Table 1.
Prospective randomized clinical trials for the treatment of brain metastases in breast cancer.
| Category | Author | Population characteristics | Phase | Treatment | Overall survival | Other primary endpoints |
|---|---|---|---|---|---|---|
| RT | Aoyama et al.30 | 1–4 BMs (<3 cm)* | III | SRS alone (n = 67) versus SRS+WBRT (n = 65) |
1 year: 28.4% versus 38.5% (p = 0.42) |
|
| RT | Chang et al.24 | 1–3 BMs (⩽4 cm)* | III | SRS alone (n = 30) versus SRS+WBRT (n = 28) |
1 year: 63% versus 21% (p = 0.003) |
HVLT-R total recall at 4 months (mean posterior probability of decline): 24% versus 52% [p(A >B)** = 96%] |
| RT | Kocher et al.31 | 1–3 BMs* | III | OP or SRS (n = 179) versus OP or SRS+WBRT (n = 180) |
2 years: 22.3% versus 22.6% (p = 0.89) |
Median time to WHO PS deterioration >2: 10.0 months versus 9.5 months (p = 0.71) |
| RT | Brown et al.32 | 1–3 BMs (<3 cm)* | III | SRS alone (n = 111) versus SRS+WBRT (n = 102) |
Median: 10.4 months versus 7.4 months (p = 0.92) |
Cognitive deterioration at 3 months: 63.5% versus 91.7% (p < 0.001) |
| TT+CT | Lin et al.36 | HER2-positive PD after RT/trastuzumab |
II | Lapatinib+capecitabine (n = 13) versus lapatinib+topotecan (n = 9) |
CNS ORR‡: 38% versus 0% |
|
| TT+CT | Cortés et al.37 | HER2-positive PD after trastuzumab ±lapatinib |
II | Afatinib alone (n = 40) versus afatinib+vinorelbine (n = 38) versus TPC (n = 43) |
Clinical benefit rate§ at 12 weeks: 30.0% versus 34.2% versus 41.9%‖ |
Primary tumors were not confined to breast cancer.
Bayesian probability of a higher neurocognitive decline in SRS+WBRT than SRS alone.
Defined as a ⩾50% volumetric reduction.
Defined as follows: (a) no progression of CNS per RECIST 1.1; (b) no worsening of tumor-related neurological signs or symptoms; (c) no corticosteroid dose increase; and (d) absence of extra-CNS disease progression.
Afatinib alone versus TPC, p = 0.37; afatinib+vinorelbine versus TPC, p = 0.63.
BM, brain metastasis; CNS, central nervous system; CT, chemotherapy; HER2, human epidermal growth factor receptor 2; HVLT-R, Hopkins Verbal Learning Test, Revised; OP, operation; ORR, objective response rate; PD, progressive disease; RECIST, Response Evaluation Criteria In Solid Tumors; RT, radiotherapy; SRS, stereotactic radiosurgery; TPC, treatment of physician’s choice; TT, targeted therapy; WBRT, whole-brain radiotherapy; WHO PS, World Health Organization performance status.