Table 2.
Prospective studies in EGFR mutant NSCLC patients with BM
| Study | TKI | EGFR mutant NSCLC patients with BM | RR (%) | Survival (months) | CNS ORR (%) Duration of CNS control (months) |
|---|---|---|---|---|---|
| Park 2012, phase II | Erlotinib or Gefitinib | 28 | PR = 83; SD = 11 | PFS = 6,6; OS = 15,9 | Not assessed |
| Yu 2017, phase I | Pulsatile Erlotinib | 34 (only 32% had BM) | CR = 2, PR = 70 | PFS = 9,9 | No patient had progression of an untreated CNS metastasis or developed a new CNS lesion while on study (0%, 95% CI 0–13%) |
| luchi 2013, Phase II | Gefitinib | 41 | ORR = 87.8 | PFS = 14,5; OS = 12,9 |
Response of BM (%) CR 31.7% PR 56.1% CR + PR 87.8% SD 9.8% PD (2.4%) The CNS RR of tumors with exon 19 deletion was superior to those with L858R (100% vs 80%) 14.5 mo |
| Yang 2017 (BRAIN), Phase III) | Icotinib | 85 | – | Intracranial PFS = 10 | HR for intracranial disease progression or death 0·56, 95% CI 0·36–0·90; p = 0·014) |
| Schuler 2016 (LUX-Lung 3/6), Phase III | Afatinib | 35/46 | – | PFS = 11,1–8,2 |
CNS ORR 23 of 28 (82.1%) and 12 of 20 (60.0%) in those with Del19 or L858R mutations, respectively Additionally, in patients with uncommon EGFR mutations and brain metastases, ORR was observed in 3 of 9 patients (33.3%) |
| Park 2016 (Lux-Lung 7), Phase II | Afatinib | 26 | – |
ORR 70 CR 1 PR 69 SD 21 PD 6 DC 91 8,4 |
Not assessed |
| Mok 2017 (AURA 3), Phase II | Osimertinib | 144 (T790M) | – | PFS = 10,1 | Mean response time for CNS metastases: 8.9 months |
| Goss 2017 (AURA, AURA2), Phase II | Osimertinib | 50 (T790M) | CNS ORR = 54 | – |
54 Median CNS duration of response (22% maturity) was not reached (range, 1–15 months); at 9 months, 75% (95% CI 53–88) of patients were estimated to remain in response. Median follow-up for CNS PFS was 11 months; median CNS PFS was not reached (95% CI, 7, not calculable) |
| Yang 2017 (BLOOM), Phase I | Osimertinib | 32 (LM, 11 T790M) | ORR = 43 | – |
LM ORR 63% LM DoR 15.2 mo |
| Soria 2018(FLAURA), Phase III | Osimertinib | 53 | ORR = 75; CNS PD = 6 | CNS PFS = 15,2 | Not assessed |
| Yamaguchi 2021 (OCEAN), Phase II | Osimertinib | 66 |
ORR = 40.5% BMRR = 70% |
PFS = 25.2 OS = 19.8 |
BMRR 66.7 median BMs PFS 25.2 mo |
PR partial response, SD stable disease, CR complete response, PFS progression free survival, OS overall survival, ORR objective response rate, CNS central nervous system, BMRR brain metastases response rate, LM leptomeningeal