Camizestrant, a next-generation oral SERD, versus fulvestrant in post-menopausal women with oestrogen receptor-positive, HER2-negative advanced breast cancer (SERENA-2): a multi-dose, open-label, randomised, phase 2 trial.

Autor:	Oliveira M; Medical Oncology Department, Vall d'Hebron University Hospital and Breast Cancer Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain. Electronic address: moliveira@vhio.net., Pominchuk D; Medical Center Verum, Kyiv, Ukraine., Nowecki Z; The Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland., Hamilton E; Sarah Cannon Research Institute, Nashville, TN, USA., Kulyaba Y; Makiivka City Hospital of Donetsk Region, Makiivka, Ukraine., Andabekov T; AV Medical Group, St Petersburg, Russia., Hotko Y; Central City Hospital, Uzhgorod National University, Uzhgorod, Ukraine., Melkadze T; Oncology and Hematology Department, Academician Fridon Todua Medical Center, Research Institute of Clinical Medicine, Tbilisi, Georgia., Nemsadze G; The Institute of Clinical Oncology, Tbilisi, Georgia., Neven P; Multidisciplinary Breast Center, University Hospitals Leuven, Campus Gasthuisberg, Leuven, Belgium., Vladimirov V; Pyatigorsky Oncology Dispensary, Pyatigorsk, Russia., Zamagni C; IRCCS Azienda Ospedaliero-universitaria di Bologna, Bologna, Italy., Denys H; Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium., Forget F; Centre Hospitalier de l'Ardenne-Site de Libramont, Libramont-Chevigny, Belgium., Horvath Z; Center of Oncoradiology, Bács-Kiskun County Teaching Hospital, Kecskemét, Hungary., Nesterova A; Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan, Kazan, Russia., Ajimi M; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK., Kirova B; Oncology Patient Safety, Oncology R&D, AstraZeneca, Cambridge, UK., Klinowska T; Late Development, Oncology R&D, AstraZeneca, Cambridge, UK., Lindemann JPO; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK., Lissa D; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK., Mathewson A; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK., Morrow CJ; Research and Early Development, Oncology R&D, AstraZeneca, Cambridge, UK., Traugottova Z; Parexel International, Prague, Czech Republic., van Zyl R; Parexel International, Bloemfontein, South Africa., Arkania E; Helsicore Israeli Georgian Medical Research Clinic, Tbilisi, Georgia.
Jazyk:	angličtina
Zdroj:	The Lancet. Oncology [Lancet Oncol] 2024 Nov; Vol. 25 (11), pp. 1424-1439.
DOI:	10.1016/S1470-2045(24)00387-5
Abstrakt:	Background: Resistance to endocrine therapies in hormone receptor-positive breast cancer is challenging. We aimed to assess the next-generation oral selective oestrogen receptor degrader (SERD) and complete oestrogen receptor antagonist, camizestrant, versus the first-approved SERD, fulvestrant, in post-menopausal women with oestrogen receptor-positive, HER2-negative, advanced breast cancer. Methods: SERENA-2 is an open-label, randomised, phase 2 trial that is being conducted at 74 study centres across Asia, Europe, the Middle East, and North America. Female patients aged 18 years or older who were post-menopausal with histologically or cytologically confirmed metastastic or locoregional oestrogen receptor-positive, HER2-negative breast cancer, an Eastern Cooperative Oncology Group or WHO performance status of 0 or 1, and disease recurrence or progression on at least one line of endocrine therapy, and no more than one previous endocrine therapy in the advanced setting. Patients were initially randomly assigned (1:1:1:1) to receive oral camizestrant once daily at 75 mg, 150 mg, or 300 mg (until the 300 mg group was closed), or fulvestrant intramuscularly at 500 mg (per label). Randomisation was managed through an interactive web-based system and stratified by previous treatment with CDK4/6 inhibitors and presence of liver and/or lung metastases. The primary objective was to determine clinical efficacy of camizestrant versus fulvestrant at each dose level using the primary endpoint of investigator-assessed progression-free survival, per Response Evaluation Criteria in Solid Tumours (version 1.1), assessed by intention to treat in all randomly assigned patients (full analysis set). No formal statistical comparison for the efficacy analysis of the camizestrant 300 mg dose versus fulvestrant was to be performed. Safety analyses included all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04214288, and is ongoing. Findings: Between May 11, 2020, and Aug 10, 2021, 240 patients were randomly assigned to receive camizestrant 75 mg (n=74), 150 mg (n=73), 300 mg (n=20), or fulvestrant (n=73), and were included in the full analysis set. All patients received at least one dose of study drug. Median follow-up was 16·6 months (IQR 12·9-19·4) for the camizestrant 75 mg group, 16·3 months (12·9-18·3) for the camizestrant 150 mg group, and 14·7 months (12·7-20·1) for the fulvestrant 500 mg group. Median progression-free survival was 7·2 months (90% CI 3·7-10·9) with camizestrant 75 mg, 7·7 months (5·5-12·9) with camizestrant 150 mg, and 3·7 months (2·0-6·0) with fulvestrant. The hazard ratio for camizestrant 75 mg versus fulvestrant was 0·59 (90% CI 0·42-0·82; p=0·017), and the hazard ratio for camizestrant 150 mg versus fulvestrant was 0·64 (0·46-0·89; p=0·0090). Treatment-related adverse events occurred in 39 (53%) of 74 patients in the camizestrant 75 mg group, 49 (67%) of 73 patients in the camizestrant 150 mg group, 14 (70%) of 20 patients in the camizestrant 300 mg group, and 13 (18%) of 73 patients in the fulvestrant group. No single grade 3 or worse treatment-emergent adverse event occurred in more than two (3%) patients in any group. Serious treatment-emergent adverse events occurred in six (8%) patients in the camizestrant 75 mg group, seven (10%) patients in the camizestrant 150 mg group, two (10%) patients in the camizestrant 300 mg group, and four (5%) patients in the fulvestrant group. No treatment-related deaths occurred. Interpretation: Camizestrant at 75 and 150 mg showed a significant benefit in progression-free survival versus fulvestrant. These results support further development of camizestrant for the treatment of oestrogen receptor-positive, HER2-negative breast cancer. Funding: AstraZeneca. Competing Interests: Declaration of interests MO reports institution payments for support on the present manuscript from AstraZeneca; grants from AstraZeneca, Ayala Pharmaceuticals, Boehringer-Ingelheim, Genentech, Gilead, GSK, Novartis, Roche, Seagen, and Zenith Epigenetics; consulting fees from AstraZeneca, Daiichi Sankyo/AstraZeneca, Gilead, iTEOS, Lilly, MSD, Relay Therapeutics, Roche, SeaGen, and Pierre-Fabre; honoraria from AstraZeneca, Eisai, Gilead, Libbs, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, and AstraZeneca Taiwan; fees for meetings or travel from Eisai and Gilead; and other financial or non-financial interests as the head of the SOLTI Breast Cancer Group. EH reports institution payments for support on the present manuscript from AstraZeneca; grants from AbbVie, Accutar Biotechnology, Acerta Pharma, ADC Therapeutics, AKESOBIO Australia, Amgen, Aravive, ArQule, Artios, Arvinas, AtlasMedx, Black Diamond, Bliss BioPharmaceuticals, Boehringer Ingelheim, Cascadian Therapeutics, Clovis, Compugen, Context Therapeutics, Cullen-Florentine, Curis, CytomX, Daiichi Sankyo, Dana Farber Cancer Inst, Dantari, Deciphera, Duality Biologics, eFFECTOR Therapeutics, Ellipses Pharma, Elucida Oncology, EMD Serono, Fochon, FujiFilm, G1 Therapeutics, H3 Biomedicine, Harpoon, Hutchinson MediPharma, Immunogen, Immunomedics, Incyte, Infinity Pharmaceuticals, InvestisBio, Jacobio, Karyopharm, Leap Therapeutics, Lilly, Lycera, Mabspace Biosciences, Macrogenics, MedImmune, Merck, Mersana, Merus, Millennium, Molecular Templates, Myriad Genetic Labratories, Novartis, Nucana, Olema, OncoMed, Onconova Therapeutics, ORIC Pharmaceuticals, Orinove, Pfizer, PharmaMar, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Plexxikon, Radius Health, Regeneron, Relay Therapeutics, Repertoire Immune Medicine, Rgenix, Roche/Genentech, SeaGen, Sermonix Pharmaceuticals, Shattuck Labs, Silverback, StemCentRx, Sutro, Syndax, Syros, Taiho, TapImmune, Tesaro, Tolmar, Torque Therapeutics, Treadwell Therapeutics, Verastem, Vincerx Pharma, Zenith Epigenetics, and Zymeworks; and consulting fees from Arcus, Arvinas, AstraZeneca, Black Diamond, Boehringer Ingelheim, CytomX, Daiichi Sankyo, Dantari, Deciphera Pharmaceuticals, Eisai, Ellipses Pharma, Greenwich Lifesciences, H3 Biomedicine, iTeos, Janssen, Lilly, Loxo, Merck, Mersana, Novartis, Orum Therapeutics, Pfizer, Propella Therapeutics, Puma Biotechnology, Relay Therapeutics, Roche/Genentech, SeaGen, Stemline Therapeutics, Silverback Therapeutics, and Verascity Science. PN reports institution payments for support on the present manuscript from AstraZeneca; grants from Sanofi; consulting fees paid to institution from Hoffman/La Roche, AstraZeneca, Lilly, Novartis, Pfizer, Pierre Fabre, Radius Health, Roche, and Teva; fees for meetings or travel from Lilly, Pfizer, Roche, AstraZeneca, Novartis, and Hoffmann/La Roche; and other financial or non-financial interests as Chair BIG-SENO VVOG Steering committee member of MONARCH-2 and MONARCH-E, SERENA-2 external advisory role for the reimbursement committee, and commission of personalised medicine of Belgian Government. CZ reports institution payments for support on the present manuscript from AstraZeneca; grants from Novartis, consulting fees from AstraZeneca, Daiichi-Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, and Seagen; honoraria from AstraZeneca, Gilead, Novartis, Roche, Pfizer, Lilly, MSD, Eisai, and GSK; fees for meetings or travel from Roche, Novartis, Pfizer, Lilly, AstraZeneca, MSD, Eisai, GSK, ExactSciences, and Clovis; and participation on a data monitoring committee or advisory board for Roche Novartis, Pfizer, Lilly, AstraZeneca, MSD, Eisai, GSK, and Daiichi Sankyo. HD reports institution payments for support on the present manuscript from AstraZeneca; consulting fees from Pfizer, Roche, PharmaMar, AstraZeneca, Eli Lilly, Novartis, Amgen, GSK, MSD, Seagen, and Gilead; honoraria from PharmaMar, AstraZeneca, Eli Lilly, Novartis, Amgen, GSK, MSD, Teva, Seagen, and Gilead; honoraria received by institution from Pfizer and Roche; and fees for meetings or travel from Pfizer, Roche, PharmaMar, Teva, AstraZeneca, MSD, GSK, and Gilead. ZH reports institution payments for support on the present manuscript from AstraZeneca and lecture fees. ZT and RvZ are employees of Parexel and report institution payments for support on the present manuscript from AstraZeneca. DP, ZN, YK, TA, YH, TM, GN, VV, AN, and EA report institution payments for support on the present manuscript from AstraZeneca. MA, BK, TK, JPOL, DL, AM, and CJM are employees of AstraZeneca and own stock or stock options. FF declares no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu