Clinical trial NCT01958021: Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer
Official title: A Randomized Double-blind, Placebo-controlled Study of LEE011 in Combination With Letrozole for the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative, Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Advanced, Metastatic Breast Cancer
Keywords: HR-positive
HER2-negative
Advanced breast cancer
LEE011
Letrozole
CDK
CDK4
CDK6
CDK4/6
Phase III
ER-positive
PR-positive
Postmenopausal
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-10-08
Enrollment: 668
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study was to assess the efficacy of ribociclib, as measured by progression free survival (PFS), in postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who received no prior treatment for advanced disease.

Detailed description: This was an international, multi-center, randomized, double-blinded, placebo controlled Phase III trial to determine the efficacy and safety of treatment with ribociclib plus letrozole versus placebo plus letrozole in postmenopausal women with HR+, HER2-negative advanced breast cancer who received no prior therapy for advanced disease.

Eligible patients were randomized in 1:1 ratio to either ribociclib group or placebo group. Study treatment continued until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

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 (post-treatment efficacy follow-up).

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

Following the final OS analysis (performed when approximately 400 deaths were recorded) and with protocol amendment 10 (dated 30-Apr-2021), participants and investigators were unblinded and those participants in the placebo arm had the opportunity to cross-over to the ribociclib arm to receive ribociclib plus letrozole. Cross-over was optional and was conducted at the investigator's discretion and upon participant consent.

Eligibility criteria: Key Inclusion Criteria:

1. Women with advanced (locoregionally recurrent or metastatic) breast cancer that was not amenable to curative therapy.
2. The patient was postmenopausal. Postmenopausal status was defined either by:

   * Prior bilateral oophorectomy
   * Age ≥60
   * Age \<60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range.
3. There was no prior systemic anti-cancer therapy for advanced disease.
4. The patient had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by the local laboratory.
5. The patient had HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC was 2+, a negative in situ hybridization (FISH, CISH, or SISH) test was required by local laboratory testing.
6. The patient must have had either:

   Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (Tumor lesions previously irradiated or subjected to other locoregional therapy were considered measurable if disease progression at the treated site after completion of therapy was clearly documented). OR If no measurable disease was present, then at least one predominantly lytic bone lesion must have been present (Patients with no measurable disease and only one predominantly lytic bone lesion previously irradiated were eligible if there was documented evidence of disease progression of the bone lesion after irradiation).
7. The patient had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Key Exclusion Criteria:

1. The patient had received any CDK4/6 inhibitor.
2. The patient had received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer.

   Note:
   * Patients who had received (neo) adjuvant therapy for breast cancer were eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole, the disease-free interval had to be greater than 12 months from the completion of treatment until randomization.
   * Patients who had received ≤ 14 days of letrozole or anastrozole for advanced disease prior to randomization were eligible.
   * Any prior (neo) adjuvant anti-cancer therapy had to be stopped at least 5 half-lives or 7 days, whichever was longer, before randomization.
3. The patient was concurrently using other anti-cancer therapy.
4. The patient had a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer.
5. The patient had active cardiac disease or a history of cardiac dysfunction, including any of the following:

   * History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry.
   * History of documented congestive heart failure (New York Heart Association functional classification III-IV).
   * Documented cardiomyopathy.
   * The patient had a Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO).
   * History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months.
   * On screening, any of the following cardiac parameters: bradycardia (heart rate \< 50 at rest), tachycardia (heart rate \> 90 at rest), PR interval \> 220 msec, QRS interval \>109 msec, or QTcF \>450 msec.
   * Systolic blood pressure \>160 or \<90 mmHg.
6. The patient was currently receiving any of the following medications and could not be discontinued 7 days prior to the start of treatment:

   * Medications known to be strong inducers or inhibitors of CYP3A4.
   * Medications known to have a risk of prolonging the QT interval or inducing Torsades de Pointes.
   * Medications with a narrow therapeutic window and predominantly metabolized through CYP3A4.
   * Herbal preparations/medications.

Primary outcomes:
measure: Progression Free Survival (PFS) by Investigator Assessment
timeFrame: Up to 23 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 87 months
measure: Overall Response Rate (ORR) by Investigator Assessment
timeFrame: Up to 23 months
measure: Clinical Benefit Rate (CBR) by Investigator Assessment
timeFrame: Up to 23 months
measure: Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score
timeFrame: From baseline up to 23 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: From baseline up to 23 months
measure: Change From Baseline in the GHS/QoL Scale Score of the EORTC QLQ-C30
timeFrame: Baseline, every 2 cycles for 18 months, then every 3 cycles until last dose; at EOT (within 15 days from last dose);every 8 or 12 weeks post-treatment until progression (post-treatment efficacy visits), assessed up to 23 months. Cycle=28 days
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers
state: Arizona
city: Sedona
country: United States
facility: Arizona Oncology Associates PC HAL
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Jonesboro
country: United States
facility: NEA Baptist Cancer Center
state: Arkansas
city: Berkeley
country: United States
facility: Alta Bates Cancer Center
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center SC-5
state: California
city: Sacramento
country: United States
facility: Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Univ of Colorado School of Medicine
state: Colorado
city: Longmont
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Boynton Beach
country: United States
facility: University Cancer Institute
state: Florida
city: Davie
country: United States
facility: Florida Cancer Research Institute
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Hollywood
country: United States
facility: Memorial Hospital
state: Florida
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: Orlando
country: United States
facility: Florida Retina Institute
state: Florida
city: Pensacola
country: United States
facility: Sacred Heart Medical Oncology
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists-North
state: Florida
city: Decatur
country: United States
facility: Georgia Cancer Specialists
state: Georgia
city: Thomasville
country: United States
facility: Lewis Hall Singletary Onc Ctr at John D. Archbold Mem Hosp.
state: Georgia
city: Honolulu
country: United States
facility: Moanalua Medical Center Attn Oncology Dept
state: Hawaii
city: Chicago
country: United States
facility: University of Illinois Cancer Center at Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital
state: Illinois
city: Indianapolis
country: United States
facility: IU Simon Cancer Center
state: Indiana
city: Baltimore
country: United States
facility: Sidney Kimmel CCC At JH
state: Maryland
city: Frederick
country: United States
facility: Frederick Memorial Hospital
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: Allina Hlth Cancer Inst Minneapolis
state: Minnesota
city: Jackson
country: United States
facility: Jackson Oncology Associates
state: Mississippi
city: Kansas City
country: United States
facility: St Lukes Hos Marion Bloch Neur Inst
state: Missouri
city: Manchester
country: United States
facility: Mercy Medical Research Institute
state: Missouri
city: Nashua
country: United States
facility: Foundation Medical Partners
state: New Hampshire
city: Camden
country: United States
facility: Cooper Cancer Center
state: New Jersey
city: Edison
country: United States
facility: Hackensack Meridian Health
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Glens Falls
country: United States
facility: C R Wood Cancer Center at Glens Falls Hospital
state: New York
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: New York
country: United States
facility: NYU Langone Med Center CV Research
state: New York
city: New York
country: United States
facility: Mount Sinai School Of Medicine
state: New York
city: Durham
country: United States
facility: Duke Univ Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Inc
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Mercy Clinic Oklahoma Communities Mercy Oncology
state: Oklahoma
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Cancer
state: South Dakota
city: Chattanooga
country: United States
facility: Chattanooga Onc And Hem Assoc PC
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Ctr
state: Tennessee
city: Bedford
country: United States
facility: Texas Oncology P A
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Ctr For Cancer And Blood Disorders
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology P A
state: Texas
city: Houston
country: United States
facility: Texas Oncology Houston Memorial City
state: Texas
city: Houston
country: United States
facility: Uni Of TX MD Anderson Cancer Cntr
state: Texas
city: Houston
country: United States
facility: Millennium Research Clin Develop
state: Texas
city: McAllen
country: United States
facility: Texas Oncology
state: Texas
city: Richardson
country: United States
facility: Richardson Hematology Oncology Associates
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology P A
state: Texas
city: Tyler
country: United States
facility: Texas Oncology Northeast Texas
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Salem
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia Inc
state: Virginia
city: Everett
country: United States
facility: Providence Regional Cancer Partnership
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Madison
country: United States
facility: Dean Health System
state: Wisconsin
city: San Miguel De Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: La Rioja
country: Argentina
facility: Novartis Investigative Site
city: Kurralta Park
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: East Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Sint Niklaas
country: Belgium
facility: Novartis Investigative Site
state: Oost Vlaanderen
city: Hasselt
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Namur
country: Belgium
facility: Novartis Investigative Site
city: Wilrijk
country: Belgium
facility: Novartis Investigative Site
city: Ribeirao Preto
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Burnaby
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Kitchener
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Brno Bohunice
country: Czechia
facility: Novartis Investigative Site
city: Liberec
country: Czechia
facility: Novartis Investigative Site
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Aarhus
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Vejle
country: Denmark
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Turku
country: Finland
facility: Novartis Investigative Site
city: Nice
country: France
facility: Novartis Investigative Site
state: Alpes Maritimes
city: Angers 02
country: France
facility: Novartis Investigative Site
city: Avignon
country: France
facility: Novartis Investigative Site
city: Besancon Cedex
country: France
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Saint Herblain
country: France
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Bielefeld
country: Germany
facility: Novartis Investigative Site
state: North Rhine Westphalia
city: Aschaffenburg
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Bottrop
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Fuerth
country: Germany
facility: Novartis Investigative Site
city: Goslar
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Offenbach
country: Germany
facility: Novartis Investigative Site
city: Ravensburg
country: Germany
facility: Novartis Investigative Site
city: Recklinghausen
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Velbert
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
state: Pest Megye
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Gyor
country: Hungary
facility: Novartis Investigative Site
city: Gyula
country: Hungary
facility: Novartis Investigative Site
city: Cork
country: Ireland
facility: Novartis Investigative Site
city: Dublin 4
country: Ireland
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Lecco
country: Italy
facility: Novartis Investigative Site
state: LC
city: Messina
country: Italy
facility: Novartis Investigative Site
state: ME
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Aviano
country: Italy
facility: Novartis Investigative Site
state: PN
city: Reggio Calabria
country: Italy
facility: Novartis Investigative Site
state: RC
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Candiolo
country: Italy
facility: Novartis Investigative Site
state: TO
city: Terni
country: Italy
facility: Novartis Investigative Site
state: TR
city: Viterbo
country: Italy
facility: Novartis Investigative Site
state: VT
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Bundang Gu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Gyeonggi do
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
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: Beirut
country: Lebanon
facility: Novartis Investigative Site
city: Saida
country: Lebanon
facility: Novartis Investigative Site
city: Sittard-Geleen
country: Netherlands
facility: Novartis Investigative Site
state: BG
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
state: Zuid Holland
city: Alkmaar
country: Netherlands
facility: Novartis Investigative Site
city: Deventer
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Maastricht
country: Netherlands
facility: Novartis Investigative Site
city: Tilburg
country: Netherlands
facility: Novartis Investigative Site
city: Zoetermeer
country: Netherlands
facility: Novartis Investigative Site
city: Zwolle
country: Netherlands
facility: Novartis Investigative Site
city: Bergen
country: Norway
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Arkhangelsk
country: Russian Federation
facility: Novartis Investigative Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Novartis Investigative Site
city: Ryazan
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
state: Gauteng
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluna
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz De Tenerife
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
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: Goteborg
country: Sweden
facility: Novartis Investigative Site
city: Joenkoeping
country: Sweden
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Vaxjo
country: Sweden
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: New Taipei City
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Diyarbakir
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Truro
country: United Kingdom
facility: Novartis Investigative Site
state: Cornwall
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte P, Cameron DA, Andre F, Arteaga CL, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O'Shaughnessy J. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022 Mar 10;386(10):942-950. doi: 10.1056/NEJMoa2114663.
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: 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: 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: Hortobagyi GN. Ribociclib for the first-line treatment of advanced hormone receptor-positive breast cancer: a review of subgroup analyses from the MONALEESA-2 trial. Breast Cancer Res. 2018 Oct 19;20(1):123. doi: 10.1186/s13058-018-1050-7.
citation: Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Mondal S, Su F, Miller M, Elmeliegy M, Germa C, O'Shaughnessy J. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018 Jul 1;29(7):1541-1547. doi: 10.1093/annonc/mdy155.
citation: Janni W, Alba E, Bachelot T, Diab S, Gil-Gil M, Beck TJ, Ryvo L, Lopez R, Tsai M, Esteva FJ, Aunon PZ, Kral Z, Ward P, Richards P, Pluard TJ, Sutradhar S, Miller M, Campone M. First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2- advanced breast cancer: Tumor response and pain reduction in the phase 3 MONALEESA-2 trial. Breast Cancer Res Treat. 2018 Jun;169(3):469-479. doi: 10.1007/s10549-017-4658-x. Epub 2018 Feb 5.
citation: Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, Andre F, Winer EP, Janni W, Verma S, Conte P, Arteaga CL, Cameron DA, Petrakova K, Hart LL, Villanueva C, Chan A, Jakobsen E, Nusch A, Burdaeva O, Grischke EM, Alba E, Wist E, Marschner N, Favret AM, Yardley D, Bachelot T, Tseng LM, Blau S, Xuan F, Souami F, Miller M, Germa C, Hirawat S, O'Shaughnessy J. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med. 2016 Nov 3;375(18):1738-1748. doi: 10.1056/NEJMoa1609709. Epub 2016 Oct 7.