VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor–Positive/HER2−/PIK3CA Wild-Type Advanced Breast Cancer
Abstract
PURPOSE Gedatolisib potently targets all four class I PI3K isoforms and mTORC1 and mTORC2 to comprehensively block the PI3K/AKT/mTOR pathway and has shown compelling activity in early clinical trials with palbociclib and fulvestrant. METHODS This phase III randomized trial (VIKTORIA-1; ClinicalTrials.gov identifier: NCT05501886 ) evaluated the efficacy of gedatolisib-based therapy, comparing gedatolisib, palbociclib, and fulvestrant (gedatolisib triplet) and gedatolisib plus fulvestrant (gedatolisib doublet) with fulvestrant monotherapy in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HER2−), PIK3CA wild-type (WT) advanced breast cancer. Eligible patients had disease progression during or after CDK4/6 inhibitor and aromatase inhibitor treatment. Comparison of progression-free survival as assessed by blinded independent central review for gedatolisib triplet versus fulvestrant and gedatolisib doublet versus fulvestrant was the primary objective. RESULTS A total of 392 patients were randomly assigned 1:1:1. The median study follow-up was 10.1 months. The median progression-free survival was 9.3 months in the gedatolisib-triplet group, 2.0 months in the fulvestrant group (hazard ratio [HR] for progression or death, 0.24 [95% CI, 0.17 to 0.35]; P < .001), and 7.4 months in the gedatolisib-doublet group (HR, 0.33 [95% CI, 0.24 to 0.48]; P < .001 v fulvestrant). Grade ≥3 treatment-related adverse events (TRAEs) reported in the gedatolisib-triplet and gedatolisib-doublet groups, respectively, included neutropenia (62.3%, 0.8%), stomatitis (19.2%, 12.3%), rash (4.6%, 5.4%), hyperglycemia (2.3%, 2.3%), and diarrhea (1.5%, 0.8%). Study treatment discontinuation because of TRAEs was reported in 2.3% (triplet) and 3.1% (doublet) of patients. CONCLUSION The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor–positive/HER2−, PIK3CA WT advanced breast cancer.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (158)
Sara A. Hurvitz
Department of Medicine, University of Washington Medicine, Clinical Research Division, Fred Hutchinson Cancer Center, Seattle
Rachel M. Layman
Department of Breast Medical Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA
Giuseppe Curigliano
Fabrice André
Jorge C. Nadal
Miguel Martín
Hyo S. Han
Sarah C. Mutka
Keren Moss
1Dexoligo Therapeutics, Or Akiva, Israel
Sam Suzuki
Brian Sullivan
Arcturus Therapeutics
Igor Gorbatchevsky
Rachel Layman
Robert Wesolowski
Erica Stringer-Reasor
Rena Callahan
Hyo Han
William Irvin
Issam Makhoul
Jennifer Specht
Massimo Cristofanilli
Weill-Cornell Medicine, New York–Presbyterian Hospital, New York
Hiba Jabbour-Aida
DAVID CHAN
University of California, Berkeley, Berkeley, California, United States
Antonio Giordano
Ritesh Parajuli
University of California Irvine Division of Hematology and Oncology, Chao Family Comprehensive Cancer Center, Irvine, CA
Andrea Silber
Hema Vankayala
Delia Guaqueta
Tayyaba Bashir
Gerburg Wulf
Ricardo Alvarez
Sibel Blau
Jennifer Suga
Sunil Babu
6Fort Wayne Medical Oncology & Hematology, Fort Wayne, United States
Amanda Gillespie-Twardy
Kathryn Hudson
Urszula Sobol
Wederson Claudino
Cynthia Osborne
Jose Guimaraes
Danielle Charpentier
Jeffrey Sulpher
Cameron Phillips
Daniel Egle
Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria
Martin Wiesholzer
Renate Pusch
Sonja Heibl
3Austrian Group of Medical Tumor Therapy (AGMT) Study Group, Vienna, Austria
Laure Nuytemans
Francois Duhoux
Patrick Neven
Sevilay Altintas
Nicolas Isambert
Barbara Pistilli
Department of Cancer Medicine, Gustave Roussy, Villejuif, France
Marie Meurer
Monica Arnedos
Youssef Tazi
Frank Priou
George Emile
Christoph Mundhenke
Marcus Schmidt
Max Planck Institute for Chemical Physics of Solids, Nöthnitzer Str. 40, Dresden 01187, Germany
Matthias Hackenthal
Toralf Reimer
Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany
Mustafa Deryal
Caritas Klinikum St. Theresia-Saarbruecken, Center for Gynecology, Saarbrücken, Germany
Joke Tio
Marina Cazzaniga
Phase 1 Research Unit, Fondazione IRCCS San Gerardo, Monza, Italy
Giuseppe Tonini
Marco Angelo Colleoni
Giampaolo Tortora
Laura Biganzoli
Daniela Boggiani
Yann Izarzugaza Peron
Alba Gonzalez-Haba Martinez
Noelia Martinez Janez
Carmela Rodriguez Lopez
Jose Luis Alonso Romero
Santiago Gonzalez Santiago
Agostina Stradella Trucco
Cristina Saavedra Serrano
Sarah Khan
Ciara O’Brien
Simon Waters
Alistair Ring
Davide Mauri
Grigorios Rallis
Kostantinos Papazisis
Flora Zagouri
Alexandra Hospital, Athens, Greece
Rossitza Krasteva
Assia Konsoulova-Kirova
Ivan Shterev Donev
Nadezhda Miteva-Yovcheva
Tomas Buchler
Bohuslav Melichar
Eugen Kubala
Peter Arkosy
Judit Kocsis
Bács-Kiskun Megyei Oktatókórház, Kecskemét, Hungary
Lubomir Bodnar
Ewa Kalinka
Boguslawa Karaszewska
Department of Oncology, Regional Polyclinical Hospital in Konin, Konin, Poland
Zbigniew Nowecki
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie, Warsaw, Poland
Katarzyna Hetman
Aleksandra Grela-Wojewoda
Pratia MCM Krakow, Kraków, Poland
Maciej Studzinski
Barbara Radecka
Patricia Visan
Michael Schenker
Department of Oncology, University of Medicine and Pharmacy of Craiova, Craiova, Romania
Aurelia Alexandru
Alina Amalia Herzal
Nicoleta Zenovia Antone
Andrei Ungureanu
Govind Babu
Hemant Malhotra
Mahatma Gandhi Medical College Hospital, Jaipur, India
Louisa Lo
Catherine Shannon
Mohammed Islam
Junghoon Shin
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
Jee Hung Kim
Sung-Bae Kim
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Su-Jin Koh
Gun Min Kim
Kyong Hwa Park
Valerie Heong
Department of Medical Oncology, Tan Tock Seng Hospital, Singapore, Singapore
Terence Alk Huang Tan
Nan Soon Wong
Lynette Ngo Su-Mien
Liang-Chih Liu
China Medical University Hospital, Taichung, Taiwan
Ling-Ming Tseng
Ming-Feng Hou
Shou-Tung Chen
Yen-Shen Lu
Department of Medical Oncology, National Taiwan University Hospital, Cancer Center Branch
Kuo-Ting Lee
National Cheng Kung University Hospital, Taiwan, China
Jo-Pai Chen
Ernesto Korbenfeld
British Hospital of Buenos Aires, Central British Hospital, Buenos Aires
Guillermo Streich
Geronimo Rosselli
Juan Manuel Puig
Susana Kahl
Juan Jose Rodriguez
Martin Richardet
Cristian Micheri
Matias Salazar
Jorge Carlos Nadal
Alexander Fleming Institute, Buenos Aires, Argentina
Maria Marta Bader
Monica Lis Casalnuovo
Hospital María Curie, Buenos Aires
Laura Testa
Instituto D’Or de Pesquisa e Ensino (IDOR), São Paulo, Brazil
Giuliano Santos Borges
Catarina Pesquisa Clínica - Clínica de Neoplasias Litoral, Santa Catarina, Brazil
Marcelle Goldner Cesca
A.C. Camargo Cancer Center, São Paulo, Brazil
Fabio André Franke
Oncosite-Oncoclínicas, Ijuí, Brazil
Graziela Zibetti Dal Molin
Virginia Braga
Bruno Melo Fernandes
Centro de Pesquisa Oncológica, Belem, Brazil
Marlid Cruz
Ivan Martinez Alvarez
Daniel Motola
Cynthia Villarreal
Mario Sanchez
Eva Willars Inman
Yuly A. Remolina-Bonilla
Jorge Luis Martinez Rodriguez
Filios Alta Medicina, Monterrey, Mexico