metaEvidence - study list


	Study	study type RCT OBS RCT + OBS	Pathology	T1	T0	Patients	sample sizes	ROB	Results
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, 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)
	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
	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 (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)
	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)
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)

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