Risk of Recurrent Interstitial Lung Disease (ILD) from EGFR TKI Rechallenge after Osimertinib Induced ILD
Refereed conference paper presented and published in conference proceedings
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AbstractBackground
Central nervous system (CNS) metastases are common among patients with epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC). Chemotherapy (ChT) is the standard treatment for patients with metastatic EGFRm NSCLC patients failing osimertinib but has limited CNS activity. The role of continuing osimertinib concurrently with ChT after osimertinib failure for CNS control is uncertain.
Methods
This retrospective study included patients with metastatic EGFRm NSCLC who progressed on osimertinib and received ChT from 01/11/2017 to 17/03/2023. Primary endpoint is comparison of time to CNS progression between patients treated with osimertinib plus ChT versus ChT alone after progression on osimertinib. Time to CNS progression was defined from the starting date of ChT to radiological progression of CNS metastases. Hazard ratios and 95% confidence interval were estimated by Cox regression.
Results
A total of 180 patients were analyzed. Median age was 62 (34-80). 28 (16%) received osimertinib as first-line treatment. 33 patients continued osimertinib with ChT (OSIM+) and 147 patients received ChT alone (OSIM-). Prior to starting ChT, 30/33 (91%) and 52/147 (35%) patients had known CNS involvement, among which 8 and 27 had received prior whole brain radiotherapy (WBRT), in the OSIM+ versus OSIM- arms respectively. In the total population, osimertinib plus ChT did not reduce risk of CNS progression. In patients with known CNS metastases, osimertinib plus ChT significantly reduced CNS progression. Numerically fewer patients in the OSIM+ arm received salvage WBRT.
Table: 1349P
Total population OSIM+ (n=33) OSIM- (n=147) Hazard Ratio (95% CI) P value
Median PFS – months (95% CI)* 6.2 (5.5-6.8) 4.8 (4.2-5.4) 0.72 (0.48-1.09) 0.12
CNS progression – no. (%) 7 (21) 33 (22) 0.74 (0.33-1.68) 0.88
Patients with known CNS metastases (n=30) (n=52)
Median PFS – months (95% CI)* 6.2 (5.6-6.7) 4.8 (4.1-5.5) 0.62 (0.38-1.00) 0.05
CNS progression – no. (%) 6 (20) 24 (46) 0.32 (0.13-0.81) 0.02
Salvage WBRT – no. (%) 2 (7) 11 (21) 0.24 (0.05-1.08) 0.06
*CNS/systemic progression or death PFS, progression free survival
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Conclusions
Continuing osimertinib concurrently with ChT after osimertinib failure may reduce CNS progression in patients with known CNS metastasis, and the risk of being subjected to WBRT. Future prospective study is warranted to address this issue
Central nervous system (CNS) metastases are common among patients with epidermal growth factor receptor mutation positive (EGFRm) non-small cell lung cancer (NSCLC). Chemotherapy (ChT) is the standard treatment for patients with metastatic EGFRm NSCLC patients failing osimertinib but has limited CNS activity. The role of continuing osimertinib concurrently with ChT after osimertinib failure for CNS control is uncertain.
Methods
This retrospective study included patients with metastatic EGFRm NSCLC who progressed on osimertinib and received ChT from 01/11/2017 to 17/03/2023. Primary endpoint is comparison of time to CNS progression between patients treated with osimertinib plus ChT versus ChT alone after progression on osimertinib. Time to CNS progression was defined from the starting date of ChT to radiological progression of CNS metastases. Hazard ratios and 95% confidence interval were estimated by Cox regression.
Results
A total of 180 patients were analyzed. Median age was 62 (34-80). 28 (16%) received osimertinib as first-line treatment. 33 patients continued osimertinib with ChT (OSIM+) and 147 patients received ChT alone (OSIM-). Prior to starting ChT, 30/33 (91%) and 52/147 (35%) patients had known CNS involvement, among which 8 and 27 had received prior whole brain radiotherapy (WBRT), in the OSIM+ versus OSIM- arms respectively. In the total population, osimertinib plus ChT did not reduce risk of CNS progression. In patients with known CNS metastases, osimertinib plus ChT significantly reduced CNS progression. Numerically fewer patients in the OSIM+ arm received salvage WBRT.
Table: 1349P
Total population OSIM+ (n=33) OSIM- (n=147) Hazard Ratio (95% CI) P value
Median PFS – months (95% CI)* 6.2 (5.5-6.8) 4.8 (4.2-5.4) 0.72 (0.48-1.09) 0.12
CNS progression – no. (%) 7 (21) 33 (22) 0.74 (0.33-1.68) 0.88
Patients with known CNS metastases (n=30) (n=52)
Median PFS – months (95% CI)* 6.2 (5.6-6.7) 4.8 (4.1-5.5) 0.62 (0.38-1.00) 0.05
CNS progression – no. (%) 6 (20) 24 (46) 0.32 (0.13-0.81) 0.02
Salvage WBRT – no. (%) 2 (7) 11 (21) 0.24 (0.05-1.08) 0.06
*CNS/systemic progression or death PFS, progression free survival
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Conclusions
Continuing osimertinib concurrently with ChT after osimertinib failure may reduce CNS progression in patients with known CNS metastasis, and the risk of being subjected to WBRT. Future prospective study is warranted to address this issue
All Author(s) ListM. S. C. Li, K. W. C. Lee, H. H. F. Loong, K. C. Lam, F. S. T. Mok, Y. M. Lau, K. P. Chan, K. K. S. Mok, J. T. Y. Ng, A. C. C. Chen, W. K. Y. Wong, B. H. W. Lam, O. H. Chen, T. S. K. Mok
Name of ConferenceWorld Conference on Lung Cancer (WCLC) 2023
Start Date of Conference09/09/2023
End Date of Conference12/09/2023
Place of ConferenceSingapore
Country/Region of ConferenceSingapore
Proceedings TitleJournal of Thoracic Oncology
Year2023
Volume Number18
Issue NumberSuppl 11
PagesS342 - S342
LanguagesEnglish-United Kingdom
KeywordsOsimertinib, Pneumonitis, TKI rechallenge
