Table 3.
Summary of studies reporting the efficacy of the third-generation EGFR TKI osimertinib in patients with NSCLC and CNS metastases
| EGFR TKI | Publication | Study description | Treatments | Patient characteristics | Results | |
|---|---|---|---|---|---|---|
| Name/type | Phase | |||||
| Osimertinib | Yang et al. [62] | BLOOM | I | Osimertinib (160 mg/day) | N = 32; patients with EGFR mutations and LMD (n = 11 with T790M mutation) | • 23 patients reached radiological assessment: 10 had improvements, 13 had SD • Same 23 patients reached 12-week neurological assessment: 8 symptomatic patients, 7 improved and 1 had SD; of 15 asymptomatic patients, 2 worsened and 13 remained asymptomatic |
| Goss et al. [96] | Pooled analysis of AURA and AURA2 | II | Osimertinib (80 mg/day) following prior EGFR TKI therapy | N = 50; patients with T790M mutation and brain metastases | • CNS ORR: 54%; CNS CR: 12% • CNS responses observed in 82% of patients within 6 weeks, regardless of prior RT • Median CNS PFS not reached |
|
| Mok et al. [92] | AURA3 | III | Osimertinib (80 mg/day) following prior first-line EGFR TKI therapy vs. chemotherapy (IV pemetrexed 500 mg/m2 plus either carboplatin or cisplatin) | N = 419 (osimertinib, n = 279; platinum-pemetrexed, n = 140); patients with T790M mutation and CNS metastases (osimertinib in patients with CNS metastases, n = 93; platinum-pemetrexed, n = 51) | • Median PFS: osimertinib, 8.5; chemotherapy, 4.2 months • ORR: osimertinib, 71%; chemotherapy, 31% |
|
| Soria et al. [94] | FLAURA | III | First-line osimertinib (80 mg QD) vs. standard of care (erlotinib [150 mg QD] or gefitinib [250 mg QD]) | N = 116 (osimertinib, n = 53; erlotinib/gefitinib, n = 63); patients with Del19 or L858R EGFR mutations and brain metastases | • Median PFS, osimertinib, 15.2 months; erlotinib/gefitinib, 9.6 months • CNS progression: osimertinib, 6%; erlotinib/gefitinib, 15% (all patients, N = 556) |
|
BID twice daily, BM brain metastases, CNS central nervous system, CR complete response, CSF cerebrospinal fluid, EGFR epidermal growth factor receptor, IV intravenous, LM leptomeningeal metastases, LMD leptomeningeal disease, MRI magnetic resonance imaging, NSCLC non-small cell lung cancer, ORR overall response rate, OR overall response, PFS progression-free survival, PR partial response, QD once daily, RT radiation therapy, SD stable disease, TKI tyrosine kinase inhibitor