دورية أكاديمية
Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial.
| العنوان: | Atezolizumab and chemotherapy for advanced or recurrent endometrial cancer (AtTEnd): a randomised, double-blind, placebo-controlled, phase 3 trial. |
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| المؤلفون: | Colombo N; European Institute of Oncology IRCCS, Milan, Italy; University of Milan-Bicocca, Milan, Italy., Biagioli E; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. Electronic address: elena.biagioli@marionegri.it., Harano K; Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Galli F; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy., Hudson E; Velindre Cancer Centre, Cardiff, UK., Antill Y; Peninsula Health, Monash University, Melbourne, VIC, Australia., Choi CH; Department of Obstetrics and Gynecology, Samsung Seoul Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea., Rabaglio M; Department of Medical Oncology, Inselspital, University Hospital Bern, Bern, Switzerland., Marmé F; Obstetrics and Gynecology, Section Gynecologic Oncology, Universitaetsklinikum Mannheim Medizinische Fakultaet, Mannheim, Germany., Marth C; Department of Obstetrics and Gynecology, Medical University Innsbruck, Innsbruck, Austria., Parma G; European Institute of Oncology IRCCS, Milan, Italy., Fariñas-Madrid L; Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain., Nishio S; Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan., Allan K; Glasgow Oncology Clinical Trials Unit, University of Glasgow, Glasgow, UK., Lee YC; NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia., Piovano E; AOU Città della Salute e della Scienza di Torino - Presidio Sant'Anna, Torino, Italy., Pardo B; Department of Medical Oncology, Catalan Institute of Oncology, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain., Nakagawa S; Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan., McQueen J; Glasgow Oncology Clinical Trials Unit, University of Glasgow, Glasgow, UK., Zamagni C; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Manso L; Hospital 12 de Octubre, Madrid, Spain., Takehara K; Department of Gynecology, NHO Shikoku Cancer Center, Matsuyama, Japan., Tasca G; UOC Oncologia 2 IRCCS Istituto Oncologico Veneto - Padova, Padova, Italy., Ferrero A; Academic Division Obstetrics and Gynaecology, Mauriziano Hospital, University Department of Surgical Sciences, Torino, Italy., Tognon G; UO Ostetricia-Ginecologia ASST Spedali Civili, Università degli Studi-Brescia, Brescia, Italy., Lissoni AA; UOS Oncologia Ginecologica Medica, Università degli Studi di Milano Bicocca, IRCCS San Gerardo dei Tintori - Monza, Monza, Italy., Petrella M; SOD Oncologia Medica Ginecologica, Azienda Ospedaliera Universitaria Careggi, Florence, Italy., Laudani ME; AOU Città della Salute e della Scienza di Torino - Presidio Sant'Anna, Torino, Italy., Rulli E; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy., Uggeri S; Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy., Barretina Ginesta MP; Medical Oncology, Institut Català d'Oncologia & IDIBGI, Girona, Spain. |
| مؤلفون مشاركون: | AtTEnd study group |
| المصدر: | The Lancet. Oncology [Lancet Oncol] 2024 Aug 02. Date of Electronic Publication: 2024 Aug 02. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lancet Pub. Group Country of Publication: England NLM ID: 100957246 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-5488 (Electronic) Linking ISSN: 14702045 NLM ISO Abbreviation: Lancet Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Lancet Pub. Group, c2000- |
| مستخلص: | Background: At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population. Methods: AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0-2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m 2 intravenously on day 1 every 21 days) for 6-8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184. Findings: Between Oct 3, 2018, and Jan 7, 2022, 551 patients were randomly assigned to atezolizumab (n=362) or placebo (n=189). Two patients in the atezolizumab group were excluded from all analyses due to lack of consent. Median follow-up was 28·3 months (IQR 21·2-37·6). 81 (23%) patients in the atezolizumab group and 44 (23%) patients in the placebo group had dMMR disease by central assessment. In the dMMR population, median progression-free survival was not estimable (95% CI 12·4 months-not estimable [NE]) in the atezolizumab group and 6·9 months (6·3-10·1) in the placebo group (hazard ratio [HR] 0·36, 95% CI 0·23-0·57; p=0·0005). In the overall population, median progression-free survival was 10·1 months (95% CI 9·5-12·3) in the atezolizumab group and 8·9 months (8·1-9·6) in the placebo group (HR 0·74, 95% CI 0·61-0·91; p=0·022). Median overall survival was 38·7 months (95% CI 30·6-NE) in the atezolizumab group and 30·2 months (25·0-37·2) in the placebo group (HR 0·82, 95% CI 0·63-1·07; log-rank p=0·048). The p value for the interim analysis of overall survival did not cross the stopping boundary; therefore, the trial will continue until the required number of events are recorded. The most common grade 3-4 adverse events were neutropenia (97 [27%] of 356 patients in the atezolizumab group vs 51 [28%] of 185 in the placebo group) and anaemia (49 [14%] vs 24 [13%]). Treatment-related serious adverse events occurred in 46 (13%) patients in the atezolizumab group and six (3%) patients in the placebo group. Treatment-related deaths occurred in two patients (pneumonia in one patient in each group). Interpretation: Atezolizumab plus chemotherapy increased progression-free survival in patients with advanced or recurrent endometrial carcinoma, particularly in those with dMMR carcinomas, suggesting the addition of atezolizumab to standard chemotherapy as first-line treatment in this specific subgroup. Funding: F Hoffmann-La Roche. Competing Interests: Declaration of interests EB, FG, ER, and SU report grants from Roche to their institution to support the conduct of the study. NC reports personal fees from AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Mersana, MSD/Merck, Nuvation Bio, OncXerna, Pieris, Pfizer, Roche, and Novocure; and grants or research support from GSK and AstraZeneca. KH reports personal fees from AstraZeneca, Chugai, Eisai, MSD/Merck, Taiho, and Takeda; and grants or research support from MSD/Merck, Chugai, Takeda, AstraZeneca, and Daiichi Sankyo. EH reports personal fees from GSK and Clovis. FM reports personal fees from Roche, Eisai, Novartis, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, MSD/Merck, GSK, Clovis, Gilead, Myriad Genetics, Seagen, and Stemline Menarini; grants or research support from Roche; and participation on data safety monitoring or advisory boards for Immutep, Amgen, and Palleos Healthcare. CM reports personal fees from Roche, Novartis, MSD/Merck, AstraZeneca, Pfizer, PharmaMar, ImmunoGen, Daiichi Sankyo, Novocure, BioNTtech, Eisai, and GSK. LF-M reports personal fees from AstraZeneca, GSK, MSD/Merck, Eisai, and Pharma&. YCL reports personal fees from AstraZeneca, and grants or research support from BeiGene. EP reports personal fees from GSK and AstraZeneca. BP reports personal fees from AstraZeneca, GSK, MSD/Merck, and Pharma&. CZ reports personal fees from Roche, Eisai, Novartis, AstraZeneca, Pfizer, QuintilesIMS, Clovis, Eli Lilly, Istituto Gentili, Daiichi Sankyo, Seagen, MSD/Merck, GSK, and Gilead; and grants or research support from Roche, Novartis, AstraZeneca, Pfizer, Eisai, Clovis, Gilead, Seagen, Eli Lilly, Daiichi Sankyo, and MSD/Merck. KT reports personal fees from AstraZeneca, Chugai Pharma, Takeda, MSD/Merck, Nippon Kayaku, Eisai, and Sanofi; and grants or research support from Chugai Pharma. AF reports personal fees from GSK, AstraZeneca, and MSD/Merck. MP reports personal fees from AstraZeneca, Eisai, GSK, and MSD/Merck. MPBG reports personal fees from AstraZeneca, GSK, MSD/Merck, PharmaMar, Clovis Oncology, Eisai, Pharma&, and Kyowa Kirin; and a leadership role for Geico. All other authors declare no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.) |
| فهرسة مساهمة: | Investigator: P Zola; C Casanova; V Arcangeli; L Antonuzzo; A Gadducci; S Cosio; A Clamp; M Persic; I McNeish; L Tookman; A Redondo Sanchez; CH Choi; E Baldini; I Palaia; P Benedetti Panici; N Takahashi; J Lombard; A Ardizzoia; A Bologna; AM Herrero Ibáñez; A Musolino; R Márquez Vázquez; K Pietzner; E Braicu; VA Heinzelmann-Schwarz; M Powell; Y Yokoyama; S Baron-Hay; C Abeni; C Martin Lorente; JF Cueva; F Trillsch; F Heitz; B Ataseven; E Petru; M Heubner; AH Sadozye; S Dubey; A Tazbirkova; S Tiley; K Chrystal; SW Kim; M Fehr; K Scatchard; A Anand; A Taylor; H Watary; T Enomoto; K Yoshihara; S Selva-Nayagam; B Karki; M Harrison; K Wilkinson; J Goh; A Glasgow; L Chantrill; C Lee; A Bertolini; F Narducci; G Bellotti; V Fusco; S Aebi; M Del Grande; I Colombo; H Tokunaga; S Shigeta; G Goss; ZR Siow; C Steer; H Lin; KB Lee; G Di Meglio; E Massa; E De Marino; V Tortora; I Palacio Vazquez; K Tsuji; E Tominaga; J Goh; A Black; KA So; DH Suh; KH Lee; YM Kim; R Fossati; L Carlucci; M Barberis; V Torri; A Santoni |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03603184 |
| تواريخ الأحداث: | Date Created: 20240805 Latest Revision: 20240805 |
| رمز التحديث: | 20240806 |
| DOI: | 10.1016/S1470-2045(24)00334-6 |
| PMID: | 39102832 |
| قاعدة البيانات: | MEDLINE |
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