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. (SOLAR-1)

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: Alpelisib; Drug: Placebo

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)

• Study Type: Interventional
• Enrollment (Actual): 572
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • La Rioja, Argentina, 5300
    • Novartis Investigative Site
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, B1884BBF
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1125ABD
      • Novartis Investigative Site
  • Viedma
    • Rio Negro, Viedma, Argentina, 8500
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Wahroonga, New South Wales, Australia, 2076
      • Novartis Investigative Site
  • Queensland
    • Wooloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Novartis Investigative Site
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Novartis Investigative Site
• Austria
  • Linz, Austria, 4010
    • Novartis Investigative Site
  • Wien, Austria, 1090
    • Novartis Investigative Site
• Belgium
  • Brussel, Belgium, 1090
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
  • Edegem, Belgium, 2650
    • Novartis Investigative Site
  • Libramont, Belgium, 6800
    • Novartis Investigative Site
  • Ottignies, Belgium, 1340
    • Novartis Investigative Site
  • Verviers, Belgium, 4800
    • Novartis Investigative Site
  • Oost Vlaanderen
    • Sint Niklaas, Oost Vlaanderen, Belgium, 9100
      • Novartis Investigative Site
• Brazil
  • Sao Jose do Rio Preto, Brazil, 15090 000
    • Novartis Investigative Site
  • Sao Paulo, Brazil, 01236 030
    • Novartis Investigative Site
  • RN
    • Natal, RN, Brazil, 59075 740
      • Novartis Investigative Site
  • RS
    • Lajeado, RS, Brazil, 95900-000
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 04014-002
      • Novartis Investigative Site
• Bulgaria
  • Plovdiv, Bulgaria, 4004
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1756
    • Novartis Investigative Site
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
  • Varna, Bulgaria, 9002
    • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1S 4L8
    • Novartis Investigative Site
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Novartis Investigative Site
  • Ontario
    • Cambridge, Ontario, Canada, N1R 3G2
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5B 1W8
      • Novartis Investigative Site
• Chile
  • Santiago, Chile, 8420383
    • Novartis Investigative Site
  • Vina del Mar, Chile, 2520612
    • Novartis Investigative Site
  • Araucania
    • Temuco, Araucania, Chile, 4810469
      • Novartis Investigative Site
• Czechia
  • Prague 8, Czechia, 180 00
    • Novartis Investigative Site
  • CZE
    • Hradec Kralove, CZE, Czechia, 500 05
      • Novartis Investigative Site
  • Czech Republic
    • Praha 4, Czech Republic, Czechia, 140 46
      • Novartis Investigative Site
    • Zlin, Czech Republic, Czechia, 762 75
      • Novartis Investigative Site
• France
  • Angers 02, France, 49055
    • Novartis Investigative Site
  • Avignon, France, 84082
    • Novartis Investigative Site
  • Caen, France, 14021
    • Novartis Investigative Site
  • Clermont-Ferrand, France, 63011
    • Novartis Investigative Site
  • Creteil, France, 94010
    • Novartis Investigative Site
  • La Roche sur Yon cedex 9, France, 85925
    • Novartis Investigative Site
  • Le Chesnay, France, 78150
    • Novartis Investigative Site
  • Levallois Perret, France, 92309
    • Novartis Investigative Site
  • Lyon 08, France, 69373
    • Novartis Investigative Site
  • Montpellier, France, 34070
    • Novartis Investigative Site
  • Nimes, France, 30029
    • Novartis Investigative Site
  • Rouen, France, 76038
    • Novartis Investigative Site
  • Saint Herblain, France, 44805
    • Novartis Investigative Site
  • Toulouse, France, 31059
    • Novartis Investigative Site
  • Villejuif, France, 94800
    • Novartis Investigative Site
  • Bouches Du Rhone
    • Marseille cedex 20, Bouches Du Rhone, France, 13915
      • Novartis Investigative Site
• Germany
  • Aschaffenburg, Germany, 63739
    • Novartis Investigative Site
  • Frankfurt, Germany, 60389
    • Novartis Investigative Site
  • Friedrichshafen, Germany, 88045
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Leipzig, Germany, 04277
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
  • Potsdam, Germany, 14467
    • Novartis Investigative Site
  • Recklinghausen, Germany, 45657
    • Novartis Investigative Site
  • Rostock, Germany, 18059
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Velbert, Germany, 42551
    • Novartis Investigative Site
  • Schleswig-Holstein
    • Luebeck, Schleswig-Holstein, Germany, 23563
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 18547
    • Novartis Investigative Site
  • Athens, Greece, 11528
    • Novartis Investigative Site
  • GR
    • Thessaloniki, GR, Greece, 564 29
      • Novartis Investigative Site
• Hong Kong
  • Pokfulam, Hong Kong
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H 1122
    • Novartis Investigative Site
  • Nyiregyhaza, Hungary, 4400
    • Novartis Investigative Site
  • Szekszard, Hungary, 7100
    • Novartis Investigative Site
  • Pest Megye
    • Budapest, Pest Megye, Hungary, 1134
      • Novartis Investigative Site
• India
  • Mumbai, India, 400 012
    • Novartis Investigative Site
  • Andhra Pradesh
    • Vijayawada, Andhra Pradesh, India, 520002
      • Novartis Investigative Site
  • Maharashtra
    • Nagpur, Maharashtra, India, 440010
      • Novartis Investigative Site
• Israel
  • Beer Sheva, Israel, 8457108
    • Novartis Investigative Site
  • Haifa, Israel, 3109601
    • Novartis Investigative Site
  • Petach Tikva, Israel, 4941492
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • Sassari, Italy, 07100
    • Novartis Investigative Site
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • CH
    • Chieti, CH, Italy, 66100
      • Novartis Investigative Site
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35100
      • Novartis Investigative Site
  • PI
    • Pontedera, PI, Italy, 56025
      • Novartis Investigative Site
  • PN
    • Aviano, PN, Italy, 33081
      • Novartis Investigative Site
  • PZ
    • Rionero in Vulture, PZ, Italy, 85028
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
  • SV
    • Savona, SV, Italy, 17100
      • Novartis Investigative Site
  • TO
    • Torino, TO, Italy, 10126
      • Novartis Investigative Site
  • VR
    • Negrar, VR, Italy, 37024
      • Novartis Investigative Site
• Japan
  • Kagoshima, Japan, 892-0833
    • Novartis Investigative Site
  • Kumamoto, Japan, 860-8556
    • Novartis Investigative Site
  • Aichi
    • Nagoya, Aichi, Japan, 464 8681
      • Novartis Investigative Site
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • Novartis Investigative Site
  • Gunma
    • Maebashi city, Gunma, Japan, 371 8511
      • Novartis Investigative Site
  • Hokkaido
    • Sapporo-city, Hokkaido, Japan, 003-0804
      • Novartis Investigative Site
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Novartis Investigative Site
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 241-8515
      • Novartis Investigative Site
  • Osaka
    • Osaka-city, Osaka, Japan, 540-0006
      • Novartis Investigative Site
    • Osaka-city, Osaka, Japan, 541-8567
      • Novartis Investigative Site
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Novartis Investigative Site
  • Tokyo
    • Chuo ku, Tokyo, Japan, 104 8560
      • Novartis Investigative Site
    • Minato Ku, Tokyo, Japan, 105-8470
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 05505
    • Novartis Investigative Site
  • Gyeonggi Do
    • Bundang Gu, Gyeonggi Do, Korea, Republic of, 13620
      • Novartis Investigative Site
  • Korea
    • Gyeonggi do, Korea, Korea, Republic of, 10408
      • Novartis Investigative Site
• Lebanon
  • Ashrafieh, Lebanon, 166830
    • Novartis Investigative Site
  • Beirut, Lebanon, 10999
    • Novartis Investigative Site
  • Saida, Lebanon, 652
    • Novartis Investigative Site
• Mexico
  • San Luis Potosi, Mexico, 78200
    • Novartis Investigative Site
  • NL
    • Monterrey, NL, Mexico, 64320
      • Novartis Investigative Site
• Netherlands
  • Terneuzen, Netherlands, 4535 PA
    • Novartis Investigative Site
  • CE
    • Venray, CE, Netherlands, 5801
      • Novartis Investigative Site
• Peru
  • Lima, Peru, LIMA 27
    • Novartis Investigative Site
  • Lima
    • San Borja, Lima, Peru, 41
      • Novartis Investigative Site
    • Surquillo, Lima, Peru, 34
      • Novartis Investigative Site
• Romania
  • Iasi, Romania, 700483
    • Novartis Investigative Site
  • Cluj
    • Floresti, Cluj, Romania, 407280
      • Novartis Investigative Site
  • Dolj
    • Craiova, Dolj, Romania, 200347
      • Novartis Investigative Site
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Novartis Investigative Site
  • Ryazan, Russian Federation, 390011
    • Novartis Investigative Site
  • St Petersburg, Russian Federation, 197758
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28050
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
  • Cadiz
    • Jerez, Cadiz, Spain, 11407
      • Novartis Investigative Site
  • Cataluna
    • Barcelona, Cataluna, Spain, 08024
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03010
      • Novartis Investigative Site
    • Castellon, Comunidad Valenciana, Spain, 12002
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
  • Extremadura
    • Badajoz, Extremadura, Spain, 06080
      • Novartis Investigative Site
    • Caceres, Extremadura, Spain, 10003
      • Novartis Investigative Site
  • Galicia
    • Santiago De Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
  • Islas Baleares
    • Palma De Mallorca, Islas Baleares, Spain, 07120
      • Novartis Investigative Site
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Novartis Investigative Site
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Novartis Investigative Site
• Sweden
  • Gavle, Sweden, SE-801 87
    • Novartis Investigative Site
  • Oerebro, Sweden, 70185
    • Novartis Investigative Site
  • Vasteras, Sweden, 721 89
    • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Novartis Investigative Site
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • Plymouth, United Kingdom, PL6 8DH
    • Novartis Investigative Site
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Arizona
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • Duarte, California, United States, 91010 3000
      • City of Hope National Medical Center
    • La Jolla, California, United States, 92037
      • Scripps Green Hospital
    • San Diego, California, United States, 92120
      • Kaiser Permanent Southern Californi
    • San Francisco, California, United States, 94115
      • UCSF
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists-North
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Evanston, Illinois, United States, 60201
      • NorthShore University Health System
    • Naperville, Illinois, United States, 60540
      • Edward Cancer Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Medical Oncology Hematology Inc
  • Kansas
    • Topeka, Kansas, United States, 66606-169
      • St Francis Health Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Michigan
    • Owosso, Michigan, United States, 48867
      • Detroit Clinical Research Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St Lukes Cancer Institute
  • Montana
    • Billings, Montana, United States, 59102
      • St Vincent Frontier Cancer Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland Seidman Cancer Center
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • Good Samaritan Regional Medical Center
  • Pennsylvania
    • Lancaster, Pennsylvania, United States, 17604
      • Lancaster General Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Upstate
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • SCRI Oncology Partners
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Oncology PA Dallas Presbyterian Hospital
    • El Paso, Texas, United States, 79902
      • El Paso Texas Oncology
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Ctr Uthsa Mdacc
    • Tyler, Texas, United States, 75702
      • Texas Oncology Northeast Texas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fulvestrant + alpelisib; Subjects treated with alpelisib (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)	Drug: Fulvestrant; 500 mg of fulvestrant administered via intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle; Drug: Alpelisib; 300 mg of alpelisib tablets for oral use administered once daily; Other Names: BYL719
Placebo Comparator: Fulvestrant + placebo; Subjects were treated with placebo (300 mg; oral; once daily) in combination with fulvestrant (500 mg; intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle)	Drug: Fulvestrant; 500 mg of fulvestrant administered via intramuscular injection on Day 1 and Day 15 of Cycle 1, and then Day 1 of each subsequent 28-day cycle; Drug: Placebo; 300 mg of placebo tablets for oral use administered once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) Per Investigator Assessment in the PIK3CA Mutant Cohort	PFS was defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. If a patient did not have an event, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Progression was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Once approximately 243 PFS events in the PIK3CA mutant cohort had been observed, up to 33.3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in the PIK3CA Mutant Cohort	OS was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive. The OS distribution was estimated using Kaplan-Meier methodology.	Once approximately 178 deaths in the PIK3CA mutant cohort had been observed, up to 55.7 months
PFS Per Investigator Assessment in the PIK3CA Non-mutant Cohort	PFS was defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. If a patient did not have an event, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Progression was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Up to 56.4 months
OS in the PIK3CA Non-mutant Cohort	OS was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive. The OS distribution was estimated using Kaplan-Meier methodology.	Up to 56.4 months
Overall Response Rate (ORR) Per Investigator Assessment	ORR was defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.	Up to 56.4 months
Clinical Benefit Rate (CBR) Per Investigator Assessment	Clinical benefit rate was defined as the percentage of patients with a best overall response of CR or PR or stable disease (SD) or Non-CR/Non-PD lasting more than 24 weeks based on local investigator assessment according to RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to < 10 mm. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.	Up to 56.4 months
Time to Definitive Deterioration of Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score From Baseline	ECOG PS categorized patients based on their ability to perform daily activities and self-care, with scores ranging from 0 to 5. A score of 0 indicated no restrictions in activity, while higher scores indicated increasing limitations. Time to definitive deterioration of ECOG PS by one score was defined as the time from the date of randomization to the date of the event, defined as experiencing at least one score lower than the baseline. A deterioration was considered definitive if no improvements in the ECOG PS were observed at a subsequent time. The Kaplan-Meier method was used to estimate the distribution. Patients receiving any further therapy prior to definitive worsening were censored at their date of last assessment prior to start of therapy. Patients that had not worsened at the data cutoff point were censored at the date of last assessment.	From baseline up to 56.4 months
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)	The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.The time to definitive 10% deterioration was defined as the time from the date of randomization to the date of event, which was defined as at least 10% relative to baseline worsening of the GHS/QoL score (without further improvement above the threshold) or death due to any cause. The Kaplan-Meier method was used to estimate the distribution. If a patient had not had an event, time to deterioration was censored at the date of the last adequate QoL evaluation.	From baseline up to 55.7 months
Change From Baseline in the GHS/QOL Scale Score of the EORTC QLQ-C30	The EORTC QLQ-C30 is a questionnaire that includes 5 functional scales, 3 symptom scales, 1 GHS/QoL scale, and 6 single items. GHS/QoL scale score ranges between 0 and 100. A high score for GHS/QoL represents better functioning or QoL.The change from baseline in the GHS/QoL score was assessed. A positive change from baseline indicated improvement. For each cohort, this analysis only included assessments up to the time point where there were at least 10 patients on each of the 2 treatment groups.	Baseline, every 8 weeks after randomization during the first 18 months and thereafter every 12 weeks, up to 120 weeks.
Trough Plasma Concentration of Alpelisib	Pre-dose plasma concentrations of alpelisib were assessed. Only participants randomized to the alpelisib + fulvestrant arm were included in this analysis.	Day 8 and Day 15 of Cycle 1, then Day 1 of Cycles 2, 4, 6 and 8. Cycle = 28 days
Trough Plasma Concentration of Fulvestrant	Pre-dose plasma concentrations of fulvestrant were assessed.	Day 15 of Cycle 1, then Day 1 of Cycles 2, 4, 6 and 8. Cycle = 28 days
PFS Per Investigator Criteria in Subjects With PIK3CA Mutation Status Measured in ctDNA at Baseline	PFS was defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. If a patient did not have an event, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Subjects were analyzed according to the PIK3CA mutation status (mutant or non-mutant) as identified using plasma ctDNA. Progression was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	From baseline up to 56.4 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Updated PFS Per Investigator Assessment in the PIK3CA Mutant Cohort (Longer Follow-up)	PFS was defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS was assessed via a local radiology assessment according to RECIST 1.1. If a patient did not have an event, PFS was censored at the date of last adequate tumor assessment. The PFS distribution was estimated using Kaplan-Meier methodology. This analysis was conducted at the time of the final OS analysis (when approximately 178 deaths in the PIK3CA mutant cohort had been achieved) and includes a longer follow-up time. Progression was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Up to 55.7 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2015
• Primary Completion (Actual): June 12, 2018
• Study Completion (Actual): June 9, 2023

Study Registration Dates

• First Submitted: April 22, 2015
• First Submitted That Met QC Criteria: May 4, 2015
• First Posted (Estimated): May 7, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Phase III; BYL719; neoplasms; HR+; postmenopausal; men; advanced breast cancer; aromatase inhibitor; ER+; PI3K; HER2-negative; fulvestrant; alpelisib; PgR+
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Receptor Antagonists; Estrogen Antagonists; Fulvestrant
• Other Study ID Numbers: CBYL719C2301; 2015-000340-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No