Clinical trial NCT02422615: Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer.
Official title: A Randomized Double-blind, Placebo-controlled Study of Ribociclib in Combination With Fulvestrant for the Treatment of Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer Who Have Received no or Only One Line of Prior Endocrine Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced Breast Cancer
Keywords: HR-positive
HER2-negative
Advanced breast cancer
LEE011
ribociclib
fulvestrant
faslodex
CDK
CDK4
CDK6
CDK4/6
CDK4/6 inhibitor
Phase III
ER-positive
PR-positive
Postmenopausal
Men
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Use
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-04-21
Enrollment: 726
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Following protocol amendment 4 (29-Jan-2020), study participants were unblinded, with an opportunity for those patients still in the study in the arm of placebo + fulvestrant to transition to the treatment of ribociclib + fulvestrant.
Primary purpose: TREATMENT

Brief summary: The main aim of this study was to evaluate the efficacy and safety of adding ribociclib to fulvestrant in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer.

Detailed description: This study was a randomized, phase III, double-blind, placebo-controlled international trial aimed at determining the efficacy and safety of treatment with fulvestrant in combination with ribociclib compared to fulvestrant with placebo in men and postmenopausal women diagnosed with HR+, HER2-negative advanced breast cancer. The study comprised four phases: screening (up to 28 days), randomized treatment, post-treatment disease progression follow-up, and post-treatment survival follow-up.

Enrolled participants were randomly assigned to receive either fulvestrant+ribociclib or fulvestrant+placebo in a ratio of 2:1. The randomization process was stratified based on the presence of liver and/or lung metastases (yes versus no) and prior endocrine therapy. Treatment was administered until disease progression, occurrence of unacceptable toxicity, or discontinuation from the study treatment for other reasons.

Participants who discontinued treatment due to reasons other than disease progression or withdrawal of consent for efficacy follow-up continued to be monitored until disease progression, death, withdrawal of consent, loss to follow-up, or subject/guardian decision.

All participants who discontinued treatment were followed for survival until the predetermined number of overall survival (OS) events was reached.

A protocol amendment 4 (dated 29-Jan-2020) allowed for unblinding of study participants, and those still receiving placebo had the option to switch to the ribociclib arm. The decision for crossover was made at the investigator's discretion and required patient consent.

Eligibility criteria: Key Inclusion Criteria:

1. Patients were adults, both male and female, aged ≥ 18 years at the time of providing informed consent. Female patients were required to be postmenopausal. Informed consent was obtained prior to any trial-related activities, following local guidelines.
2. Patients had a confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer, determined through histological and/or cytological examination by a local laboratory. Patients also had HER2-negative breast cancer.
3. Patients had either measurable disease as per RECIST 1.1 criteria or at least one predominantly lytic bone lesion.
4. Patients had advanced breast cancer, which included locoregionally recurrent disease not amenable to curative therapies (such as surgery or radiotherapy) or metastatic breast cancer. Patients fell into one of the following categories:

   * Newly diagnosed with advanced/metastatic breast cancer and treatment-naïve.
   * Relapsed with documented evidence of relapse more than 12 months after completing (neo)adjuvant endocrine therapy, without any prior treatment for advanced/metastatic disease.
   * Relapsed with documented evidence of relapse on or within 12 months from completing (neo)adjuvant endocrine therapy, without any prior treatment for advanced/metastatic disease.
   * Relapsed with documented evidence of relapse more than 12 months after completing adjuvant endocrine therapy and subsequently progressed after receiving one line of endocrine therapy (antiestrogen or aromatase inhibitor) for advanced/metastatic disease.
   * Newly diagnosed with advanced/metastatic breast cancer at diagnosis and progressed after receiving one line of endocrine therapy (antiestrogen or aromatase inhibitor), with documented evidence of progression.
5. Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Patients had adequate bone marrow and organ function.

Key Exclusion Criteria:

Patients with symptomatic visceral disease or disease burden that rendered them ineligible for endocrine therapy, based on the investigator's judgment.

2. Patients who had received prior treatment with chemotherapy (except for neoadjuvant/adjuvant chemotherapy), fulvestrant, or any CDK4/6 inhibitor.

3. Patients with inflammatory breast cancer at the screening stage. 4. Patients with central nervous system (CNS) involvement, unless they were at least 4 weeks from completing prior therapy before initiating the study treatment and had a stable CNS tumor at the time of screening. They were also required not to be receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases.

5. Patients with clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.

6. Patients who were currently receiving any of the following substances, which could not be discontinued 7 days prior to initiating treatment:

* Known strong inducers or inhibitors of CYP3A4/5.
* Substances with a known risk of prolonging the QT interval or inducing Torsades de Pointes.
* Substances with a narrow therapeutic window and predominantly metabolized through CYP3A4/5.
* Herbal preparations/medications, dietary supplements.

Primary outcomes:
measure: Progression Free Survival (PFS) Per Investigator Assessment
timeFrame: From randomization to first documented progression or death, assessed up to approximately 26 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to death, assessed up to approximately 46 months
measure: Progression Free Survival (PFS) Per Blinded Independent Review Committee (BIRC)
timeFrame: From randomization to first documented progression or death, assessed up to approximately 26 months
measure: Overall Response Rate (ORR) Per Investigator Assessment
timeFrame: Up to approximately 26 months
measure: Clinical Benefit Rate (CBR) Per Investigator Assessment
timeFrame: Up to approximately 26 months
measure: Time to Response (TTR) Per Investigator Assessment
timeFrame: From randomization to first response, assessed up to approximately 26 months
measure: Duration of Response (DOR) Per Investigator Assessment
timeFrame: From first documented response to progression or death, assessed up to approximately 26 months
measure: Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) in One Score Category
timeFrame: Up to approximately 26 months
measure: Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (GHS/QoL) Scale Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
timeFrame: Up to approximately 26 months
measure: Change From Baseline in the GHS/QoL Scale Score of the EORTC QLQ-C30
timeFrame: Baseline, every 8 weeks after randomization during 18 months, then every 12 weeks up to end of treatment; end of treatment; and every 8 or 12 weeks post-treatment until progression (post-treatment efficacy visits), assessed up to approximately 26 months
measure: Ribociclib Plasma Concentrations
timeFrame: Cycle 1 and Cycle 2 at Day 15 pre-dose and at 2, 4, and 6 hours post-dose. Cycle=28 days
measure: LEQ803 Plasma Concentrations
timeFrame: Cycle 1 and Cycle 2 at Day 15 pre-dose and at 2, 4, and 6 hours post-dose. Cycle = 28 days
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Southern Cancer Center PC SC-2
state: Alabama
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers SC-2
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group .
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA Medical Center .
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation SC
state: California
city: Santa Rosa
country: United States
facility: St Joseph Heritage Healthcare
state: California
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Davie
country: United States
facility: Florida Cancer Research Institute Dept of Oncology
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute SC
state: Florida
city: Orlando
country: United States
facility: UF Health Cancer Center at Orlando Health
state: Florida
city: Thomasville
country: United States
facility: John D Archbold Memorial Hospital Main
state: Georgia
city: Honolulu
country: United States
facility: Moanalua Medical Center. Attn: Oncology Dept SC
state: Hawaii
city: Park Ridge
country: United States
facility: Oncology Specialists, SC Advocate Medical Group-Niles
state: Illinois
city: Jackson
country: United States
facility: Jackson Oncology Associates SC
state: Mississippi
city: Neptune
country: United States
facility: Meridian Health Systems Regulatory
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center SC
state: New Mexico
city: Glens Falls
country: United States
facility: CR Wood Cancer Center SC
state: New York
city: Lake Success
country: United States
facility: Clinical Research Alliance .
state: New York
city: New York
country: United States
facility: NYU Langone Med Center CV Research NYU Langone Medical Center
state: New York
city: Zanesville
country: United States
facility: Genesis Cancer Services SC
state: Ohio
city: Hershey
country: United States
facility: Penn State University Milton S Hershey Medical Center SC
state: Pennsylvania
city: Houston
country: United States
facility: Millennium Research Clin Develop SC
state: Texas
city: Ogden
country: United States
facility: Northern Utah Cancer Associates CFTY720DUS01
state: Utah
city: Everett
country: United States
facility: Providence Regional Cancer Partnership .
state: Washington
city: Lacey
country: United States
facility: Providence Regional Cancer System SC
state: Washington
city: Seattle
country: United States
facility: Virginia Mason Medical Center-Oncology SC
state: Washington
city: St Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Herston
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: East Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
state: Tyrol
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Aalst
country: Belgium
facility: Novartis Investigative Site
city: Charleroi
country: Belgium
facility: Novartis Investigative Site
city: Hasselt
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Namur
country: Belgium
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Surrey
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Victoria
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Moncton
country: Canada
facility: Novartis Investigative Site
state: New Brunswick
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Brampton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Kingston
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Newmarket
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Rimouski
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Trois Rivieres
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Monteria
country: Colombia
facility: Novartis Investigative Site
city: Brno Bohunice
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Liberec
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Prague 8
country: Czechia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Aarhus
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Vejle
country: Denmark
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
state: Cedex
city: Saint-Cloud
country: France
facility: Novartis Investigative Site
state: Hauts De Seine
city: Reims
country: France
facility: Novartis Investigative Site
state: Marne
city: Besancon Cedex
country: France
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Brest
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Le Mans Cedex
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Limoges
country: France
facility: Novartis Investigative Site
city: Paris 13
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Toulon La Seyne Sur Mer
country: France
facility: Novartis Investigative Site
city: Langen
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Georgsmarienhuette
country: Germany
facility: Novartis Investigative Site
state: Lower Saxony
city: Augsburg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bielefeld
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Fuerth
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Luebeck
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Mühlhausen
country: Germany
facility: Novartis Investigative Site
city: Oldenburg
country: Germany
facility: Novartis Investigative Site
city: Ravensburg
country: Germany
facility: Novartis Investigative Site
city: Saarbruecken
country: Germany
facility: Novartis Investigative Site
city: Troisdorf
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Velbert
country: Germany
facility: Novartis Investigative Site
city: Weiden
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: L'Aquila
country: Italy
facility: Novartis Investigative Site
state: AQ
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Lecce
country: Italy
facility: Novartis Investigative Site
state: LE
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Pontedera
country: Italy
facility: Novartis Investigative Site
state: PI
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Amman
country: Jordan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Ashrafieh
country: Lebanon
facility: Novartis Investigative Site
city: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Johor Bahru
country: Malaysia
facility: Novartis Investigative Site
state: Johor
city: Kuching
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Oaxaca
country: Mexico
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Breda
country: Netherlands
facility: Novartis Investigative Site
city: Den Haag
country: Netherlands
facility: Novartis Investigative Site
city: Deventer
country: Netherlands
facility: Novartis Investigative Site
city: Enschede
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Hoofddorp
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Nieuwegein
country: Netherlands
facility: Novartis Investigative Site
city: Roermond
country: Netherlands
facility: Novartis Investigative Site
city: Sittard-Geleen
country: Netherlands
facility: Novartis Investigative Site
city: Tilburg
country: Netherlands
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Konin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Arkhangelsk
country: Russian Federation
facility: Novartis Investigative Site
city: Tambov
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Granada
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Madrid
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sant Joan Despi
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: A Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Alcorcon
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: San Sebastian de los Reyes
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Eskilstuna
country: Sweden
facility: Novartis Investigative Site
city: Sundsvall
country: Sweden
facility: Novartis Investigative Site
city: Vaxjo
country: Sweden
facility: Novartis Investigative Site
city: Aarau
country: Switzerland
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
state: Devon
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Burris HA, Chan A, Bardia A, Thaddeus Beck J, Sohn J, Neven P, Tripathy D, Im SA, Chia S, Esteva FJ, Hart L, Zarate JP, Ridolfi A, Lorenc KR, Yardley DA. Safety and impact of dose reductions on efficacy in the randomised MONALEESA-2, -3 and -7 trials in hormone receptor-positive, HER2-negative advanced breast cancer. Br J Cancer. 2021 Aug;125(5):679-686. doi: 10.1038/s41416-021-01415-9. Epub 2021 Jun 22.
citation: Slamon DJ, Neven P, Chia S, Jerusalem G, De Laurentiis M, Im S, Petrakova K, Valeria Bianchi G, Martin M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Ji Y, Wang C, Deore U, Chakravartty A, Zarate JP, Taran T, Fasching PA. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021 Aug;32(8):1015-1024. doi: 10.1016/j.annonc.2021.05.353. Epub 2021 Jun 5.
citation: Prat A, Chaudhury A, Solovieff N, Pare L, Martinez D, Chic N, Martinez-Saez O, Braso-Maristany F, Lteif A, Taran T, Babbar N, Su F. Correlative Biomarker Analysis of Intrinsic Subtypes and Efficacy Across the MONALEESA Phase III Studies. J Clin Oncol. 2021 May 1;39(13):1458-1467. doi: 10.1200/JCO.20.02977. Epub 2021 Mar 26.
citation: Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martin M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Sondhi M, Wang Y, Chakravartty A, Rodriguez-Lorenc K, Taran T, Jerusalem G. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2020 Feb 6;382(6):514-524. doi: 10.1056/NEJMoa1911149. Epub 2019 Dec 11.
citation: Yardley DA. MONALEESA clinical program: a review of ribociclib use in different clinical settings. Future Oncol. 2019 Aug;15(23):2673-2686. doi: 10.2217/fon-2019-0130. Epub 2019 Jul 15.
citation: Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martin M, Nusch A, Sonke GS, De la Cruz-Merino L, Beck JT, Pivot X, Vidam G, Wang Y, Rodriguez Lorenc K, Miller M, Taran T, Jerusalem G. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol. 2018 Aug 20;36(24):2465-2472. doi: 10.1200/JCO.2018.78.9909. Epub 2018 Jun 3.