Table 3.
Ongoing clinical trials of systemic treatment alone for the treatment of brain metastases in breast cancer.
| Category | Population characteristics | Phase | Treatment | Primary endpoint | ClinicalTrials.gov NCT identifier | Status*
(study start date) |
|---|---|---|---|---|---|---|
| TT+TT | HER2-positive PD/recurrent BM after RT |
II | Pertuzumab+high-dose trastuzumab | CNS ORR by RANO-BM | NCT02536339 | Active, not recruiting (December 2015) |
| TT+TT | HER2-positive Cohort 4a: untreated BM Cohort 4b: PD of BM without prior T-DM1 Cohort 4c: PD of BM with prior T-DM1 |
II | Neratinib+T-DM1 | CNS ORR by composite criteria | NCT01494662 | Recruiting (February 2012) |
| TT+TT | HER2-positive PD/recurrent BM after HER2-directed therapy** |
I/II (randomized) |
Afatinib+T-DM1 T-DM1 alone |
(a) Safety and tolerability of T-DM1 and Afatinib (b) CNS ORR |
NCT04158947 | Not yet recruiting (January 2020) |
| TT+TT | HER2-positive | I (randomized) |
Tucatinib (b.i.d.)+trastuzumab Tucatinib (q.d.)+trastuzumab |
Maximum tolerated dose | NCT01921335 | Active, not recruiting (August 2013) |
| TT+CT | HER2-positive | II | Pyrotinib+capecitabine | CNS ORR | NCT03691051 | Not yet recruiting (November 2018) |
| TT+CT | HER2-positive Previous CT (anthracycline and taxane) |
II | Pyrotinib+vinorelbine | CNS ORR by RANO-BM | NCT03933982 | Recruiting (December 2018) |
| TT+CT | All molecular subtypes Including LMS Recurrent/PD after WBRT |
II | BEEP (+ITM in patients with LMS) |
CNS ORR by volumetric criteria | NCT01281696 | Completed in October 2013 |
| TT+CT | All molecular subtypes Previous WBRT or SRS |
II | BKM120+capecitabine (+trastuzumab for HER2-positive) |
Clinical benefit rate‡ | NCT02000882 | Completed in March 2019 |
| TT+TT (+OP) |
HER2-positive | II | Cohort A: GDC-0084+trastuzumab Cohort B: GDC-0084+trastuzumab+OP |
CNS ORR by RANO-BM | NCT03765983 | Recruiting (February 2019) |
| CT | All molecular subtypes | II | ANG1005 (+trastuzumab for HER2-positive) |
CNS ORR | NCT01480583 | Completed in October 2015 |
| CT | All molecular subtypes Previous CT (anthracycline, taxane, and capecitabine) |
III (randomized) |
Etirinotecan pegol (NKTR-102) TPC§ |
OS | NCT02915744 | Active, not recruiting (November 2016) |
| CT | All molecular subtypes | II | Eribulin mesylate | CNS PFS at 12 weeks | NCT02581839 | Active, not recruiting (November 2015) |
| CT | All molecular subtypes Previous CT (anthracycline and taxane) PD after RT |
II | Eribulin mesylate | CNS ORR by RANO-BM | NCT03412955 | Recruiting (March 2017) |
| CT+TT | HER2-positive Previous SRS, OP, or WBRT |
I/II (randomized) | Cohort 1, phase I: temozolomide+T-DM1 Cohort 2A, phase II: T-DM1 alone Cohort 2B, phase II: temozolomide+T-DM1 |
(a) Maximum tolerated dose (b) Median time to progression |
NCT03190967 | Recruiting (April 2018) |
From http://clinicaltrials.gov, last accessed April 2020.
Including trastuzumab and/or lapatinib, pyrotinib, and tucatinib.
Defined as the best overall response rate of complete response, partial response, or stable disease in the CNS, reported as sustained for ⩾24 weeks.
One of the following seven agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
BEEP, bevacizumab, etoposide, and cisplatin; b.i.d., bis in die (twice daily); BM, brain metastasis; CNS, central nervous system; CT, chemotherapy; HER2, human epidermal growth factor receptor 2; ITM, intrathecal methotrexate; LMS, leptomeningeal seeding; NCT, National Clinical Trial; OP, operation; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; q.d., quaque die (four times daily); RANO-BM, Response Assessment in Neuro-Oncology Brain Metastases; RT, radiotherapy; SRS, stereotactic radiosurgery; T-DM1, ado-trastuzumab emtansine; TPC, treatment of physician’s choice; TT, targeted therapy; WBRT, whole-brain radiotherapy.