metaEvidence - study list


	Study	study type RCT OBS RCT + OBS	Pathology	T1	T0	Patients	sample sizes	ROB	Results
es-BC - HER2 positive - (neo)adjuvant (NA) breast cancer - HER2-positive es-BC - HER2 positive - (neo)adjuvant (NA)
versus lapatinib plus epirubicin and cyclophosphamide followed by docetaxel
	trastuzumab plus epirubicin and cyclophosphamide followed by docetaxel
	GeparQuinto, 2012 J Clin Oncol 2018; 36:1308-1316-. Lancet Oncol 2012; 13:135-44-. NCT00567554	RCT	es-BC - HER2 positive - (neo)adjuvant (NA)	trastuzumab plus epirubicin and cyclophosphamide followed by docetaxel	lapatinib plus epirubicin and cyclophosphamide followed by docetaxel	Women with previouscly untreated unilateral or bilateral primary invasive breast carcinoma, with HER2-positive	309 / 311	NA	conclusif	demonstrated 48 % increase in pCR (PE)
versus paclitaxel followed by doxorubicin plus cyclophosphamide, pertuzumab plus trastuzumab, placebo
	paclitaxel followed by doxorubicin plus cyclophosphamide, pertuzumab plus trastuzumab
	IMpassion-050, 2022 J Clin Oncol 2022; 40:2946-2956-. European Society for Medical Oncology NCT03726879	RCT	es-BC - HER2 positive - (neo)adjuvant (NA)	Atezolizumab plus SOC	Placebo plus SOC	Patients ≥ 18 years old with a primary tumor of > 2 cm, positive lymph node status and histologically confirmed Early Her2-Positive Breast Cancer	226 / 228	low	inconclusive	inconclusive 1 % decrease in pCR ,pCR (PE) inconclusive 33 % decrease in pCR ,pCR (PE) Atezolizumab with neoadjuvant dose-dense doxorubicin/cyclophosphamide–paclitaxel and PH for high-risk, HER2-positive early breast cancer did not increase pCR rates versus placebo in the ITT or PD-L1–positive populations
versus trastuzumab
	trastuzumab emtansine
	KATHERINE, 2019 N Engl J Med 2019; 380:617-628-. Ann Oncol 2021; 32:1005-1014-. Cancer 2020; 126:3132-3139-. Breast Cancer Res Treat 2021; 187:759-768-. NCT01772472	RCT	es-BC - HER2 positive - (neo)adjuvant (NA)	trastuzumab emtasine (T-DM1)	trastuzumab	Patients had histologically confirmed, HER2-positive, nonmetastatic, invasive primary breast cancer and if residual invasive disease after completion of taxane-based neoadjuvant chemotherapy ad and had to have completed at least six cycles (16 weeks) of a conventional preoperative chemotherapy regimen containing a minimum of 9 weeks of taxane-based therapy and 9 weeks of trastuzumab therapy.	743 / 743	high	conclusif	inconclusive 30 % decrease in deaths (OS) (PE) demonstrated 50 % decrease in iDFS (PE)
versus trastuzumab plus endocrine therapy
	trastuzumab emtansine
	Harbeck (TDM-1), 2017 J Clin Oncol 2017; 35:3046-3054-.	RCT	es-BC - HER2 positive - (neo)adjuvant (NA), es-BC - HR positive - (neo)adjuvant (NA)	trastuzumab emtasine	trastuzumab plus endocrine therapy	Women older than 18yr with histologically confirmed unilateral primary BC, no evidence of distant metastasis, ER and/or PR-positive and HER2-positive who were candidates for neoadjuvant chemotherapy were eligible	119 / 129	NA	suggested	suggested 2.9-fold increase in pCR (PE)
	trastuzumab emtasine plus endocrine therapy
	Harbeck (TDM1 plus ET), 2017 J Clin Oncol 2017; 35:3046-3054-. NCT01817452	RCT	es-BC - HER2 positive - (neo)adjuvant (NA), es-BC - HR positive - (neo)adjuvant (NA)	trastuzumab emtasine plus endocrine therapy	trastuzumab plus endocrine therapy	Women older than 18yr with histologically confirmed unilateral primary BC, no evidence of distant metastasis, ER and/or PR-positive and HER2-positive who were candidates for neoadjuvant chemotherapy were eligible	-/-	NA	suggested	suggested 3.0-fold increase in pCR (PE)
la/mBC - HER2 positive - 1st Line (L1) breast cancer - HER2-positive la/mBC - HER2 positive la/mBC - HER2 positive - 1st Line (L1)
versus trastuzumab
	pertuzumab plus trastuzumab
	PERTAIN, 2018 J Clin Oncol 2018; 36:2826-2835-. NCT01491737	RCT	la/mBC - HER2 positive - 1st Line (L1)	pertuzumab plus trastuzumab plus an AI (letrozole or anastrozole)	trastuzumab plus an AI (letrozole or anastrozole)	Postmenopausal patients, with first-line HER2-positive and HR positive disease	129 / 129	NA	conclusif	demonstrated 35 % decrease in progression or deaths (PFS) (PE)
versus trastuzumab plus chemotherapy
	trastuzumab plus endocrine therapy
	SYSUCC-002, 2022 Clin Cancer Res 2022; 28:637-645-. NCT01950182	RCT	la/mBC - HER2 positive - 1st Line (L1), la/mBC - HR-positive - 1st line (L1)	trastuzumab plus endocrine therapy	trastuzumab plus chemotherapy	Female patients aged of 18 or more, with locally histology confirmed mBC, HR-positive (ER and/or PR-positive) and HER2-positive	196 / 196	some concern	inconclusive	inconclusive 12 % decrease in progression or deaths (PFS) (PE)
versus trastuzumab plus docetaxel
	bevacizumab plus trastuzumab plus docetaxel
	AVEREL, 2013 J Clin Oncol 2013; 31:1719-25-. NCT00391092	RCT	la/mBC - HER2 positive - 1st Line (L1)	bevacizumab plus docetaxel plus trastuzumab	docetaxel plus trastuzumab	Patients with HER2-positive measurable or evaluable locally recurrent or metastatic BC, ad received no prior trastuzumab or chemotherapy for LR/MBC	216 / 208	some concern	inconclusive	inconclusive 18 % decrease in progression or deaths (PFS) (PE)
	pertuzumab plus trastuzumab plus docetaxel
	PUFFIN, 2020 Breast Cancer Res Treat 2020; 182:689-697-. NCT02896855	RCT	la/mBC - HER2 positive - 1st Line (L1)	pertuzumab plus trastuzumab plus docetaxel	placebo plus trastuzumab plus docetaxel	Patients with HER2-positive, locally recurrent or metastatic BC, no prior therapy for metastatic disease, 18yr or older.	-/-	NA	suggested	suggested 31 % decrease in progression or deaths (PFS)
	CLEOPATRA, 2012 Lancet Oncol 2020; 21:519-530-. Lancet Oncol 2013; 14:461-71-. N Engl J Med 2015; 372:724-34-. N Engl J Med 2012; 366:109-19-. Breast Cancer Res Treat 2013; 142:89-99-. Ann Oncol 2017; 28:2761-2767-. NCT00567190	RCT	la/mBC - HER2 positive - 1st Line (L1)	pertuzumab plus trastuzumab plus docetaxel	placebo plus trastuzumab plus docetaxel	Patients with locally recurrent, unresectable, or metastatic HER2-positive breast cancer who had not received chemotherapy or biologic therapy for their metastatic disease. They may have received one hormonal treatment for metastatic breast cancer before randomization, and/or adjuvant or neoadjuvant chemotherapy with or without trastuzumab before randomization	402 / 406	low	conclusif	demonstrated 34 % decrease in deaths (OS) (PE) demonstrated 38 % decrease in progression or deaths (PFS) (PE) suggested 31 % decrease in deaths (OS) (extension) suggested 31 % decrease in PFS (extension) more...
la/mBC - HER2 positive - 2nd Line (L2) breast cancer - HER2-positive la/mBC - HER2 positive la/mBC - HER2 positive - 2nd Line (L2)
versus lapatinib
	lapatinib plus trastuzumab
	EGF104900, 2010 J Clin Oncol 2012; 30:2585-92-. Journal of Clinical Oncology NCT00320385	RCT	la/mBC - HER2 positive - 2nd Line (L2)	lapatinib plus trastuzumab	lapatinib monotherapy	Patients with HER2-positive mBC who had experienced progression on prior trastuzumab-based therapy. Patients must have received prior anthracycline- and taxane-based regimens in either the adjuvant or metastatic setting.	148 / 148	some concern	suggested	suggested 26 % decrease in deaths (OS) suggested 26 % decrease in progression or deaths (PFS) (PE)
versus lapatinib plus capecitabine
	neratinib plus capecitabine
	NALA (brain metastases), 2020 Oncologist 2021; 26:e1327-e1338-. J Clin Oncol 2020; 38:3138-3149-. NCT01808573	RCT	la/mBC - HER2 positive - 2nd Line (L2)	neratinib plus capecitabine	lapatinib plus capecitabine	Patients with centrally confirmed HER2-positive mBC, and ≥ 2 previous HER2-directed therapies for mBC. Patients with brain metastases were eligible unless they had symptomatic or unstable brain metastases.For this comparison, patients with brain metastases	51 / 50	some concern	inconclusive	no statistically significant result
	NALA, 2020 Oncologist 2021; 26:e1327-e1338-. J Clin Oncol 2020; 38:3138-3149-. NCT01808573	RCT	la/mBC - HER2 positive - 2nd Line (L2)	neratinib plus capecitabine	lapatinib plus capecitabine	Pateints with centrally confirmed HER2-positive mBC, and ≥ 2 previous HER2-directed therapies for mBC. Patients with brain metastases were eligible unless they had symptomatic or unstable brain metastases.	307 / 314	some concern	conclusif	inconclusive 12 % decrease in deaths (OS) (PE) demonstrated 24 % decrease in progression or deaths (PFS) (PE)
	trastuzumab emtansine
	EMILIA, 2012 N Engl J Med 2012;367:1783-91 Lancet Oncol 2017; 18: 732–42 NCT00829166	RCT	la/mBC - HER2 positive - 2nd Line (L2)	trastuzumab emtansine	lapatinib plus capecitabine	patients with HER2-positive unresectable, locally advanced or metastatic breast cancer, who had previously been treated with trastuzumab and a taxane.	495 / 496	some concern	conclusif	demonstrated 32 % decrease in deaths (OS) (PE) demonstrated 35 % decrease in progression or deaths (PFS) (PE) suggested 25 % decrease in deaths (OS) (extension) demonstrated 73 % increase in objective responses (ORR) (PE)
versus placebo
	neratinib
	ExteNET, 2016 Lancet Oncol. 2017; 18:1688-1700 Lancet Oncol 2016 Mar;17(3):367-377. Ann Oncol 2019 Apr 1;30(4):567-574. Future Oncol 2019 Jul;15(21):2489-2501. Breast Cancer Res 2019; 21:39-. Breast Cancer Res 2019; 21:32-. Clin Breast Cancer 2021; 21:80-91.e7-. NCT00878709	RCT	breast cancer - adjuvant, la/mBC - HER2 positive - 2nd Line (L2)	neratinib	placebo	Women with locally confirmed invasive HER2-positive BC stage 1-3, who had received trastuzumab and chemotherapy.	1420 / 1420	low	conclusif	demonstrated 33 % decrease in iDFS,iDFS (PE) suggested 37 % decrease in RFS/DFS,RFS/DFS
versus trastuzumab emtansine
	trastuzumab deruxtecan
	DESTINY Breast03, 2022 N Engl J Med 2022 Mar 24;386(12):1143-1154. NCT03529110	RCT	la/mBC - HER2 positive - 2nd Line (L2)	trastuzumab deruxtecan	trastuzumab emtansine	patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane	-/-	some concern	suggested	suggested 45 % decrease in deaths (OS),deaths (OS) suggested 72 % decrease in progression or deaths (PFS),progression or deaths (PFS)
versus trastuzumab plus capecitabine
	lapatinib plus capecitabine
	WJOG6110B/ELTOP, 2018 Breast 2018; 40:67-75-. UMIN000005219	RCT	la/mBC - HER2 positive - 2nd Line (L2)	lapatinib plus capecitabine	trastuzumab plus capecitabine	Women, aged 20yr or older, cith HER2-positive mBC or unresectable locally advanced BC who were previously treated with taxanes, with progression on trastuzumab-containing regimens	43 / 43	NA	suggested	inconclusive 19 % decrease in progression or deaths (PFS) (PE)
	tucatinib plus trastuzumab plus capecitabine
	HER2CLIMB, 2020 N Engl J Med 2020 Feb 13;382(7):597-609. J Clin Oncol 2020; 38:2610-2619-. NCT02614794	RCT	la/mBC - HER2 positive - 2nd Line (L2)	tucatinib plus trastuzumab plus capecitabine	placebo plus trastuzumab plus capecitabine	Patients with HER2-positive advanced breast cancer, had previously been treated with trastuzumab, pertuzumab, and trastuzumab emtansine. Patients with brain metastases were included unless they were in need of immediate local intervention (enrolled subsequently), or with untreated brain metastases larger than 2 cm in diameter could be enrolled with approval from the medical monitor.	410 / 202	low	conclusif	demonstrated 34 % decrease in deaths (OS) (PE) demonstrated 46 % decrease in progression or deaths (PFS) (PE)
	HER2CLIMB (patients with brain metastases), 2020 N Engl J Med 2020 Feb 13;382(7):597-609. NCT02614794	RCT	la/mBC - HER2 positive - 2nd Line (L2)	tucatinib plus trastuzumab plus capecitabine	placebo plus trastuzumab plus capecitabine	Patients with HER2-positive advanced breast cancer, had previously been treated with trastuzumab, pertuzumab, and trastuzumab emtansine. Patients with brain metastases were included unless they were in need of immediate local intervention (enrolled subsequently), or with untreated brain metastases larger than 2 cm in diameter could be enrolled with approval from the medical monitor.	198 / 93	low	conclusif	demonstrated 52 % decrease in progression or deaths (PFS) (PE)
versus trastuzumab plus chemotherapy
	margetuximab plus chemotherapy
	SOPHIA, 2021 JAMA Oncol 2021 Apr 1;7(4):573-584. NCT02492711	RCT	la/mBC - HER2 positive - 2nd Line (L2)	margetuximab plus chemotherapy (capecitabine or eribulin or gemcitabine or vinorelbine)	trastuzumab plus chemotherapy (capecitabine or eribulin or gemcitabine or vinorelbine)	Patients with confirmed ERBB2-positive advanced BC by local or optional central testing of themost recent biopsy, and must have had progressive disease after 2 or more lines of prior ERBB2 targeted therapy (including pertuzumab) and 1 to 3 lines of nonhormonal metastatic BC therapy.	266 / 270	some concern	conclusif	inconclusive 11 % decrease in deaths (OS) (PE) demonstrated 24 % decrease in progression or deaths (PFS) (PE) inconclusive 49 % increase in objective responses (ORR) (PE)
versus trastuzumab plus vinorelbine
	afatinib plus vinorelbine
	LUX-Breast 1, 2016 Lancet Oncol 2016; 17:357-366-. NCT01125566	RCT	la/mBC - HER2 positive - 2nd Line (L2)	afatinib plus vinorelbine	trastuzumab plus vinorelbine	Women with histollogically confirmed HER2 overexpressing and metastatic BC. Patient ad to have progressive disease following adjuvant treatment or first-line treatment for metastatic disease with trastuzumab.	339 / 169	some concern	inconclusive	statistically significant 48 % increase in deaths (OS) inconclusive 10 % increase in progression or deaths (PFS) (PE)

es-BC - HER2 positive - (neo)adjuvant (NA) breast cancer - HER2-positive es-BC - HER2 positive - (neo)adjuvant (NA)

la/mBC - HER2 positive - 1st Line (L1) breast cancer - HER2-positive la/mBC - HER2 positive la/mBC - HER2 positive - 1st Line (L1)

la/mBC - HER2 positive - 2nd Line (L2) breast cancer - HER2-positive la/mBC - HER2 positive la/mBC - HER2 positive - 2nd Line (L2)