metaEvidence - study list


	Study	study type RCT OBS RCT + OBS	Pathology	T1	T0	Patients	sample sizes	ROB	Results
breast cancer (BC) breast cancer (BC)
versus GM-CSF
	AE37 vaccine plus GM-CSF
	Brown (AE37 plus GM-CSF vs GM-CSF), 2020 Breast Cancer Res Treat 2020; 181:391-401-. NCT00524277	RCT	breast cancer (BC)	AE37 plus GM-CSF	GM-CSF	Patients with HER2-positive, lymph node-positive breast cancer or high-risk lymph node-negative breast cancer.	154 / 147	high	inconclusive	inconclusive 1 % decrease in RFS/DFS (PE)
	GP2 vaccine plus GM-CSF
	Brown (GP2 plus GM-CSF vs GM-CSF), 2020 Breast Cancer Res Treat 2020; 181:391-401-. NCT00524277	RCT	breast cancer (BC)	GP2 plus GM-CSF	GM-CSF	Patients with HER2-positive, lymph node-positive breast cancer or high-risk lymph node-negative breast cancer.	89 / 91	high	inconclusive	inconclusive 3 % decrease in RFS/DFS (PE)
breast cancer - adjuvant breast cancer - adjuvant
versus endocrine therapy
	abemaciclib plus endocrine therapy
	MonarchE, 2021 Oncologist 2021; 26 Suppl 2:S5-S6-. J Clin Oncol 2020 Dec 1;38(34):3987-3998. Ann Oncol 2021; 32:1571-1581-. NCT03155997	RCT	la/mBC - HR-positive - 1st line (L1)	abemaciclib plus endocrine therapy	endocrine therapy	Patients (women and men) with HR-positive and HER2-negative breast cancer. Radiotherapy and both adjuvant and neoadjuvant chemotherapy were allowed, but not required.	2808 / 2829	high	conclusif	demonstrated 25 % decrease in iDFS (PE)
	palbociclib
	PALLAS, 2022 J Clin Oncol 2022; 40:282-293-. Lancet Oncol 2021; 22:212-222-. J Clin Oncol 2022; 40:449-458-. NCT02513394	RCT	breast cancer - adjuvant			Patients with histollogically confirmed stage II or III HR-positive BC. Before random assignment, patients had completed definitive breast surgery (and (neo)adjuvantchemotherapy and/or radiotherapy, if indicated)	2884 / 2877	NA	inconclusive	no statistically significant result
	palbociclib plus endocrine therapy
	PENELOPE-B, 2021 J Clin Oncol 2021; 39:1518-1530-. Oncologist 2021; 26 Suppl 2:S7-S8-. NCT01864746	RCT	la/mBC - HR-positive - 1st line (L1)	palbociclib plus endocrine therapy according to local standars (physician's choice)	placebo plus endocrine therapy according to local standars (physician's choice)	Women with residual invasive disease after NACT (NACT during at least 16 weeks) in the breats or in lymph nodes, ER and/or PR positive and HER2 negative tumor.	628 / 616	low	inconclusive	inconclusive 7 % decrease in iDFS (PE)
versus placebo
	everolimus
	Bachelot, 2022 J Clin Oncol 2022 May 23;JCO2102179. NCT01805271	RCT	breast cancer - adjuvant	everolimus for 2 years combined with standard endocrine therapy	placebo for 2 years combined with standard placebo	women with high-risk, hormone receptor-positive, human epidermal growth factor receptor 2-negative primary breast cancer	-/-	NA	inconclusive	no statistically significant result
	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
	olaparib
	OlympiA (BIG 6-13, NSABP B-55) unpublished New England Journal of Medicine NCT02032823	RCT	es-BC - TNBC - NA - all population	olaparib	placebo	patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors	921 / 915	NA	conclusif	demonstrated 32 % decrease in deaths (OS) (PE) demonstrated 42 % decrease in iDFS (PE)
	pembrolizumab alone
	KEYNOTE-522, 2020 N. Engl. J. Med. 2020; 382:810-821 N Engl J Med 2022; 386:556-567-. NCT03036488	RCT	es-BC - TNBC - NA - all population	pembrolizumab	placebo	previously previously untreated, nonmetastatic disease, stage II or stage III, triple-negative breast cancer treated with paclitaxel and carboplatin, treated for neoadjuvant phase and an adjuvant phase;	784 / 390	low	conclusif	demonstrated 12.6-fold increase in pCR (PE) suggested 37 % decrease in events or deaths (EFS) (PE)
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)
es-BC - HER2 negative - (neo)adjuvant (NA) breast cancer - HER2-positive es-BC - HER2 negative - (neo)adjuvant (NA)
versus paclitaxel followed by doxorubicin plus cyclophosphamide
	pembrolizumab plus paclitxel followed by doxorubicin plus cyclophosphamide
	I-SPY2, 2020 JAMA Oncol 2020 May Cancer 2014; 120:773 JAMA Oncol 2020 Sep 1;6(9):1355-1362. NCT01042379	RCT	es-BC - HER2 negative - (neo)adjuvant (NA)	pembrolizumab plus paclitxel followed by doxorubicin plus cyclophosphamide	paclitaxel followed by doxorubicin plus cyclophosphamide	Patients with ERBB2 (formerly HER2)-negative breast cance, women treated with neoadjuvant for early-stage breast cancer (stage II or III)	69 / 181	high	inconclusive	suggested 2.7-fold increase in pCR (PE)
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 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, 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)
es-BC - HR positive - (neo)adjuvant (NA) breast cancer - HR positive es-BC - HR positive - (neo)adjuvant (NA)
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)
es-BC - HR-positive - 1st line (L1) breast cancer - HR positive es-BC - HR-positive - 1st line (L1)
versus letrozole
	taselisib plus letrozole
	LORELEI, 2019 Lancet Oncol 2019; 20:1226-1238-. NCT02273973	RCT	es-BC - HR-positive - 1st line (L1)	taselisib plus letrozole	placebo plus letrozole	Postmenopausal women (aged >= 18yr), with operable stage I-III invasive BC HR-positive (ER positive) and HER2-negative	166 / 168	low	suggested	suggested 55 % increase in objective responses (ORR) (PE) inconclusive 2.1-fold increase in pCR (PE)
la/mBC - HR positive breast cancer - HR positive la/mBC - HR positive
versus capecitabine
	palbociclib plus endocrine therapy
	KCSG-BR15-10, 2019 Lancet Oncol 2019; 20:1750-1759-. NCT02592746	RCT	la/mBC - HR positive	palbociclib plus exemestane	capecitabine	Premenopausal women aged 19 years or older with histologically confirmed, hormone receptor-positive, HER2-negative metastatic or recurrent breast cancer were eligible.	92 / 86	NA	suggested	suggested 34 % decrease in progression or deaths (PFS) (PE)
versus fulvestrant
	buparlisib plus fulvestrant
	BELLE-2 (patients with known PI3K status), 2017 Lancet Oncol 2017; 18:904-916-. NCT01610284	RCT	la/mBC - HR positive	buparlisib plus fulvestrant	placebo plus fulvestrant	Postmenopausal women (>=18yr), with histollogically confirmed HR-positive and HER2-negative inoperable locally advanced or metastatic breast cancer (with progession on or after aromatase ihnibitor treatment). This subgroup population included ptients with a PI3K status known (activated or not)	427 / 424	low	conclusif	inconclusive 9 % decrease in deaths (OS) (PE) demonstrated 20 % decrease in progression or deaths (PFS) (PE)
la/mBC - HR positive - (neo)adjuvant (NA) breast cancer - HR positive la/mBC - HR positive la/mBC - HR positive - (neo)adjuvant (NA)
versus letrozole
	alpelisib plus letrozole
	NEO-ORB (wild type cohort), 2019 Clin Cancer Res 2019; 25:2975-2987-. NCT01923168	RCT	la/mBC - HR positive - (neo)adjuvant (NA)	alpelisib plus letrozole	letrozole	Postmenopausal women with locally confirmed, HR , HER2−, T1c-T3 operable breast cancer with known PIK3CA mutation status, who had not previously received treatment with local or systemic therapy and were considered eligible for neoadjuvant endocrine therapy were included in this study.	131 / 126	NA	inconclusive	inconclusive 11 % increase in objective responses (ORR) (PE) inconclusive 68 % increase in pCR (PE)
	NEO-ORB (mutant cohort), 2019 Clin Cancer Res 2019; 25:2975-2987-. NCT01923168	RCT	la/mBC - HR positive - (neo)adjuvant (NA)	alpelisib plus letrozole	letrozole	Postmenopausal women with locally confirmed, HR , HER2−, T1c-T3 operable breast cancer with known PIK3CA mutation status, who had not previously received treatment with local or systemic therapy and were considered eligible for neoadjuvant endocrine therapy were included in this study.	-/-	NA	inconclusive	inconclusive 6 % decrease in objective responses (ORR) (PE) inconclusive 45 % decrease in pCR (PE)
la/mBC - HR-positive - 1st line (L1) breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 1st line (L1)
versus aromatase inhibitor
	abemaciclib plus aromatase inhibitor
	MONARCH 3, 2017 J Clin Oncol 2017 Nov 10;35(32):3638-3646. Oncologist 2020; 25:e1346-e1354-. NCT02246621	RCT	la/mBC - HR-positive - 1st line (L1)	abemaciclib plus a nonsteroidal aromatase inhibitor	placebo plus a nonsteroidal aromatase inhibitor	Postmenopausal women (aged 18 or more)with locally advanced HR-positive, HER2-negative locoregionally recurrent BC	328 / 165	low	conclusif	demonstrated 46 % decrease in progression or deaths (PFS) (PE)
versus endocrine therapy
	abemaciclib plus endocrine therapy
	MonarchE, 2021 Oncologist 2021; 26 Suppl 2:S5-S6-. J Clin Oncol 2020 Dec 1;38(34):3987-3998. Ann Oncol 2021; 32:1571-1581-. NCT03155997	RCT	la/mBC - HR-positive - 1st line (L1)	abemaciclib plus endocrine therapy	endocrine therapy	Patients (women and men) with HR-positive and HER2-negative breast cancer. Radiotherapy and both adjuvant and neoadjuvant chemotherapy were allowed, but not required.	2808 / 2829	high	conclusif	demonstrated 25 % decrease in iDFS (PE)
	palbociclib plus endocrine therapy
	PENELOPE-B, 2021 J Clin Oncol 2021; 39:1518-1530-. Oncologist 2021; 26 Suppl 2:S7-S8-. NCT01864746	RCT	la/mBC - HR-positive - 1st line (L1)	palbociclib plus endocrine therapy according to local standars (physician's choice)	placebo plus endocrine therapy according to local standars (physician's choice)	Women with residual invasive disease after NACT (NACT during at least 16 weeks) in the breats or in lymph nodes, ER and/or PR positive and HER2 negative tumor.	628 / 616	low	inconclusive	inconclusive 7 % decrease in iDFS (PE)
versus exemestane plus ridaforolimus
	dalotuzumab plus ridaforolimus plus exemestane
	MK-8669-064, 2017 Breast Cancer Res Treat 2017; 165:601-609-. NCT01605396	RCT	la/mBC - HR-positive - 1st line (L1)	dalotuzumab plus ridaforolimus plus exemestane	ridaforolimus plus exemestane	Patients with metastatic or locally advanced ER-positive and HER2-negative BC	40 / 40	some concern	inconclusive	inconclusive 18 % increase in progression or deaths (PFS) (PE)
versus fulvestrant
	cediranib plus fulvestrant
	NCT00454805, 2013 Invest New Drugs 2013; 31:1345-54-. NCT00454805	RCT	la/mBC - HR-positive - 1st line (L1)	cediranib plus fulvestrant	fulvestrant	Postmenopausal women with histologically/cytologically confirmed hormone-sensitive BC, with evidence of metastatic disease.	-/-	high	inconclusive	inconclusive 13 % decrease in progression or deaths (PFS) (PE)
	lapatinib plus fulvestrant
	CALGB 40302, 2014 J Clin Oncol 2014; 32:3959-66-. NCT00390455	RCT	la/mBC - HR-positive - 1st line (L1)	lapatinib plus fulvestrant	placebo plus fulvestrant	Postmenauposal women with stage III or IV HR-positive BC (Er and/or PR positive). Originally with HER2-positive, then an amendment to include tumors regardless of HER2 status. Patients had one or two prior endocrine treatments for at least 3 months without tumor progression in either the adjuvant or metastatic setting.	-/-	NA	suggested	inconclusive 4 % increase in progression or deaths (PFS) (PE)
versus letrozole
	lapatinib plus letrozole
	EGF30008 (all population), 2009 J Clin Oncol 2009; 27:5538-46-. NCT00073528	RCT	la/mBC - HR-positive - 1st line (L1)	lapatinib plus letrozole	placebo plus letrozole	Postmenopausal women with histologically confirmed stage IIIB/IIIC or IV, with HR positive. No prior therapy for advanced/metastatic BC was allowed, bu prior (neo)adjuvant antiestrogen therapy was allowed.	642 / 644	NA	conclusif	demonstrated 14 % decrease in progression or deaths (PFS) (PE)
	EGF30008 (HER2-positive), 2009 J Clin Oncol 2009; 27:5538-46-. NCT00073528	RCT	la/mBC - HR-positive - 1st line (L1)	lapatinib plus letrozole	placebo plus letrozole	Postmenopausal women with histologically confirmed stage IIIB/IIIC or IV, with HR positive. No prior therapy for advanced/metastatic BC was allowed, bu prior (neo)adjuvant antiestrogen therapy was allowed.	111 / 108	NA	conclusif	demonstrated 29 % decrease in progression or deaths (PFS) (PE) statistically significant 60 % decrease in CBR statistically significant 60 % decrease in objective responses (ORR) Adding lapatinib to letrozole improve significantly PFS for patients with HR-positive and HER2-positive breast cancer
	palbociclib plus letrozole
	PALOMA-1, 2016 Breast Cancer Res 2016; 18:67-. Lancet Oncol 2015 Jan;16(1):25-35. Breast Cancer Res Treat 2020 Sep;183(2):419-428. NCT00721409	RCT	la/mBC - HR-positive - 1st line (L1)	palbociclib plus letrozole	letrozole	Postmenopausal women with ER-positive and HER2-negative advanced breast cancer. Enrolled in 2 separate cohorts (cohort 1: ER-positive and HER2-negative / cohort 2: they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (also known as INK4A or CDKN2A), or both)	84 / 81	high	suggested	suggested 51 % decrease in progression or deaths (PFS) (PE)
	PALOMA-2, 2016 N Engl J Med 2016; 375:1925-1936-. Breast Cancer Res Treat 2019; 174:719-729-. Clin Breast Cancer 2020; 20:e173-e180-. J Glob Oncol 2019; 5:1-19-. NCT01740427	RCT	la/mBC - HR-positive - 1st line (L1)	palbociclib plus letrozole	placebo plus letrozole	Postmenopausal women with ER-positive, HER2-negative advanced breast cancer were eligible for enrollment if they had not received prior systemic therapy for advanced disease.	444 / 222	NA	conclusif	demonstrated 42 % decrease in progression or deaths (PFS) (PE) suggested 44 % decrease in PFS (extension)
	ribociclib plus letrozole
	MONALEESA-2, 2016 N Engl J Med 2016; 375:1738-1748-. N Engl J Med 2022; 386:942-950-. Ann Oncol 2018; 29:1541-1547-. Breast Cancer Res Treat 2018; 168:127-134-. Breast Cancer Res Treat 2018; 167:659-669-. Clin Breast Cancer 2019; 19:268-277.e1-. NCT01958021	RCT	la/mBC - HR-positive - 1st line (L1)	ribociclib plus letrozole	placebo plus letrozole	Postmenauposal women with locally confirmed HR-positive, HER2-negative recurrent or metastatic BC who had not received previous systematic therapy for advanced disease	334 / 334	low	conclusif	demonstrated 24 % decrease in deaths (OS) (PE) demonstrated 44 % decrease in progression or deaths (PFS) (PE)
versus paclitaxel
	capivasertib plus paclitaxel
	BEECH, 2019 Ann Oncol 2019; 30:774-780-. NCT01625286	RCT	la/mBC - HR-positive - 1st line (L1)	capivasertib plus paclitaxel	placebo plus paclitaxel	patients with ER-positive advanced breast cancer with or without a PIK3CA mutation receiving chemotherapy for the first time in the advanced setting	54 / 56	low	inconclusive	inconclusive 20 % 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)
la/mBC - HR positive - L1 - PIK3CA mutant breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 1st line (L1) la/mBC - HR positive - L1 - PIK3CA mutant
versus paclitaxel
	ipatasertib plus paclitaxel
	IPATunity130, 2022 Breast Cancer Res Treat 2022; 191:565-576-. NCT03337724	RCT	la/mBC - HR positive - L1 - PIK3CA mutant	ipatasertib plus paclitaxel	placebo plus paclitaxel	Patients with HR-positive and HER2-negative PIK3CA/AKT1/PTEN-altered measurable advanced breast cancer	146 / 76	low	inconclusive	inconclusive 0 % increase in progression or deaths (PFS) (PE)
la/mBC - HR-positive - 2nd line (L2) breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 2nd line (L2)
versus chemotherapy
	OBI-822/OBI-821 plus cyclophosphamide
	Huang, 2020 J Immunother Cancer 2020; 8:67-77-. NCT01516307	RCT	la/mBC - HR-positive - 2nd line (L2)	OBI-822/OBI-821 plus cyclophsophamide	cyclophsophamide	Women with MBC achieving SD, partial response (PR), or complete response (CR) after at least one anticancer therapy and with no more than two events of progressive disease after MBC diagnosis. Patients with HR positive were allowed to continue antihormonal therapy with study treatment	225 / 124	NA	inconclusive	inconclusive 4 % decrease in progression or deaths (PFS) (PE)
versus endocrine therapy
	ganitumab plus endocrine therapy
	QUILT-2.015, 2013 Lancet Oncol 2013; 14:228-35-. NCT00626106	RCT	la/mBC - HR-positive - 2nd line (L2)	ganitumumab plus exemestane or fulvetrant	placebo plus exemestane or fulvestrant	postmenopausal women with histologically confirmed HR positive breast cancer and locally advanced or metastatic disease that could not be cured by surgery or radiation. patients from outpatient clinics and hospitals. All patients had HR-positive disease	-/-	low	inconclusive	statistically significant 78 % increase in deaths (OS) inconclusive 17 % increase in progression or deaths (PFS) (PE)
	ribociclib plus endocrine therapy
	MONALEESA-7, 2018 Lancet Oncol 2018; 19:904-915-. Clin Cancer Res 2022; 28:851-859-. N Engl J Med 2019; 381:307-316-. NCT02278120	RCT	la/mBC - HR-positive - 2nd line (L2)	ribociclib plus endocrine therapy plus goserelin	placebo plus endocrine therapy plus goserelin	Women premenopausal or perimenopausal at the time of entry, with histologically or cytologically confirmed HR-positive and HER2-negative breast cancer.	335 / 337	low	conclusif	demonstrated 45 % decrease in progression or deaths (PFS) (PE)
versus exemestane
	entinostat plus exemestane
	E2112, 2021 J Clin Oncol 2021; 39:3171-3181-. NCT02115282	RCT	la/mBC - HR-positive - 2nd line (L2)	entinostat plus exemestane	placebo plus exemestane	Women and men who had histologically confirmed invasive adenocarcinoma of the breast, metastatic or locally advanced and not amenable to local therapy with curative intent	305 / 303	low	inconclusive	inconclusive 1 % decrease in deaths (OS) (PE) inconclusive 13 % decrease in progression or deaths (PFS) (PE)
	ENCORE301, 2013 J Clin Oncol 2013; 31:2128-35-. NCT00676663	RCT	la/mBC - HR-positive - 2nd line (L2)	entinostat plus exemestane	placebo plus exemestane	Postmenopausal women with ER-positive BC who were experiencing disease relapse or progression while receiving an NSAI	64 / 66	NA	suggested	suggested 41 % decrease in deaths (OS) inconclusive 27 % decrease in progression or deaths (PFS) (PE)
	tucidinostat plus exemestane
	ACE, 2019 Lancet Oncol 2019; 20:806-815-. NCT02482753	RCT	la/mBC - HR-positive - 2nd line (L2)	tucidinostat plus exemestane	placebo plus exemestane	Postmenopausal women with HR-positive, HER2-negative, inoperable BC, whose disese relapsed after at least one endocrine therapy.	244 / 121	low	conclusif	demonstrated 25 % decrease in progression or deaths (PFS) (PE)
versus fulvestrant
	abemaciclib plus fulvestrant
	MONARCH 2, 2020 JAMA Oncol 2020; 6:116-124-. Breast Cancer Res 2021; 23:87-. J Clin Oncol 2017 Sep 1;35(25):2875-2884. Oncologist 2020; 25:e243-e251-. NCT02107703	RCT	la/mBC - HR-positive - 2nd line (L2)	abemaciclib plus fulvestrant	placebo plus fulvestrant	Women with HR-positive and HER2-negative advanced breast (ABC) cancer who progressed during neoadjuvant or adjuvantendocrine therapy (ET), within 12months after adjuvant ET, or while receiving first line ET for ABC	446 / 223	low	conclusif	demonstrated 24 % decrease in deaths (OS) (PE) demonstrated 45 % decrease in progression or deaths (PFS) (PE)
	alpelisib plus fulvestrant
	SOLAR-1 (patients with PIK3CA mutant status), 2019 N. Engl. J. Med. 2019; 380:1929-1940 Ann Oncol 2021; 32:208-217-. NCT02437318	RCT	la/mBC - HR-positive - 2nd line (L2)	alpelisib plus fulvestrant	placebo plus fulvestrant	Patients were men and postmenauposal women with locally advanced confirmed HR positive, HER2 negative breast cancer	169 / 172	low	conclusif	inconclusive 14 % decrease in deaths (OS) (PE) demonstrated 35 % decrease in progression or deaths (PFS) (PE)
	SOLAR-1 (patients without PIK3CA mutant status), 2019 N. Engl. J. Med. 2019; 380:1929-1940 Ann Oncol 2021; 32:208-217-. NCT02437318	RCT	la/mBC - HR-positive - 2nd line (L2)	alpelisib plus fulvestrant	placebo plus fulvestrant	Patients were men and postmenauposal women with locally advanced confirmed HR positive, HER2 negative breast cancer / Patient has recurrence or progression of disease during or after AI therapy	115 / 116	low	inconclusive	inconclusive 15 % decrease in progression or deaths (PFS) (PE)
	buparlisib plus fulvestrant
	BELLE-3, 2018 Lancet Oncol 2018; 19:87-100-. NCT01633060	RCT	la/mBC - HR-positive - 2nd line (L2)	buparlisib plus fulvestrant	placebo plus fulvestrant	Postmenopausal women (aged >= 18yr) with HR-positive, HER2-negative, locally advanced or metastatic breast cancer pretreated with aromatase inhibitors and resistant to endocrine therapy for advanced BC.	289 / 143	NA	conclusif	demonstrated 33 % decrease in progression or deaths (PFS) (PE)
	dalpiciclib plus fulvestrant
	DAWNA-1, 2021 Nat Med 2021; 27:1904-1909-. NCT03927456	RCT	la/mBC - HR-positive - 2nd line (L2)	dalpiciclib plus fulvetrant	placebo (matching dulpaciclib) plus fulvestrant	Women aged of 18-75yr with pathologically confirmed HR-positive and HER2-negative locally advanced or metastatic BC. Nor more than 1 previous chemotherapy for advanced disease.	241 / 120	low	conclusif	demonstrated 58 % decrease in progression or deaths (PFS) (PE)
	palbociclib plus fulvestrant
	FLIPPER, 2021 Eur J Cancer 2022; 161:26-37-. NCT02690480	RCT	la/mBC - HR-positive - 2nd line (L2)	palbociclib plus fulvestrant	placebo plus fulvestrant	Postmenauposal women with HR-positive and HER-negative advanced breast cancer	94 / 95	low	suggested	suggested 45 % decrease in progression or deaths (PFS) (PE)
	PALOMA-3, 2016 Oncologist 2021; 26 Suppl 3:S5-S6-. Oncologist 2016; 21:1165-1175-. Lancet Oncol 2016; 17:425-439-. N Engl J Med 2015; 373:209-19-. Oncologist 2017; 22:1028-1038-. N Engl J Med 2018; 379:1926-1936-. Int J Clin Oncol 2019; 24:262-273-. NCT01942135	RCT	la/mBC - HR-positive - 2nd line (L2)	palbociclib plus fulvestrant	placebo plus fulvestrant	Eligible patients were pre- or post menopausal with breast cancer and histologic or cytologicconfirmation of recurrent local or distant disease progression during or within 12 months of completion of adjuvant endocrinetherapy or while receiving or within 1 month after receivingendocrine therapy for MBC	347 / 174	low	conclusif	inconclusive 19 % decrease in deaths (OS) (PE) demonstrated 58 % decrease in progression or deaths (PFS) (PE)
	ribociclib plus fulvestrant
	MONALEESA-3, 2018 J Clin Oncol 2018 Aug 20;36(24):2465-2472. N Engl J Med 2020 Feb 6;382(6):514-524. Ann Oncol 2021 Aug;32(8):1015-1024. NCT02422615	RCT	la/mBC - HR-positive - 2nd line (L2)	ribociclib plus fulvestrant	placebo plus fulvestrant	Postmenopausal women and men with confirmed HR-positive and HER2-negative advanced/metastatic breast cancer	484 / 242	low	conclusif	demonstrated 28 % decrease in deaths (OS) (PE) demonstrated 41 % decrease in progression or deaths (PFS) (PE) suggested 27 % decrease in deaths (OS) (extension)
	sapanisertib plus fulvestrant
	NCT02756364 (sapanisertib daily), 2022 Clin Cancer Res 2022; 28:1107-1116-. NCT02756364	RCT	la/mBC - HR-positive - 2nd line (L2)	sapanasertib plus fulvestrant	fulvestrant	Postmenopausal women with histologic confirmation of ER-positive and HER2-negative metastatic or advanced BC	47 / 46	some concern	inconclusive	inconclusive 23 % decrease in progression or deaths (PFS) (PE)
	NCT02756364 (sapanisertib weekly), 2022 Clin Cancer Res 2022; 28:1107-1116-. NCT02756364	RCT	la/mBC - HR-positive - 2nd line (L2)	sapinasertib plus fulvestrant	fulvestrant	Postmenopausal women with histologic confirmation of ER-positive and HER2-negative metastatic or advanced BC	48 / 46	NA	inconclusive	no statistically significant result
versus paclitaxel
	alisertib plus paclitaxel
	NCT02187991 - HR-positive and HER2-negative cohort, 2021 JAMA Netw Open 2021; 4:e214103-. NCT02187991	RCT	la/mBC - HR-positive - 2nd line (L2)	alisertib plus paclitaxel	paclitaxel	Postemenopausal women (aged >= 18yr) with metastatic or unresectable locally recurrent BC confirmed as ER-positive (HR-positive), ERBB2-negative (HER2-negative) invasive BCor grade 3 TNBC	69 / 70	high	suggested	suggested 44 % decrease in progression or deaths (PFS) (PE)
versus placebo
	metformin
	Pimentel, 2019 Breast 2019; 48:17-23-. NCT01310231	RCT	la/mBC - HR-positive - 2nd line (L2)	metformin plus chemotherapy	placebo plus chemotherapy	Women with metastatic or unresectable locally advanced BC, about to receive 1st to 4th line, any HR or HER2 status	22 / 18	NA	inconclusive	inconclusive 20 % increase in progression or deaths (PFS) (PE) These results do not support the use of metformin with chemotherapy in non-diabetic MBC patients.
la/mBC - HR positive - L2 - all population breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 2nd line (L2) la/mBC - HR positive - L2 - all population
versus fulvestrant
	buparlisib plus fulvestrant
	BELLE-2 (full population), 2017 Lancet Oncol 2017; 18:904-916-. Eur J Cancer 2018; 103:147-154-. NCT01610284	RCT	la/mBC - HR positive - L2 - all population	buparlisib plus fulvestrant	placebo plus fulvestrant	Postmenopausal women (>=18yr), with histollogically confirmed HR-positive and HER2-negative inoperable locally advanced or metastatic breast cancer (with progession on or after aromatase ihnibitor treatment)	576 / 571	low	conclusif	inconclusive 13 % decrease in deaths (OS) (PE) demonstrated 22 % decrease in progression or deaths (PFS) (PE)
la/mBC - HR positive - L2 - PIK3CA mutant breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 2nd line (L2) la/mBC - HR positive - L2 - PIK3CA mutant
versus fulvestrant
	buparlisib plus fulvestrant
	BELLE-2 (PI3K pathway activated), 2017 Lancet Oncol 2017; 18:904-916-. NCT01610284	RCT	la/mBC - HR positive - L2 - PIK3CA mutant	buparlisib plus fulvestrant	placebo plus fulvestrant	Postmenopausal women (>=18yr), with histollogically confirmed HR-positive and HER2-negative inoperable locally advanced or metastatic breast cancer (with progession on or after aromatase ihnibitor treatment). This subgroup population included only patients with PI3K pathway activated	188 / 184	low	suggested	suggested 24 % decrease in progression or deaths (PFS) (PE)
es-BC - TNBC - NA - all population breast cancer - triple negative es-BC - Triple negatif (TNBC) - (neo)adjuvant (NA) es-BC - TNBC - NA - all population
versus carboplatin plus nab-paclitaxel
	atezolizumab plus carboplatin plus nab-paclitaxel
	NeoTRIPaPDLA unpublished Ann Oncol 2022; 33:534-543-. NCT02620280	RCT	es-BC - TNBC - NA - all population	atezolizumab plus carboplatine plus nab-paclitaxel	carboplatine plus nab-paclitaxel	Neoadjuvant Therapy in TRIPle Negative Breast Cancer (early or locally advanced)	88 / 86	NA	inconclusive	no statistically significant result
versus placebo
	durvalumab alone
	GeparNuevo, 2019 Ann. Oncol. 2019; : NCT02685059	RCT	es-BC - TNBC - NA - all population	durvalumab followed by nab-paclitaxel	placebo followed by nab-paclitaxel	Patients with previously untreated uni- or bilateral primary, non-metastatic invasive TNBC with a tumour of at least 2 cm (cT2-cT4a-d) treated as neoadjuvant	88 / 86	some concern	suggested	suggested 76 % decrease in deaths (OS) (extension) inconclusive 45 % increase in pCR (PE)
	olaparib
	OlympiA (BIG 6-13, NSABP B-55) unpublished New England Journal of Medicine NCT02032823	RCT	es-BC - TNBC - NA - all population	olaparib	placebo	patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors	921 / 915	NA	conclusif	demonstrated 32 % decrease in deaths (OS) (PE) demonstrated 42 % decrease in iDFS (PE)
	pembrolizumab alone
	KEYNOTE-522, 2020 N. Engl. J. Med. 2020; 382:810-821 N Engl J Med 2022; 386:556-567-. NCT03036488	RCT	es-BC - TNBC - NA - all population	pembrolizumab	placebo	previously previously untreated, nonmetastatic disease, stage II or stage III, triple-negative breast cancer treated with paclitaxel and carboplatin, treated for neoadjuvant phase and an adjuvant phase;	784 / 390	low	conclusif	demonstrated 12.6-fold increase in pCR (PE) suggested 37 % decrease in events or deaths (EFS) (PE)
versus placebo plus SoC
	atezolizumab plus nab-paclitxel followed by doxorubicin plus cyclophosphamide
	IMpassion-031 (all population), 2020 Lancet 2020 Oct 10;396(10257):1090-1100. NCT03197935	RCT	es-BC - TNBC - NA - all population	Atezolizumab plus nab-paclitaxel followed by doxorubicin and cyclophosphamide with filgrastim or pegfilgrastim support	placebo plus nab-paclitaxel followed by doxorubicin and cyclophosphamide with filgrastim or pegfilgrastim support	neoadjuvant setting in participants with early stage (stage II-III) triple negative breast cancer	165 / 168	low	conclusif	demonstrated 95 % increase in pCR (PE)
es-BC - TNBC - NA - PDL1 positive breast cancer - triple negative es-BC - Triple negatif (TNBC) - (neo)adjuvant (NA) es-BC - TNBC - NA - PDL1 positive
versus placebo plus SoC
	atezolizumab plus nab-paclitxel followed by doxorubicin plus cyclophosphamide
	IMpassion-031 (PDL1>1%), 2020 Lancet 2020 Oct 10;396(10257):1090-1100. NCT03197935	RCT	es-BC - TNBC - NA - PDL1 positive	Atezolizumab plus nab-paclitaxel followed by doxorubicin and cyclophosphamide with filgrastim or pegfilgrastim support	placebo plus nab-paclitaxel followed by doxorubicin and cyclophosphamide with filgrastim or pegfilgrastim support	neoadjuvant setting in participants with early stage (stage II III) triple negative breast cancer with PDL1 >1%	78 / 76	low	suggested	suggested 1.2-fold increase in pCR (PE)
mBC - Triple negative (TNBC) - 1st Line (L1) breast cancer - triple negative mBC - Triple negative (TNBC) - 1st Line (L1)
versus Standard of Care (SoC)
	capivasertib plus paclitaxel
	PAKT (PIK3CA/AKT1/PTEN-altered), 2020 J Clin Oncol 2020; 38:423-433-. NCT02423603	RCT	mBC - Triple negative (TNBC) - 1st Line (L1)	capiversatib plus paclitaxel	placebo plus paclitaxel	Patients had histologically confirmed, metastatic or locally advanced TNBC not amenable to curative resection. Previous systemic therapy for locally advanced or metastatic disease was not permitted, but previous adjuvant or neoadjuvant chemotherapy was allowed.	17 / 11	NA	suggested	suggested 70 % decrease in progression or deaths (PFS)
mBC - TNBC - L1 - all population breast cancer - triple negative mBC - Triple negative (TNBC) - 1st Line (L1) mBC - TNBC - L1 - all population
versus placebo plus SoC
	pembrolizumab plus SoC
	KEYNOTE-355 (all population), 2020 Lancet 2020 Dec 5;396(10265):1817-1828. ESMO Congres 2021 N Engl J Med 2022 Jul 21;387(3):217-226. NCT02819518	RCT	mBC - TNBC - L1 - all population	Pembrolizumab plus chemotherapy	placebo plus chemotherapy	patients with with untreated locally recurrent inoperable or metastatic triple-negative breast cancer (all population)	566 / 281	low	inconclusive	inconclusive 11 % decrease in deaths (OS) (PE) suggested 18 % decrease in progression or deaths (PFS) (PE) statistically significant 76 % decrease in objective responses (ORR) OS results from ESMO Congres 2021
versus Standard of Care (SoC)
	atezolizumab plus nab-paclitaxel
	IMpassion-130 (all population), 2018 Lancet Oncol. 2020; 21:44-59 N. Engl. J. Med. 2018; 379:2108-2121 Jpn. J. Clin. Oncol. 2019; 49:1083-1091 Ann. Oncol. 2020; : Ann Oncol 2021 Aug;32(8):983-993. NCT02425891	RCT	mBC - TNBC - L1 - all population	atezolizumab plus nab-paclitaxel	placebo plus nab-paclitaxel	patients with untreated metastatic triple-negative breast cancer (TNBC) treated with nab-paclitaxel	451 / 451	low	conclusif	inconclusive 14 % decrease in deaths (OS) (PE) demonstrated 20 % decrease in progression or deaths (PFS) (PE) suggested 20 % decrease in PFS (extension)
	atezolizumab plus paclitaxel
	IMpassion-131 (all population), 2020 Ann Oncol 2021; 32:994-1004-. NCT03125902	RCT	mBC - TNBC - L1 - all population	Atezolizumab plus paclitaxel	placebo plus paclitaxel	Patients had metastatic or unresectable locally advanced measurable TNBC, had received no prior chemotherapy or targeted therapy for aTNBC and had completed any prior (neo)adjuvant chemotherapy for early breast cancer 12 months before being randomised to the trial.	431 / 220	NA	inconclusive	inconclusive 14 % decrease in progression or deaths (PFS),progression or deaths (PFS) (PE) Atezolizumab (Tecentriq) in combination with paclitaxel did not demonstrate a statistically significant improvement in progression-free survival (PFS) as a first-line treatment for patients with PD-L1–positive triple-negative breast cancer (TNBC) / qualitative results only NO ROB
	capivasertib plus paclitaxel
	PAKT (all population), 2020 J Clin Oncol 2020; 38:423-433-. NCT02423603	RCT	mBC - TNBC - L1 - all population	capiversatib plus paclitaxel	placebo plus paclitaxel	Patients had histologically confirmed, metastatic or locally advanced TNBC not amenable to curative resection. Previous systemic therapy for locally advanced or metastatic disease was not permitted, but previous adjuvant or neoadjuvant chemotherapy was allowed.	70 / 70	NA	suggested	suggested 39 % decrease in deaths (OS) inconclusive 26 % decrease in progression or deaths (PFS) (PE)
	ipatasertib plus paclitaxel
	LOTUS, 2017 Lancet Oncol 2017; 18:1360-1372-. Breast Cancer Res Treat 2021; 189:377-386-. NCT02162719	RCT	mBC - TNBC - L1 - all population	ipatasertib plus paclitaxel	placebo plus paclitaxel	Women with locally advanced or metastatic TNBC not amenable to curative resection. Previous systemic therapy for locally advanced or metastatic disease was not permitted. Previous (neo)adjuvant treatment completed at least 6 months before the first dose was allowed	62 / 62	NA	suggested	suggested 40 % decrease in progression or deaths (PFS) (PE)
	veliparib plus paclitaxel plus carboplatin
	BrighTNess (velaparib-P-C (arm A) vs paclitaxel - carboplatin (arm B)), 2018 Lancet Oncol 2018; 19:497-509-. NCT02032277	RCT	mBC - TNBC - L1 - all population	veliparib plus paclitaxel plus carboplatin	placebo plus paclitaxel plus carboplatin	Patients: women who had histologically or cytologically confirmed invasive TNBC, clinical stage II-III	316 / 160	NA	inconclusive	inconclusive 12 % increase in events or deaths (EFS) (PE) inconclusive 25 % increase in events or deaths (EFS) (PE) inconclusive 16 % decrease in pCR (PE)
	BrighTNess (velaparib-P-C (arm A) vs paclitaxel alone (arm C)), 2018 Lancet Oncol 2018; 19:497-509-. NCT02032277	RCT	mBC - TNBC - L1 - all population	veliparib plus paclitaxel plus carboplatin	placebo matching veliparib plus placebo matching carboplatin plus paclitaxel	Patients: women who had histologically or cytologically confirmed invasive TNBC, clinical stage II-III	316 / 158	NA	conclusif	inconclusive 18 % decrease in deaths (OS) (PE) demonstrated 1.5-fold increase in pCR (PE) suggested 37 % decrease in events or deaths (EFS) (PE)
mBC - TNBC - L1 - PDL1 positive breast cancer - triple negative mBC - Triple negative (TNBC) - 1st Line (L1) mBC - TNBC - L1 - PDL1 positive
versus placebo plus SoC
	pembrolizumab plus SoC
	KEYNOTE-355 (CPS>10), 2020 Lancet 2020 Dec 5;396(10265):1817-1828. ESMO Congres 2021 NCT02819518	RCT	mBC - TNBC - L1 - PDL1 positive	Pembrolizumab plus chemotherapy	placebo plus chemotherapy	patients with with untreated locally recurrent inoperable or metastatic triple-negative breast cancer (PDL1 CPS>10)	220 / 103	low	conclusif	demonstrated 27 % decrease in deaths (OS) (PE) demonstrated 34 % decrease in progression or deaths (PFS) (PE) OS results from ESMO Congres 2021
	KEYNOTE-355 (CPS>1), 2020 Lancet 2020 Dec 5;396(10265):1817-1828. ESMO Congres 2021 NCT02819518	RCT	mBC - TNBC - L1 - PDL1 positive	Pembrolizumab plus chemotherapy	placebo plus chemotherapy	patients with with untreated locally recurrent inoperable or metastatic triple-negative breast cancer (PDL1 CPS>1)	425 / 211	low	suggested	inconclusive 14 % decrease in deaths (OS) (PE) suggested 25 % decrease in progression or deaths (PFS) (PE) OS results from ESMO Congres 2021
versus Standard of Care (SoC)
	atezolizumab plus nab-paclitaxel
	IMpassion-130 (PDL1>1%), 2018 Lancet Oncol. 2020; 21:44-59 N. Engl. J. Med. 2018; 379:2108-2121 Jpn. J. Clin. Oncol. 2019; 49:1083-1091 Ann. Oncol. 2020; : Ann Oncol 2021 Aug;32(8):983-993. NCT02425891	RCT	mBC - TNBC - L1 - PDL1 positive	atezolizumab plus nab-paclitaxel	placebo plus nab-paclitaxel	patients with untreated metastatic triple-negative breast cancer treated with nab-paclitaxel, and PDL1 positive population (>1%)	185 / 184	low	conclusif	suggested 29 % decrease in deaths (OS) (PE) demonstrated 38 % decrease in progression or deaths (PFS) (PE) suggested 37 % decrease in PFS (extension)
	atezolizumab plus paclitaxel
	IMpassion-131 (PD-L1 > 1%), 2020 Ann Oncol 2021; 32:994-1004-. NCT03125902	RCT	mBC - TNBC - L1 - PDL1 positive	Atezolizumab plus paclitaxel	placebo plus paclitaxel	Patients had metastatic or unresectable locally advanced measurable TNBC, had received no prior chemotherapy or targeted therapy for aTNBC and had completed any prior (neo)adjuvant chemotherapy for early breast cancer 12 months before being randomised to the trial.	191 / 101	NA	inconclusive	inconclusive 18 % decrease in progression or deaths (PFS),progression or deaths (PFS) (PE)
mBC-Triple negative (TNBC) - 2nd Line (L2) breast cancer - triple negative mBC-Triple negative (TNBC) - 2nd Line (L2)
versus Standard of Care (SoC)
	sacituzumab govitecan
	ASCENT (patients without brain metastases), 2021 New England Journal of Medicine NCT02574455	RCT	mBC-Triple negative (TNBC) - 2nd Line (L2)	Sacituzumab govitecan	single agent chemotheraopy² of the physician's choice (eribulin, vinorelbine, capecitabine or gemcitabine)	Patients with metastatic triple-negative breast cancer that was relapsed or refractory to two or more previous standard chemotherapy regimens for unresectable, locally andvanced or metastatic disease (previous thearapy had to include taxanes).	235 / 233	NA	suggested	suggested 52 % decrease in deaths (OS) (PE) suggested 59 % decrease in progression or deaths (PFS) (PE)
	ASCENT (all population), 2021 New England Journal of Medicine NCT02574455	RCT	mBC-Triple negative (TNBC) - 2nd Line (L2)	Sacituzumab govitecan	single agent chemotheraopy of the physician's choice (eribulin, vinorelbine, capecitabine or gemcitabine)	Patients with metastatic triple-negative breast cancer that was relapsed or refractory to two or more previous standard chemotherapy regimens for unresectable, locally andvanced or metastatic disease (previous thearapy had to include taxanes).	267 / 262	NA	suggested	suggested 49 % decrease in deaths (OS) (PE) suggested 57 % decrease in progression or deaths (PFS) (PE)
	talazoparib
	EMBRACA, 2018 Annals of Oncology NCT01945775	RCT	mBC-Triple negative (TNBC) - 2nd Line (L2)	talazoparib	chemotherapy	Patients with HER2-negative locally advanced or metastatic breast cancer and a deleterious or suspected deleterious gBRCA1/2 mutation. Patients had received 3 or less previous cytotoxic regimens for advanced disease and previous treatment with a taxane, an anthracycline, or both (unless contraindicated).	287 / 144	NA	conclusif	inconclusive 15 % decrease in deaths (OS) (PE) demonstrated 46 % decrease in progression or deaths (PFS) (PE) demonstrated 4.0-fold increase in objective responses (ORR) (PE)
mBC - TNBC - L2 - all population breast cancer - triple negative mBC-Triple negative (TNBC) - 2nd Line (L2) mBC - TNBC - L2 - all population
versus Standard of Care (SoC)
	olaparib
	OlympiAD, 2017 N Engl J Med 2017 Aug 10;377(6):523-533. Ann Oncol 2019 Apr 1;30(4):558-566. NCT02000622	RCT	mBC - TNBC - L2 - all population	olaparib	standard chemotherapy	Patients with HER-2 negative metastatic breast cancer that was HR positive or triple negative. Patients had a confirmed deleterious or suspected deleterious germline BRCA mutation and had receive no more than 2 previous chemotherapy regimens for metastatic disease.	205 / 97	NA	conclusif	inconclusive 10 % decrease in deaths (OS) (PE) demonstrated 42 % decrease in progression or deaths (PFS) (PE)
	pembrolizumab alone
	KEYNOTE-119 (all population), 2019 Annals of Oncology, Elsevier Lancet Oncol 2021 Apr;22(4):499-511. NCT02555657	RCT	mBC - TNBC - L2 - all population	Pembrolizumab	chemotherapy (single agent)	patients with previously treated metastatic triple negative breast cancer (mTNBC)	312 / 310	some concern	inconclusive	inconclusive 3 % decrease in deaths (OS),deaths (OS) (PE) statistically significant 60 % increase in progression or deaths (PFS),progression or deaths (PFS) statistically significant 40 % decrease in DCR,DCR
mBC - TNBC - L2 - PDL1 positive breast cancer - triple negative mBC-Triple negative (TNBC) - 2nd Line (L2) mBC - TNBC - L2 - PDL1 positive
versus Standard of Care (SoC)
	pembrolizumab alone
	KEYNOTE-119 (PDL1 CPS>10), 2019 Annals of Oncology, Elsevier Lancet Oncol 2021 Apr;22(4):499-511. NCT02555657	RCT	mBC - TNBC - L2 - PDL1 positive	Pembrolizumab	chemotherapy (single agent)	patients with previously treated metastatic triple negative breast cancer (mTNBC) patients with PDL1 CPS> 10 only	96 / 98	some concern	inconclusive	inconclusive 22 % decrease in deaths (OS),deaths (OS) (PE)
	KEYNOTE-119 (PDL1 CPS>1), 2019 Annals of Oncology, Elsevier Lancet Oncol 2021 Apr;22(4):499-511. NCT02555657	RCT	mBC - TNBC - L2 - PDL1 positive	Pembrolizumab	chemotherapy (single agent)	patients with previously treated metastatic triple negative breast cancer (mTNBC) patients with PDL1 CPS> 1 only	203 / 202	some concern	inconclusive	inconclusive 14 % decrease in deaths (OS),deaths (OS) (PE) statistically significant 35 % increase in progression or deaths (PFS),progression or deaths (PFS)
metastatic/advanced - breast cancer (mBC) metastatic/advanced - breast cancer (mBC)
versus chemotherapy
	trastuzumab deruxtecan
	DESTINY-Breast04, 2022 New England Journal of Medicine NCT03734029	RCT	metastatic/advanced - breast cancer (mBC)	trastuzumab deruxtecan	physician’s choice of chemotherapy	patients with HER2-low metastatic breast cancer who had received one or two previous lines of chemotherapy	373 / 184	some concern	conclusif	demonstrated 36 % decrease in deaths (OS) (PE) demonstrated 50 % decrease in progression or deaths (PFS) (PE)

breast cancer (BC) breast cancer (BC)

breast cancer - adjuvant breast cancer - adjuvant

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

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)

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

es-BC - HR-positive - 1st line (L1) breast cancer - HR positive es-BC - HR-positive - 1st line (L1)

la/mBC - HR positive breast cancer - HR positive la/mBC - HR positive

la/mBC - HR positive - (neo)adjuvant (NA) breast cancer - HR positive la/mBC - HR positive la/mBC - HR positive - (neo)adjuvant (NA)

la/mBC - HR-positive - 1st line (L1) breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 1st line (L1)

la/mBC - HR positive - L1 - PIK3CA mutant breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 1st line (L1) la/mBC - HR positive - L1 - PIK3CA mutant

la/mBC - HR-positive - 2nd line (L2) breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 2nd line (L2)

la/mBC - HR positive - L2 - all population breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 2nd line (L2) la/mBC - HR positive - L2 - all population

la/mBC - HR positive - L2 - PIK3CA mutant breast cancer - HR positive la/mBC - HR positive la/mBC - HR-positive - 2nd line (L2) la/mBC - HR positive - L2 - PIK3CA mutant

es-BC - TNBC - NA - all population breast cancer - triple negative es-BC - Triple negatif (TNBC) - (neo)adjuvant (NA) es-BC - TNBC - NA - all population

es-BC - TNBC - NA - PDL1 positive breast cancer - triple negative es-BC - Triple negatif (TNBC) - (neo)adjuvant (NA) es-BC - TNBC - NA - PDL1 positive

mBC - Triple negative (TNBC) - 1st Line (L1) breast cancer - triple negative mBC - Triple negative (TNBC) - 1st Line (L1)

mBC - TNBC - L1 - all population breast cancer - triple negative mBC - Triple negative (TNBC) - 1st Line (L1) mBC - TNBC - L1 - all population

mBC - TNBC - L1 - PDL1 positive breast cancer - triple negative mBC - Triple negative (TNBC) - 1st Line (L1) mBC - TNBC - L1 - PDL1 positive

mBC-Triple negative (TNBC) - 2nd Line (L2) breast cancer - triple negative mBC-Triple negative (TNBC) - 2nd Line (L2)