Table 3.

Phase 3 randomized clinical trials of drugs for breast cancer

Drug	Trial	Participant	Arms	POM	Status	Reference
a. ER-positive breast cancer
Aromatase inhibitor
Anastrozole	ATAC	9366	Anastrozole vs. tamoxifen vs. anastrozole + tamoxifen	DFS	Completed	ATAC Trialists’ Group.351
Anastrozole	TARGET	668	Anastrozole vs. tamoxifen	TTP, OR	/	Bonneterre et al.385
Anastrozole	The North American	353	Anastrozole vs. tamoxifen	OR, CR, PR, TTP	/	Nabholtz et al.386
Letrozole	/	907	Letrozole vs. tamoxifen	TTP	/	Mouridsen et al.387
Exemestane	SOFT and TEXT	5738	Exemestane + OFS vs. tamoxifen + OFS	DFS	Active, not recruiting	Pagani et al.388
CDK4/6 inhibitor
Abemaciclib	MONARCH 2	669	Abemaciclib + fulvestrant vs. fulvestrant	PFS	Active, not recruiting	Sledge et al.389
Abemaciclib	MONARCH 3	493	Abemaciclib + anastrozole or letrozole vs. anastrozole or letrozole	PFS	Active, not recruiting	Goetz et al.356
Palbociclib	PENELOPE-B	1250	Palbociclib (1 yr) + ET vs. ET	iDFS	Completed	Loibl et al.390
Palbociclib	PALLAS	5760	Palbociclib (2 yrs) + ET vs. ET	iDFS	Active, not recruiting	Mayer et al.391
Palbociclib	monarchE	5637	Abemaciclib + ET vs. ET	iDFS	Active, not recruiting	Johnston et al.392
Palbociclib	PALOMA-3	521	Palbociclib+ fulvestrant vs. fulvestrant	PFS	Completed	Cristofanilli et al.393
Ribociclib	MONALEESA-2	668	Ribociclib+ letrozole vs. letrozole	PFS	Completed	Hortobagyi et al.394
Ribociclib	MONALEESA-3	726	Ribociclib+ fulvestrant vs. fulvestrant	PFS	Completed	Slamon et al.395
Ribociclib	MONALEESA-7	672	Ribociclib+ ET vs. ET	PFS	Completed	Lu et al.396

b. HER2-positive breast cancer
Monoclonal antibody
Trastuzumab	HERA	5099	Trastuzumab (2 yrs) vs. trastuzumab (1 yr) vs. observation	DFS	Completed	Piccart-Gebhart et al.397
Trastuzumab	NSABP B-31/N9831	3351	Trastuzumab+ chemo. vs. chemo.	DFS	Completed	Romond et al.398
Trastuzumab	BCIRG 006	3222	AC → T vs. AC → TH vs. TCH	DFS	Completed	Slamon et al.399
Pertuzumab	CLEOPATRA	808	Pertuzumab + trastuzumab + docetaxel vs. trastuzumab + docetaxel	PFS	Completed	Swain et al.400
Pertuzumab	APHINITY	4804	Pertuzumab vs. placebo	iDFS	Active, not recruiting	von Minckwitz et al.362
Margetuximab	SOPHIA	536	Margetuximab vs. trastuzumab	PFS	Completed	Rugo et al.401
Tyrosine kinase inhibitor
Lapatinib	NeoALTTO	455	Lapatinib vs. trastuzumab vs. lapatinib + trastuzumab	pCR	Completed	Baselga et al.402
Lapatinib	GeparQuinto	620	Lapatinib+ chemo. vs. trastuzumab+ chemo.	pCR	Completed	Untch et al.403
Lapatinib	NSABP B-41	529	Lapatinib+ chemo. vs. trastuzumab+ chemo. vs. lapatinib + trastuzumab+ chemo.	pCR	/	Robidoux et al.404
Lapatinib	ALTTO	8381	Trastuzumab vs. lapatinib vs. trastuzumab followed by lapatinib vs. trastuzumab + lapatinib	DFS	Completed	Piccart-Gebhart et al.405
Neratinib	NALA	621	Neratinib+ capecitabine vs. lapatinib + capecitabine	PFS	Complete	Saura et al.406
Neratinib	ExteNET	2840	Neratinib vs. placebo	iDFS	Complete	Chan et al.407
Tucatinib	HER2CLIMB	612	Tucatinib + capecitabine + trastuzumab vs. placebo + capecitabine + trastuzumab	PFS	Complete	Murthy et al.408
Antibody–drug conjugates
T-DM1	EMILIA	991	T-DM1 vs. lapatinib + capecitabine	PFS	Complete	Verma et al.365
T-DM1	KATHERINE	1486	T-DM1 vs. trastuzumab	iDFS	Active, not recruiting	von Minckwitz et al.409
T-DXd	DESTINY-Breast03	524	T-DXd vs. T-DM1	PFS	Active, not recruiting	Cortés et al.366

c. TNBC
PD1 inhibitor
Pembrolizumab	SWOG 1418	1155	Pembrolizumab vs. observation	iDFS	Active, not recruiting	/
Pembrolizumab	KEYNOTE-119	622	pembrolizumab vs. chemo.	OS	Completed	Winer et al.410
Pembrolizumab	KEYNOTE-355	847	Pembrolizumab + chemo. vs. chemo.	AEs, PFS, OS	Active, not recruiting	Cortes et al.411
Pembrolizumab	KEYNOTE-522	1174	Pembrolizumab + chemo. vs. chemo.	pCR, EFS	Active, not recruiting	Schmid et al.412
PD-L1 inhibitor
Atezolizumab	IMpassion031	333	Atezolizumab + chemo. vs. chemo.	pCR	Completed	Mittendorf et al.413
Atezolizumab	IMpassion130	902	Atezolizumab + nab-paclitaxel vs. nab-paclitaxel	PFS, OS	Completed	Schmid et al.383
Atezolizumab	IMpassion132	572	Atezolizumabe + chemo. vs. chemo.	OS	Active, not recruiting	/
Avelumab	A-Brave	474	Avelumab vs. observation	DFS	Active, not recruiting	/
PARP inhibitor
Olaparib	OlympiA	1836	Olaparib vs. placebo	iDFS	Active, not recruiting	Geyer et al.414
Olaparib	OlympiAD	302	Olaparib vs. TPC	PFS	Active, not recruiting	Robson et al.415
Veliparib	BROCADE3	509	Veliparib+ carboplatin–paclitaxel vs. carboplatin–paclitaxel	PFS	Active, not recruiting	Diéras et al.416
Talazoparib	EMBRACA	431	Talazoparib vs. TPC	PFS	Completed	Litton et al.417

ER estrogen receptor, HER2 human epidermal growth factor receptor 2, TNBC triple-negative breast cancer, POM primary outcome measures, DFS disease-free survival, TTP time to progression, OR objective response, CR complete response, PR partial response, OFS ovarian functional suppression, PFS progression free survival, AEs adverse event, iDFS invasive disease-free survival, pCR pathologic complete response, OS overall survival, EFS event-free survival, AC → T doxorubicin + cyclophosphamide followed by docetaxel, AC → TH AC followed by docetaxel + Herceptin, TCH docetaxel + carboplatin + Herceptin, TPC physician’s choice