is the backbone of treatment for patients who progress after definitive treatment for EGFR mutated non-small cell lung carcinoma [NSCLC], or those who are diagnosed with metastatic disease. Evidence from phase II and III clinical trials have suggested that ablative consolidation of oligometastatic or progressive sites leads to improved progression-free, and overall survival. For patients on TKI therapy, there is little information regarding the safety of combining therapy with radiation therapy [RT]. There are 5 FDA approved EGFR TKI's but simertinib is most used today and is the focus of this review. We present the risk of toxicity of concurrent simertinib and thoracic RT in a large institutional cohort. <h3>Materials/Methods</h3> A prospectively collected database of patients treated with simertinib from September 2014 through March of 2021 was reviewed to identify those who had RT at some point in their treatment. 206 individual patients were identified of whom 60 had treatment directed to a thoracic target. 13 patients were treated to 2 metachronous thoracic sites yielding 73 individual treatments. Patient records were retrospectively reviewed to identify practice patterns regarding sequencing of RT and TKI, and the incidence of toxicity. <h3>Results</h3> In these 73 targets, most volumes were treated with SBRT [3-5 fractions] 42(57%). Twenty-one targets (29%) were treated with hypofractionation [8-20 fractions; HFRT], 8(11%) were treated with conventional radiation, [200cGY per fraction; CFR] and 2 with quad shot fractionation [QS]. The median PTV size was 91.25cc (range 8.55cc – 767.95cc). In 43 treatments radiation was delivered concurrently with simertinib, drug was held for 20 radiation treatments, and 10 treatments were delivered before simertinib initiation. Of those tumors treated with continuous simertinib dosing, 28 tumors were treated with SBRT, 13 with HFRT, 1 CFR and 1 with QS. 24 patients were diagnosed with radiation pneumonitis following thoracic RT; 4/11(36%) tumors treated prior to TKI; 6/20(30%) treatments when medication was held; and 14/44(32%) tumors when simertinib was continued through radiation (p=0.14). Most cases of pneumonitis were grade 1-2 and only 2 patients developed grade 3 pneumonitis. Grade 3 pneumonitis was not associated with continuous simertinib dosing. The median PTV for any grade pneumonitis was 112.27cc. Institutional V20 planning constraints were met in all but 1 patient who was treated with CFR. Other toxicities reported included 7 events of esophagitis, and 4 events of dermatitis all of which were grade 1-2. <h3>Conclusion</h3> Patients receiving osimertininb concurrently with thoracic RT did not appear to have higher rates of pneumonitis relative to those who held drug during RT or initiated it after RT. This suggests it is safe to continue simertinib concurrently with thoracic RT when standard planning dose limits are followed.