P76.05 Radiotherapy with Concurrent Versus Sequential Osimertinib for Advanced Non-Small Cell Lung Cancer: a Multi-Center Toxicity Analysis

The third-generation, irreversible tyrosine kinase inhibitor osimertinib is first-line treatment for advanced non-small cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR). Pre-clinical studies have shown synergistic anti-tumor activity of osmertinib and radiotherapy. However, the safety radiotherapy concurrent has not been reported. Medical records all patients EGFR-mutated NSCLC who received at an academic hospital system were reviewed. Thirty-five 46 courses while taking osimertinib, 27 33 followed by osimertinib; in latter group began within 30 days completing Patients treated unrelated time points disease progression excluded. Toxicity grades experienced during radiation (per Common Terminology Criteria Adverse Events v5.0) compared between versus sequential osimertinib. This series consists 40 females 22 males adenocarcinomas. Radiation was palliative or locally consolidative (96%) but 2 patients. There a trend toward more oligoprogressive (P=0.092) fewer poor performance status (P=0.057) Grade ≥ 3 toxicities did significantly differ those concurrently sequentially (7% 3%, P=0.859). had inferior progression-free survival (PFS) (HR 2.62, 95% CI 1.09–6.29, P=0.031) similar overall 1.39, 0.40–4.81, P=0.60).Tabled 1Patient CharacteristicsConcurrent (%) N=35Sequential N=27PMedian age, years60 (range 40–76)60 38–80)0.740Sex0.563 Female21 (60)19 (70) Male14 (40)8 (30)Smoking status0.469 Never23 (66)14 (52) Former11 (31)11 (41) Current1 (3)2 (7)ECOG0.057 011 (31)10 (37) 116 (46)10 28 (23)2 (7) (0)4 (15) (0)1 (4)Oligoprogressive disease19 (54)8 (30)0.092T classification0.503 T16 (17)9 (33) T216 (46)11 T37 (20)4 T46 (17)3 (11)N classification0.604 N011 N14 (11)1 (4) N217 (49)12 (44) N33 (9)4 (15)M classification0.107 M01 (3)1 M1a7 (20)0 (0) M1b4 (11)4 M1c23 (66)22 (81)Primary tumor lobe0.286 LUL8 (23)5 (19) LLL7 (20)1 RUL11 (31)14 RML2 (6)1 RLL7 (20)6 (22)EGFR mutation0.400 Exon 19 deletion16 L858R12 (34)9 T790M12 (34)6 (22) Other3 (9)6 (22)Osimertinib dose per day0.715 80 mg33 (94)26 (96) mg2 (4)Irradiated metastatic sites0.116 Lung/mediastinum8 (23)0 Brain14 (40)16 (59) C spine2 (6)0 T (6)2 L (6)4 Non-spinous bone13 (37)9 Adrenal gland1 (3)0 Liver2 (6)3 (11) Distant lymph node0 (4)Median follow-up, months6 0–27)5 1–42)0.426 Open table new tab Treatment confers acceptable acute toxicity. finding clinically significant, as delaying holding may adversely impact control. observed PFS benefit likely driven selection bias osimertinib-naїve whose yet under evolutionary pressure to acquire resistance, already on