|
| Trial | Development phase (aProtocol No.) | Study population (sample size/planned enrollment) | Agents under evaluation |
|
| Dimerisation inhibitor (Pertuzumab)/Genentech | |
|
| CLEOPATRA | Randomised phase III (NCT00567190) |
bMBC, 1st line () | Docetaxel + trastuzumab + pertuzumab versus docetaxel + trastuzumab + placebo |
| BO17929 [46] | Phase II | MBC, ≥2nd line, prior trastuzumab () | Pertuzumab + trastuzumab pertuzumab → pertuzumab + trastuzumab on cPD |
| Randomised phase III (NCT01358877) | Adjuvant,
dEBC () | Chemotherapy + trastuzumab + pertuzumab versus chemotherapy + trastuzumab + placebo |
| NeoSphere [48] | Randomised phase II | Neoadjuvant, stage II/III EBC () | Docetaxel + trastuzumab + pertuzumab versus docetaxel + pertuzumab versus docetaxel + trastuzumab versus pertuzumab + trastuzumab |
|
| Antibody-Drug Conjugate (Trastuzumab-DM1)/Genentech | |
|
| MARIANNE | Randomised phase III (NCT01120184) | MBC, 1st line () | T-DM1 + pertuzumab versus T-DM1 + placebo versus trastuzumab + taxane |
| EMILIA | Randomised phase III (NCT00829166) | MBC, ≥2nd line, prior trastuzumab + taxane () | T-DM1 versus lapatinib + capecitabine |
| TDM4450g [53] | Randomised phase II (NCT00679341) | MBC, 1st line () | T-DM1 versus trastuzumab + docetaxel |
| Single-arm phase II (NCT01196052) | Neoadjuvant/adjuvant, stage I-III () after anthracyclines | T-DM1 |
|
| Novel Tyrosine Kinase Inhibitors | |
|
| (i) Neratinib (HK-272)/Pfizer | |
|
| NEFERTT | Randomised phase II (NCT00915018) | MBC, 1st line () | Neratinib + paclitaxel versus trastuzumab + paclitaxel |
| Randomised phase II (NCT00777101) | MBC, ≥2nd line, prior trastuzumab + taxane () | Neratinib monotherapy versus lapatinib + capecitabine |
| Reference [60] | Single-arm phase II (NCT00398567) | MBC, ≥2nd line, prior trastuzumab () | Neratinib + trastuzumab |
| ExteNET | Randomised phase III (NCT00878709) | Adjuvant, node-positive, stage II-III () Completed trastuzumab | Neratinib monotherapy versus placebo |
| FB-7 | Randomised phase II (NCT01008150) | Neoadjuvant, stage IIB-IIIC () | Neratinib + paclitaxel versus trastuzumab + paclitaxel |
|
| (ii) Afatinib (BIBW-2992)/Boehringer Ingelheim | |
|
| LUX-Breast 1 | Randomised phase III (NCT01125566) | MBC, ≥2nd line, prior trastuzumab () | Afatinib + vinorelbine versus trastuzumab + vinorelbine |
| Reference [62] | Single-arm Phase II (NCT00431067) | MBC, ≥2nd line, prior trastuzumab () | Afatinib monotherapy |
|
| (iii) ARRY-380/Array BioPharma | |
|
| Expansion phase I (NCT00650572) | MBC, ≥2nd line () | ARRY-380 monotherapy |
|
| (iv) ARRY-334543/Array BioPharma | |
|
| Phase I (NCT00710736) | Advanced solid tumours () | ARRY-334543 + capecitabine |
|
| Heat-shock protein 90 inhibitors | |
|
| (i) Tanespimycin (17-AAG)/Bristol-Myers Squibb | |
|
| Reference [67] | Single-arm phase II (NCT00773344) | MBC, ≥2nd line, prior trastuzumab () | Tanespimycin + trastuzumab |
|
| (ii) AUY922/Novartis | |
|
| Phase Ib/II (NCT001271920) | MBC, ≥2nd line, prior trastuzumab () | AUY 922 + trastuzumab |
|
| mTOR inhibitors | |
|
| (i) Everolimus (RAD001)/Novartis | |
|
| BOLERO-1 | Randomised phase III (NCT00876395) | MBC, 1st line () | Paclitaxel + trastuzumab + everolimus versus paclitaxel + trastuzumab + placebo |
| BOLERO-3 | Randomised phase III (NCT01007942) | MBC, ≥2nd line, prior trastuzumab + taxane () | Vinorelbine + trastuzumab + everolimus versus vinorelbine + trastuzumab + placebo |
|
Reference [70] | Phase I/II (NCT00426566) | MBC, ≥2nd line, prior trastuzumab () | Everolimus + trastuzumab |
| Single-arm phase II (NCT01283789) | MBC, ≥2nd line, prior trastuzumab () | Everolimus + lapatinib |
|
| (ii) Deforolimus (AP23573)/Ariad | |
|
| Single-arm Phase II (NCT00736970) | MBC, ≥2nd line, prior trastuzumab () | Deforolimus + trastuzumab |
|
| (iii) Temsirolimus (CCI-779)/Wyeth | |
|
| Single-arm phase I/II (NCT01111825) | MBC, ≥2nd line, prior trastuzumab () | Temsirolimus + neratinib |
|
| PI3K inhibitors | |
|
| (i) BKM120/Novartis | |
|
| Single-arm phase Ib/II (NCT01132664) | MBC, ≥2nd line, prior trastuzumab () | BKM120 + trastuzumab |
|
| (ii) BEZ235/Novartis | |
|
| Single-arm phase II (NCT01288092) | MBC, ≥2nd line, prior trastuzumab () | BEZ235 monotherapy |
|
| Angiogenesis inhibitors | |
|
| (i) Bevacizumab/Genentech/Roche | |
|
| AVEREL | Randomised phase III (NCT00391092) | MBC, 1st line () | Docetaxel + trastuzumab + bevacizumab versus docetaxel + trastuzumab |
| ECOG1105 | Randomised phase III (NCT00520975) | MBC, 1st line () | Carboplatin + paclitaxel + trastuzumab + bevacizumab versus carboplatin + paclitaxel + trastuzumab + placebo |
| BETH | Randomised phase III (NCT00625898) | Adjuvant, EBC () | Chemotherapy + trastuzumab + bevacizumab versus chemotherapy + trastuzumab |
|
| (ii) Pazopanib/GlaxoSmithKline | |
|
| Reference [78] | Randomised phase II (NCT00347919) | MBC, 1st line () | Pazopanib + lapatinib versus lapatinib |
| Randomised phase III (NCT00558103) | Inflammatory breast cancer, ≥2nd line () Prior trastuzumab/chemotherapy | Pazopanib + lapatinib versus lapatinib |
|
| IGF-1R inhibitors | |
|
| (i) Cixutumumab (IMC-A12)/Eli Lilly | |
|
| Randomised phase II (NCT00684983) | MBC, ≥2nd line, prior trastuzumab, anthracycline and/or taxane () | Lapatinib + capecitabine + cixutumumab versus
lapatinib + capecitabine |
|
| (ii) BMS-754807/Bristol-Myers Squibb | |
|
| Phase I/II (NCT00788333) | MBC, ≥2nd line, prior trastuzumab () | BMS-754807 + trastuzumab |
|
| Bispecific antibody (MM-111)/Merrimack Pharmaceuticals | |
|
| Phase I/II (NCT01097460) | MBC, ≥2nd line, prior trastuzumab () | MM-111 + trastuzumab |
|
