Clinical trial NCT02437318: Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant in Men and Postmenopausal Women With Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment.
Official title: A Phase III Randomized Double-blind, Placebo Controlled Study of Alpelisib in Combination With Fulvestrant for Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative Advanced Breast Cancer Which Progressed on or After Aromatase Inhibitor Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: BYL719
HR+
HER2-negative
advanced breast cancer
alpelisib
fulvestrant
PI3K
Phase III
ER+
PgR+
men
postmenopausal
aromatase inhibitor
neoplasms
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-05-07
Enrollment: 572
Sex: ALL
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: To determine whether treatment with alpelisib plus fulvestrant prolonged progression-free survival (PFS) compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 (HER2)-negative advanced breast cancer, who received prior treatment with an aromatase Inhibitor (AI) either as (neo)adjuvant or for advanced disease.

Detailed description: This was a randomized, double-blind, placebo-controlled, international multicenter Phase III study that evaluated the efficacy and safety of treatment with alpelisib plus fulvestrant versus placebo plus fulvestrant in men and postmenopausal women with HR-positive, HER2-negative advanced breast cancer which had progressed on or after AI treatment.

Subjects were allocated to either the PIK3CA mutant or PIK3CA non-mutant cohort, based on central testing of hotspot-mutations in tumor tissue. Subjects with unknown results were not eligible. Within each cohort, subjects were randomized in a 1:1 ratio to receive either alpelisib 300 mg orally once daily (q.d.), in combination with fulvestrant 500 mg intramuscular (i.m.) on Days 1 and 15 of Cycle 1 and Day 1 of a 28-day cycle thereafter, or placebo daily in combination with fulvestrant 500 mg following the same treatment regimen.

Subjects were treated until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason. All subjects who discontinued study treatment were followed for safety, until 30 days after last study treatment administration, except in the case of death, loss to follow-up, or withdrawal of consent.

Subjects who discontinued study treatment for reasons other than disease progression or withdrawal of consent, were followed until disease progression, death, withdrawal of consent, loss to follow-up, or subject/guardian decision (post-treatment efficacy follow-up).

Finally, all subjects were followed for survival after discontinuation of study treatment and tumor evaluations until the subject's death, loss to follow-up, or withdrawal of consent for survival follow-up (post-treatment survival follow-up)

Eligibility criteria: Inclusion Criteria:

* If female, the patient was postmenopausal.
* The patient had identified PIK3CA status.
* Patients could be:
* Relapsed with documented evidence of progression while on (neo)adjuvant endocrine therapy or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease.
* Relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression while on or after only one line of endocrine therapy for metastatic disease.
* Newly diagnosed with advanced breast cancer, then relapsed with documented evidence of progression while on or after only one line of endocrine therapy.
* The patient had recurrence or progression of the disease during or after AI therapy (i.e., letrozole, anastrozole, exemestane).
* The patient had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive breast cancer by a local laboratory and had HER2 negative breast cancer.
* The patient had either measurable disease per RECIST 1.1 criteria or at least one predominantly lytic bone lesion present.
* The patient had adequate bone marrow function.

Exclusion Criteria:

* The patient had symptomatic visceral disease or any disease burden that made the patient ineligible for endocrine therapy per the investigator's best judgment.
* The patient had received prior treatment with chemotherapy (except for neoadjuvant/adjuvant chemotherapy), fulvestrant, any PI3K, mTOR, or AKT inhibitor (pre-treatment with CDK4/6 inhibitors was allowed).
* The patient had inflammatory breast cancer at screening.
* Patients had Child pugh score B or C.
* Patients had an established diagnosis of diabetes mellitus type I or uncontrolled type II.
* The patient had Eastern Cooperative Oncology Group (ECOG) performance status 2 or more.
* The patient had CNS involvement unless he/she was at least 4 weeks from prior therapy completion to starting the study treatment and had a stable CNS tumor at the time of screening and was not receiving steroids and/or enzyme-inducing antiepileptic medications for brain metastases.
* The patient had participated in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever was longer.
* The patient had a history of acute pancreatitis within 1 year of screening or a past medical history of chronic pancreatitis.
* The patient relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for metastatic disease.

Primary outcomes:
measure: Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort
timeFrame: Once approximately 243 PFS events in the PIK3CA mutant cohort had been observed, up to 33.3 months
Secondary outcomes:
measure: Overall Survival (OS) in the PIK3CA Mutant Cohort
timeFrame: Once approximately 178 deaths in the PIK3CA mutant cohort had been observed, up to 55.7 months
measure: PFS Per Investigator Assessment in the PIK3CA Non-mutant Cohort
timeFrame: Up to 56.4 months
measure: OS in the PIK3CA Non-mutant Cohort
timeFrame: Up to 56.4 months
measure: Overall Response Rate (ORR) Per Investigator Assessment
timeFrame: Up to 56.4 months
measure: Clinical Benefit Rate (CBR) Per Investigator Assessment
timeFrame: Up to 56.4 months
measure: Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score From Baseline
timeFrame: From baseline up to 56.4 months
measure: Time to 10% Deterioration in the Global Health Status (GHS) /Quality of Life (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 55.7 months
measure: Change From Baseline in the GHS/QOL Scale Score of the EORTC QLQ-C30
timeFrame: Baseline, every 8 weeks after randomization during the first 18 months and thereafter every 12 weeks, up to 120 weeks.
measure: Trough Plasma Concentration of Alpelisib
timeFrame: Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2, 4, 6 and 8. Cycle = 28 days
measure: Trough Plasma Concentration of Fulvestrant
timeFrame: Day 15 of Cycle 1, then Day 1 of Cycles 2, 4, 6 and 8. Cycle = 28 days
measure: PFS Per Investigator Criteria in Subjects With PIK3CA Mutation Status Measured in ctDNA at Baseline
timeFrame: From baseline up to 56.4 months
Other outcomes:
measure: Updated PFS Per Investigator Assessment in the PIK3CA Mutant Cohort (Longer Follow-up)
timeFrame: Up to 55.7 months
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: Scripps Green Hospital
state: California
city: San Diego
country: United States
facility: Kaiser Permanent Southern Californi
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists-North
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Naperville
country: United States
facility: Edward Cancer Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology Hematology Inc
state: Indiana
city: Topeka
country: United States
facility: St Francis Health Comprehensive Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Owosso
country: United States
facility: Detroit Clinical Research Center
state: Michigan
city: Kansas City
country: United States
facility: St Lukes Cancer Institute
state: Missouri
city: Billings
country: United States
facility: St Vincent Frontier Cancer Center
state: Montana
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Cleveland
country: United States
facility: University Hospitals of Cleveland Seidman Cancer Center
state: Ohio
city: Corvallis
country: United States
facility: Good Samaritan Regional Medical Center
state: Oregon
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health Upstate
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer
state: South Dakota
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology PA Dallas Presbyterian Hospital
state: Texas
city: El Paso
country: United States
facility: El Paso Texas Oncology
state: Texas
city: San Antonio
country: United States
facility: Mays Cancer Ctr Uthsa Mdacc
state: Texas
city: Tyler
country: United States
facility: Texas Oncology Northeast Texas
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Berazategui
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rio Negro
country: Argentina
facility: Novartis Investigative Site
state: Viedma
city: La Rioja
country: Argentina
facility: Novartis Investigative Site
city: Wahroonga
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Wooloongabba
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Elizabeth Vale
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Linz
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: Brussel
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
city: Libramont
country: Belgium
facility: Novartis Investigative Site
city: Ottignies
country: Belgium
facility: Novartis Investigative Site
city: Verviers
country: Belgium
facility: Novartis Investigative Site
city: Natal
country: Brazil
facility: Novartis Investigative Site
state: RN
city: Lajeado
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Jose do Rio Preto
country: Brazil
facility: Novartis Investigative Site
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Cambridge
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: Quebec
country: Canada
facility: Novartis Investigative Site
city: Temuco
country: Chile
facility: Novartis Investigative Site
state: Araucania
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Vina del Mar
country: Chile
facility: Novartis Investigative Site
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Zlin
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Hradec Kralove
country: Czechia
facility: Novartis Investigative Site
state: CZE
city: Prague 8
country: Czechia
facility: Novartis Investigative Site
city: Marseille cedex 20
country: France
facility: Novartis Investigative Site
state: Bouches Du Rhone
city: Angers 02
country: France
facility: Novartis Investigative Site
city: Avignon
country: France
facility: Novartis Investigative Site
city: Caen
country: France
facility: Novartis Investigative Site
city: Clermont-Ferrand
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: La Roche sur Yon cedex 9
country: France
facility: Novartis Investigative Site
city: Le Chesnay
country: France
facility: Novartis Investigative Site
city: Levallois Perret
country: France
facility: Novartis Investigative Site
city: Lyon 08
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Nimes
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Saint Herblain
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Luebeck
country: Germany
facility: Novartis Investigative Site
state: Schleswig-Holstein
city: Aschaffenburg
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Friedrichshafen
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Homburg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Potsdam
country: Germany
facility: Novartis Investigative Site
city: Recklinghausen
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Velbert
country: Germany
facility: Novartis Investigative Site
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Pokfulam
country: Hong Kong
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
state: Pest Megye
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Nyiregyhaza
country: Hungary
facility: Novartis Investigative Site
city: Szekszard
country: Hungary
facility: Novartis Investigative Site
city: Vijayawada
country: India
facility: Novartis Investigative Site
state: Andhra Pradesh
city: Nagpur
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Mumbai
country: India
facility: Novartis Investigative Site
city: Beer Sheva
country: Israel
facility: Novartis Investigative Site
city: Haifa
country: Israel
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: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Chieti
country: Italy
facility: Novartis Investigative Site
state: CH
city: Meldola
country: Italy
facility: Novartis Investigative Site
state: FC
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Palermo
country: Italy
facility: Novartis Investigative Site
state: PA
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Pontedera
country: Italy
facility: Novartis Investigative Site
state: PI
city: Aviano
country: Italy
facility: Novartis Investigative Site
state: PN
city: Rionero in Vulture
country: Italy
facility: Novartis Investigative Site
state: PZ
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Savona
country: Italy
facility: Novartis Investigative Site
state: SV
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Negrar
country: Italy
facility: Novartis Investigative Site
state: VR
city: Sassari
country: Italy
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Matsuyama
country: Japan
facility: Novartis Investigative Site
state: Ehime
city: Maebashi city
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Akashi
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Isehara
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Kitaadachi-gun
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Minato Ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Kagoshima
country: Japan
facility: Novartis Investigative Site
city: Kumamoto
country: Japan
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: 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: Saida
country: Lebanon
facility: Novartis Investigative Site
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: NL
city: San Luis Potosi
country: Mexico
facility: Novartis Investigative Site
city: Venray
country: Netherlands
facility: Novartis Investigative Site
state: CE
city: Terneuzen
country: Netherlands
facility: Novartis Investigative Site
city: San Borja
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Surquillo
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Floresti
country: Romania
facility: Novartis Investigative Site
state: Cluj
city: Craiova
country: Romania
facility: Novartis Investigative Site
state: Dolj
city: Iasi
country: Romania
facility: Novartis Investigative Site
city: Arkhangelsk
country: Russian Federation
facility: Novartis Investigative Site
city: Ryazan
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Jerez
country: Spain
facility: Novartis Investigative Site
state: Cadiz
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluna
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Alicante
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Castellon
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Badajoz
country: Spain
facility: Novartis Investigative Site
state: Extremadura
city: Caceres
country: Spain
facility: Novartis Investigative Site
state: Extremadura
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Palma De Mallorca
country: Spain
facility: Novartis Investigative Site
state: Islas Baleares
city: Pozuelo de Alarcon
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: El Palmar
country: Spain
facility: Novartis Investigative Site
state: Murcia
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: Madrid
country: Spain
facility: Novartis Investigative Site
city: Gavle
country: Sweden
facility: Novartis Investigative Site
city: Oerebro
country: Sweden
facility: Novartis Investigative Site
city: Vasteras
country: Sweden
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Ciruelos EM, Rugo HS, Mayer IA, Levy C, Forget F, Delgado Mingorance JI, Safra T, Masuda N, Park YH, Juric D, Conte P, Campone M, Loibl S, Iwata H, Zhou X, Park J, Ridolfi A, Lorenzo I, Andre F. Patient-Reported Outcomes in Patients With PIK3CA-Mutated Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer From SOLAR-1. J Clin Oncol. 2021 Jun 20;39(18):2005-2015. doi: 10.1200/JCO.20.01139. Epub 2021 Mar 29.
citation: Andre F, Ciruelos EM, Juric D, Loibl S, Campone M, Mayer IA, Rubovszky G, Yamashita T, Kaufman B, Lu YS, Inoue K, Papai Z, Takahashi M, Ghaznawi F, Mills D, Kaper M, Miller M, Conte PF, Iwata H, Rugo HS. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021 Feb;32(2):208-217. doi: 10.1016/j.annonc.2020.11.011. Epub 2020 Nov 25.
citation: Rugo HS, Andre F, Yamashita T, Cerda H, Toledano I, Stemmer SM, Jurado JC, Juric D, Mayer I, Ciruelos EM, Iwata H, Conte P, Campone M, Wilke C, Mills D, Lteif A, Miller M, Gaudenzi F, Loibl S. Time course and management of key adverse events during the randomized phase III SOLAR-1 study of PI3K inhibitor alpelisib plus fulvestrant in patients with HR-positive advanced breast cancer. Ann Oncol. 2020 Aug;31(8):1001-1010. doi: 10.1016/j.annonc.2020.05.001. Epub 2020 May 13.
citation: Andre F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Papai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D; SOLAR-1 Study Group. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20):1929-1940. doi: 10.1056/NEJMoa1813904.