Yung-Hung Luo1,2,3, Han Liu4, Jason A Wampfler5, Henry D Tazelaar6, Yalun Li7, Tobias Peikert8, Dan Liu7, Konstantinos Leventakos9, Yuh-Min Chen1,2,10, Yanan Yang11,12,13, Shih-Hwa Chiou2,3,14, Ping Yang15,16. 1. Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 2. School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. 3. Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. 4. Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China. 5. Division of Biomedical Statistics and Informatics, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA. 6. Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, AZ, USA. 7. Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China. 8. Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN, USA. 9. Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA. 10. Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan. 11. Thoracic Disease Research Unit, Division of Pulmonary and Critical Care Medicine, College of Medicine and Science, Mayo Clinic, Rochester, MN, USA. 12. Department of Biochemistry and Molecular Biology, College of Medicine and Science, Mayo Clinic, Rochester, MN, USA. 13. Developmental Therapeutics and Cell Biology Programs, Mayo Clinic Cancer Center, Rochester, MN, USA. 14. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. 15. Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, USA. yang.ping@mayo.edu. 16. Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, USA. yang.ping@mayo.edu.
Abstract
BACKGROUND: The efficacy of osimertinib in previously EGFR-TKI-treated NSCLC without identification of T790M mutational status remains unclear in real-world practice. PATIENTS AND METHODS: 417 patients had stage III-IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as ≥ second-line EGFR-TKI were identified. The time to treatment failure and risk of death were analyzed. RESULTS: Higher risk of death was found in EGFR-mutant patients with age ≥ 65 years, non-adenocarcinoma, no surgery or radiation, non-exon 19 deletion/exon 21 L858R, higher ECOG PS (2-4), PD-L1 expression ≥ 50%, and bone/liver/adrenal metastasis (all p < 0.05). Osimertinib as ≥ second-line TKI in patients with/without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib (p = 0.0002; 0.0232, respectively). However, osimertinib-treated patients with T790M did not have superior survival than those without (p = 0.2803). A higher risk of treatment failure for osimertinib was found in males, patients with first-line TKI duration ≤ 12 months, BMI drop > 10%, and PD-L1 expression ≥ 50% (All p < 0.05). Nonetheless, osimertinib as ≥ second-line TKI in patients without identification of 790 M did not have higher risk of treatment failure than those with T790M (p = 0.1236). CONCLUSIONS: This study demonstrates that osimertinib as second line or subsequent TKI in EGFR-TKI-treated patients without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib, in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression ≥ 50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression < 50%. These results suggest that osimertinib as second line or subsequent TKI may be a potential alternative option for the treatment of patients without identification of T790M and PD-L1 expression ≥ 50% is associated with a significantly poor outcome in patients receiving osimertinib.
BACKGROUND: The efficacy of osimertinib in previously EGFR-TKI-treated NSCLC without identification of T790M mutational status remains unclear in real-world practice. PATIENTS AND METHODS: 417 patients had stage III-IV NSCLC harboring EGFR mutation and 154 out of 417 patients receiving osimertinib as ≥ second-line EGFR-TKI were identified. The time to treatment failure and risk of death were analyzed. RESULTS: Higher risk of death was found in EGFR-mutant patients with age ≥ 65 years, non-adenocarcinoma, no surgery or radiation, non-exon 19 deletion/exon 21 L858R, higher ECOG PS (2-4), PD-L1 expression ≥ 50%, and bone/liver/adrenal metastasis (all p < 0.05). Osimertinib as ≥ second-line TKI in patients with/without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib (p = 0.0002; 0.0232, respectively). However, osimertinib-treated patients with T790M did not have superior survival than those without (p = 0.2803). A higher risk of treatment failure for osimertinib was found in males, patients with first-line TKI duration ≤ 12 months, BMI drop > 10%, and PD-L1 expression ≥ 50% (All p < 0.05). Nonetheless, osimertinib as ≥ second-line TKI in patients without identification of 790 M did not have higher risk of treatment failure than those with T790M (p = 0.1236). CONCLUSIONS: This study demonstrates that osimertinib as second line or subsequent TKI in EGFR-TKI-treated patients without identification of T790M revealed lower risk of death compared to first-line first/second generation TKI without subsequent osimertinib, in real-world practice. Additionally, EGFR-mutant patients with PD-L1 expression ≥ 50% had a higher risk of treatment failure for osimertinib and worse overall survival than those with PD-L1 expression < 50%. These results suggest that osimertinib as second line or subsequent TKI may be a potential alternative option for the treatment of patients without identification of T790M and PD-L1 expression ≥ 50% is associated with a significantly poor outcome in patients receiving osimertinib.
Authors: Christian Rolfo; Noy Meshulami; Alessandro Russo; Florian Krammer; Adolfo García-Sastre; Philip C Mack; Jorge E Gomez; Nina Bhardwaj; Amin Benyounes; Rafael Sirera; Amy Moore; Nicholas Rohs; Claudia I Henschke; David Yankelevitz; Jennifer King; Yu Shyr; Paul A Bunn; John D Minna; Fred R Hirsch Journal: J Thorac Oncol Date: 2021-11-10 Impact factor: 15.609