Treatment challenges for community oncologists treating postmenopausal women with endocrine-resistant, hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer

Figures & data

Table 1 Overview of clinical trials in patients with endocrine-resistant breast cancer

Agent	Phase of development	Clinical trial identifier	Status	Details
PI3K/Akt/mTOR inhibitors
Alpelisib (BYL719)	I	NCT02077933	Recruiting	Safety and efficacy of alpelisib + everolimus or alpelisib + everolimus + exemestane in patients with advanced breast cancer, renal cell cancer, and pancreatic tumors
	III	NCT02437318	Recruiting	Alpelisib + fulvestrant versus placebo + fulvestrant in patients with HR+, HER2− advanced breast cancer who progressed on or after aromatase inhibitor therapy
Buparlisib (BKM120)	III	NCT01610284 (BELLE-2)	Completed	BKM120 + fulvestrant versu placebo + fulvestrant in postmenopausal women with HR+, HER2− locally advanced or metastatic breast cancer refractory to aromatase inhibitors
	III	NCT01633060 (BELLE-3)	Recruiting	BKM120 + fulvestrant versus placebo + fulvestrant in postmenopausal women with HR+, HER2− aromatase- inhibitor treated locally advanced or metastatic breast cancer in patients who progressed on or after mTOR inhibitor treatment
Taselisib	III	NCT02340221 (SANDPIPER)	Recruiting	Taselisib + fulvestrant versus placebo + fulvestrant in postmenopausal women with HR+, HER2− locally advanced or metastatic breast cancer who have disease recurrence or progression during or after aromatase inhibitor therapy
HDAC inhibitors
Entinostat	III	NCT02115282	Recruiting	Exemestane + entinostat versus exemestane + placebo in postmenopausal women and men with recurrent HR+, HER2− locally advanced or metastatic breast cancer with disease progression on NSAI therapy in the metastatic setting or relapse while on or within 12 months of completing NSAI therapy
CDK inhibitors
Palbociclib (PD-0332991)	III	NCT01740427 (PALOMA-2)	Ongoing	Palbociclib + letrozole versus placebo + letrozole for first-line treatment of postmenopausal women with ER+, HER2− advanced breast cancer
	III	NCT01942135 (PALOMA-3)	Completed	Palbociclib + fulvestrant versus placebo + fulvestrant in women of any menopausal status with HR+, HER2− metastatic breast cancer after endocrine failure
	III	NCT02028507 (PEARL)	Recruiting	Palbociclib + exemestane versus capecitabine in HR+, HER2− metastatic breast cancer in postmenopausal women with resistance to NSAIs
Ribociclib (LEE011)	III	NCT01958021	Recruiting	Ribociclib + letrozole versus placebo + letrozole as first- line therapy of HR+, HER2− advanced breast cancer in postmenopausal women
	II	NCT01919229	Completed	Ribociclib (400 mg) + letrozole versus LEE011 (600 mg) + letrozole in HR+, HER2−, grades 2–3 invasive breast cancer in postmenopausal women
	I/II	NCT01857193	Recruiting	Ribociclib + everolimus + exemestane versus LEE011 + exemestane versus everolimus + exemestane in patients with ER+, HER2− advanced breast cancer
	III	NCT02422615	Recruiting	Ribociclib (600 mg) + fulvestrant versus placebo + fulvestrant in HR+/HER2− advanced breast cancer who have received no or only one line of prior endocrine treatment
Abemaciclib (LY2835219)	III	NCT02246621 (MONARCH 3)	Ongoing	Abemaciclib (300 mg) + letrozole or anastrozole versus placebo + letrozole or anastrozole in HR+, HER2− locally recurrent or metastatic breast cancer with no prior systemic therapy
	III	NCT02107703 (MONARCH 2)	Ongoing	Abemaciclib (300 mg) + fulvestrant versus placebo + fulvestrant in HR+, HER2− locally advanced or metastatic breast cancer
Src-kinase pathway inhibitors
Dasatinib	II	NCT00696072	Completed	Letrozole + dasatinib versus letrozole as first- and second-line treatment for HR+, HER2− postmenopausal patients with unresectable, locally recurrent or metastatic breast cancer
	II	NCT00754325		Fulvestrant with or without dasatinib in men and postmenopausal women who have hormone receptor- positive advanced breast cancer previously treated with an aromatase inhibitor
NF-κB pathway and proteasome inhibitors
Bortezomib	II	NCT01142401	Ongoing	Fulvestrant + bortezomib versus fulvestrant in postmenopausal women with ER+ locally advanced or metastatic breast cancer resistant to aromatase inhibitors
EGFR inhibitors
Erlotinib	II	NCT00570258	Ongoing	Fulvestrant + erlotinib versus fulvestrant + placebo in postmenopausal women with HR+ metastatic breast cancer who progressed on first-line hormonal therapy
Vandetanib	II	NCT00811369 (ZAMBONEY)	Completed (no study results reported)	Fulvestrant + vandetanib versus fulvestrant + placebo in postmenopausal women with bone predominant, HR+ metastatic breast cancer

Abbreviations: CDK, cyclin-dependent kinase; EGFR, epidermal growth factor receptor; ER+, estrogen receptor-positive; HDAC, histone deacetylase; HER2−, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; mTOR, mammalian target of rapamycin; NSAI, nonsteroidal aromatase inhibitor.