Table 1.
Intracranial effect of tyrosine kinase inhibitors ALK inhibitors and epidermal growth factor receptor (EGFR) inhibitors in trials in non-small cell lung cancer (NSCLC).
| Trial | Treatment | IDCR | ICRR |
|---|---|---|---|
| ALK inhibitors | |||
| PROFILE 1014 (10) | Crizotinib | 56% at 24 weeks | Not described |
| PEM + CBDCA or CDDP | 25% at 24 weeks | Not described | |
| Pooled analysis of Ref. (11) | Crizotinib | 56% at 12 weeks (previously untreated) | 18% (previously untreated) |
| PROFILE 1005 (12) | |||
| PROFILE 1007 (13) | |||
| ASCEND-1 (14) | Ceritinib | 65% (pretreated) | 34.5% |
| 79% (naïve) | |||
| ASCEND-2 (15) | Ceritinib | 80% | 45% |
| ASCEND-3 (16) | Ceritinib | 76.9% | 61.5% |
| NCT01449461 (17) | Brigatinib | 83% (measurable) | 50% |
| 85% (non-measurable) | 31% | ||
| NP28673 (18) | Alectinib | 85.3% | 58.8% (measurable) |
| 84.5% (pretreated) | 46.4% (non-measurable) | ||
| NP28673 and NP28761 (19) | Alectinib | 90.0% (measurable BM) | 64.0% (measurable BM) |
| 85.3% (measurable and/or non-measurable BM) | 42.6% (measurable and/or non-measurable BM) | ||
| 35.8% (prior RT) | |||
| 58.5% (non-prior RT) | |||
| J-ALEX (20) | Alectinib | 92.9% | 85.4% |
| ALTA (21) | Brigatinib | 88% (90 mg) | 36% (90 mg) |
| 83% (180 mg) | 67% (180 mg) | ||
| NCT01970865 (22) | Lorlatinib | Not described | 44% (targetable and non-targetable) |
| 60% (targetable) | |||
| EGFR inhibitors | |||
| Pooled analysis of published data | Erlotinib or gefitinib | 75.7% | 51.8% |
| Fan et al. (23) | |||
| Retrospective analysis | Pulsatile high-dose weekly erlotinib | Not described | 67% |
| Grommes et al. (24) | |||
| LUX-Lung 3 and LUX-Lung 6 (25) | Afatinib | Not assessed | Not assessed |
| BLOOM (26) | Osimertinib | Not described | 76% (33% LM improvement and 43% LM SD) |
| BLOOM (27) | AZD3759 | Not described | 52.4% (measurable) |
IDCR, intracranial disease control rate; ICRR, intracranial response rate; PEM, pemetrexed; CBDCA, carboplatin; CDDP, cisplatin; BM, brain metastases; RT, radiotherapy; LM, leptomeningeal metastases; SD, stable disease.