metaEvidence - study list


	Study	study type RCT OBS RCT + OBS	Pathology	T1	T0	Patients	sample sizes	ROB	Results
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 eribulin
	eribulin, pembrolizumab alone
	NCT03051659, 2020 JAMA Oncol 2020; 6:1598-1605-. Nat Commun 2021; 12:5563-. NCT03051659	RCT	la/mBC - HR positive	eribulin mesylate plus pembrolizumab	eribulin mesylate monotherapy	Patients must have histologically or cytologically confirmed Stage IV invasive breast cancer, must have HR positive, HER2-negative breast cancer (ER>1% and/or, PR>1%, HER2-negative, must have already received or been intolerant to at least two lines of hormonal therapies (including the adjuvant or metastatic setting) or be appropriate candidates for chemotherapy,	44 / 44	NA	inconclusive	inconclusive 20 % decrease in progression or deaths (PFS),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 (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)
	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)
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)
versus pegylated liposomal doxorubicin and cyclophosphamide
	nivolumab plus ipilimumab, pegylated liposomal doxorubicin and cyclophosphamide
	ICON, 2024 J Immunother Cancer 2024; 12:1240-1247-. J Transl Med 2020; 18:269-. NCT03409198	RCT	la/mBC - HR positive - L2 - all population	Ipilimumab plus nivolumab plus PLD plus cyclophosphamide	PLD plus cyclophosphamide	Patients with HR mBC starting first-/second- line chemotherapy (chemo)	49 / 33	some concern	inconclusive	inconclusive 6 % decrease in progression or deaths (PFS),progression or deaths (PFS) (PE) The addition of ipi/nivo to chemotherapy increased toxicity without improving efficacy. Ipi/nivo administered sequentially to chemotherapy was tolerable and induced clinical responses.
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)

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