Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial
| العنوان: | Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial |
|---|---|
| المؤلفون: | Sandro Pignata, Giovanni Scambia, Clorinda Schettino, Laura Arenare, Carmela Pisano, Davide Lombardi, Ugo De Giorgi, Claudia Andreetta, Saverio Cinieri, Carmine De Angelis, Domenico Priolo, Claudia Casanova, Marta Rosati, Filippo Greco, Elena Zafarana, Ilaria Schiavetto, Serafina Mammoliti, Sabrina Chiara Cecere, Vanda Salutari, Simona Scalone, Alberto Farolfi, Marilena Di Napoli, Domenica Lorusso, Piera Gargiulo, Daniela Califano, Daniela Russo, Anna Spina, Rossella De Cecio, Paolo Chiodini, Francesco Perrone, Valentina Accinno, Chiara Altavilla, Giovanna Antonelli, Grazia Artioli, Francesco Avola, Bonifacio Barbara, Valentina Barbato, Michele Bartoletti, Simona Bevilacqua, Roberto Bordonaro, Oriana Borghese, Gaetano Buonfanti, Floriana Camarda, Giuliana Canzanella, Vittoria Carbone, Maria Rita Carbone, Giulia Carlo Stella, Chiara Cassani, Fabrizio Castagna, Monica Cattaneo, Margherita Cinefra, Nicoletta Colombo, Serena Corsetti, Monia Dall'Agata, Maria D'Amico, Gennaro Daniele, Elvira De Marino, Giovanni De Matteis, Sabino De Placido, Gabriella Del Bene, Antonia Del Giudice, Francesca Del Monte, Michele Del Sesto, Maddalena Donini, Giuliana Drudi, Gianluca Falcone, Adolfo Favaretto, Giulia Ferrera, Manuela Florio, Valeria Forestieri, Maria Stella Gallo, Ciro Gallo, Francesca Garibaldi, Fabiana Gerevini, Viola Ghizzoni, Maria Olga Giganti, Anna Gimigliano, Elena Giudice, Nicoletta Gnocchi, Adriano Gravina, Stefano Greggi, Maria Laura Iaia, Annalisa Ilardi, Gelsomina Iovine, Gabriella Ippoliti, Giulia Irollo, Ilenia Isidori, Mariateresa Lapresa, Giuseppe Lavenia, Laura Longhitano, Bortot Lucia, Gabriella Luzi, Sara Mariano, Valentina Marino, Giovanna Marrapese, Marilena Martino, Roberta Matocci, Enrica Mazzoni, Daniela Mercuri, Maria Mirto, Giovanna Mollo, Abbondanza Montinaro, Marta Moscatelli, Anna Maria Mosconi, Lucia Musacchio, Nicoletta Nanni, Pamela Natalucci, Milena Sabrina Nicoloso, Michele Orditura, Gabriella Maria Parma, Rodolfo Passalacqua, Michela Pelone, Maria Teresa Perri, Bruno Perrucci, Alessandra Piancastelli, Maria Carmela Piccirillo, Antonio Piccolo, Stefania Rapisardi, Giorgia Ravaglia, Teresa Ribecco, Caterina Ricci, Marianna Roccio, Fiorella Romano, Daniela Sambataro, Alfonso Savio, Ada Sbriglia, Cono Scaffa, Concetta Sergi, Francesca Sgandurra, Roberto Sorio, Stefano Stabile, Gianna Tabaro, Margherita Tambaro, Stefano Tamberi, Angelica Tecchiato, Angela Maria Trujillo, Eleonora Zaccarelli |
| المساهمون: | Pignata, S, Scambia, G, Schettino, C, Arenare, L, Pisano, C, Lombardi, D, De Giorgi, U, Andreetta, C, Cinieri, S, De Angelis, C, Priolo, D, Casanova, C, Rosati, M, Greco, F, Zafarana, E, Schiavetto, I, Mammoliti, S, Cecere, S, Salutari, V, Scalone, S, Farolfi, A, Di Napoli, M, Lorusso, D, Gargiulo, P, Califano, D, Russo, D, Spina, A, De Cecio, R, Chiodini, P, Perrone, F, Accinno, V, Altavilla, C, Antonelli, G, Artioli, G, Avola, F, Barbara, B, Barbato, V, Bartoletti, M, Bevilacqua, S, Bordonaro, R, Borghese, O, Buonfanti, G, Camarda, F, Canzanella, G, Carbone, V, Carbone, M, Carlo Stella, G, Cassani, C, Castagna, F, Cattaneo, M, Cinefra, M, Colombo, N, Corsetti, S, Dall'Agata, M, D'Amico, M, Daniele, G, De Marino, E, De Matteis, G, De Placido, S, Del Bene, G, Del Giudice, A, Del Monte, F, Del Sesto, M, Donini, M, Drudi, G, Falcone, G, Favaretto, A, Ferrera, G, Florio, M, Forestieri, V, Gallo, M, Gallo, C, Garibaldi, F, Gerevini, F, Ghizzoni, V, Giganti, M, Gimigliano, A, Giudice, E, Gnocchi, N, Gravina, A, Greggi, S, Iaia, M, Ilardi, A, Iovine, G, Ippoliti, G, Irollo, G, Isidori, I, Lapresa, M, Lavenia, G, Longhitano, L, Lucia, B, Luzi, G, Mariano, S, Marino, V, Marrapese, G, Martino, M, Matocci, R, Mazzoni, E, Mercuri, D, Mirto, M |
| المصدر: | The Lancet Oncology. 24:286-296 |
| بيانات النشر: | Elsevier BV, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Oncology, Carboplatin |
| الوصف: | Background: Adding immunotherapy to first-line chemotherapy might improve outcomes for patients with advanced or recurrent endometrial cancer. We aimed to compare carboplatin and paclitaxel versus avelumab plus carboplatin and paclitaxel as first-line treatment with avelumab given concurrent to chemotherapy and as maintenance after the end of chemotherapy. Methods: MITO END-3 is an open-label, randomised, controlled, phase 2 trial conducted at 31 cancer institutes, hospitals, and universities in Italy. Eligible patients were aged 18 years or older with histologically confirmed advanced (FIGO stage III–IV) or recurrent endometrial cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and no previous systemic anticancer therapy as primary treatment for advanced or metastatic disease. Participants were randomly assigned (1:1) using a computerised minimisation procedure stratified by centre, histology, and stage at study entry, to either receive carboplatin (area under the curve [AUC] 5 mg/mL × min) and paclitaxel (175 mg/m2; standard group) intravenously every 3 weeks for six to eight cycles or avelumab (10 mg/kg intravenously) added to carboplatin and paclitaxel (experimental group) every 3 weeks and then every 2 weeks as a single maintenance treatment after the end of chemotherapy until disease progression or unacceptable toxicity. Patients, treating clinicians, and those assessing radiological examinations were not masked to study treatment. The primary endpoint was investigator-assessed progression-free survival, measured in the intention-to-treat (ITT) population. Patients who received at least one dose of study drug were included in the safety analysis. Experimental group superiority was tested with 80% power and one-tailed α 0·20. This trial is registered with ClinicalTrials.gov (NCT03503786) and EudraCT (2016–004403–31). Findings: From April 9, 2018, to May 13, 2021, 166 women were assessed for eligibility and 39 were excluded. 125 eligible patients were randomly assigned to receive carboplatin and paclitaxel (n=62) or avelumab plus carboplatin and paclitaxel (n=63) and included in the ITT population. The median follow-up was 23·3 months (IQR 13·2–29·6) and was similar between the two groups. 91 progression-free survival events were reported, with 49 events in 62 patients in the standard group and 42 events in 63 patients in the experimental group. The median progression-free survival was 9·9 months (95% CI 6·7–12·1) in the standard group and 9·6 months (7·2–17·7) in the experimental group (HR of progression or death 0·78 [60% CI 0·65–0·93]; one-tailed p=0·085). Serious adverse events were reported more frequently in the experimental group (24 vs seven events in the standard group); neutrophil count decrease was the most frequent grade 3–4 adverse event (19 [31%] of 61 patients in the experimental group vs 26 [43%] of 61 patients in the standard group). Two deaths occurred in the experimental group during treatment (one respiratory failure following severe myositis [possibly related to treatment] and one cardiac arrest [not related to treatment]). Interpretation: Adding avelumab to first-line chemotherapy deserves further testing in patients with advanced or recurrent endometrial cancer, although consideration of mismatch repair status is warranted. |
| وصف الملف: | STAMPA |
| تدمد: | 1470-2045 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2431afb32030e7d11f084ebe105f6204Test https://doi.org/10.1016/s1470-2045Test(23)00016-5 |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....2431afb32030e7d11f084ebe105f6204 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14702045 |
|---|