MITO END-3: efficacy of Avelumab immunotherapy according to molecular profiling in first line endometrial cancer therapy
| العنوان: | MITO END-3: efficacy of Avelumab immunotherapy according to molecular profiling in first line endometrial cancer therapy |
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| المؤلفون: | Sandro Pignata, Daniela Califano, Domenica Lorusso, Laura Arenare, Michele Bartoletti, Ugo De Giorgi, Claudia Andreetta, Carmela Pisano, Giovanni Scambia, Davide Lombardi, Alberto Farolfi, Saverio Cinieri, Anna Passarelli, Vanda Salutari, Carmine De Angelis, Chiara Mignogna, Domenico Priolo, Ettore Domenico Capoluongo, Stefano Tamberi, Giovanni Luca Scaglione, Valentina Arcangeli, Rossella De Cecio, Giosuè Scognamiglio, Filippo Greco, Anna Spina, Margherita Turinetto, Daniela Russo, Vittoria Carbone, Chiara Casartelli, Clorinda Schettino, Francesco Perrone |
| سنة النشر: | 2023 |
| المجموعة: | Zenodo |
| مصطلحات موضوعية: | Endometrial cancer, immunotherapy, molecular profiling |
| الوصف: | Immunotherapy combined to chemotherapy significantly improves progression free survival compared to first line chemotherapy alone in advanced endometrial cancer, with a much larger effect size in microsatellite-instability high (MSI-H) cases. New biomarkers might help to select patients that may have benefit among those with a microsatellite-stable (MSS) tumor. Methods. In a pre-planned translational analysis of the MITO END-3 trial we assessed the significance of genomic abnormalities in patients randomized to standard carboplatin/paclitaxel without or with avelumab. Results. Out of 125 randomized patients, 109 had samples eligible for Next Generation Sequencing (NGS) analysis and 102 had MSI tested. According to The Cancer Genome Atlas (TCGA) there were 29 cases MSI-H, 26 MSS TP53 wild type (wt), 47 MSS TP53 mutated (mut), and one case with POLE mutation. Four mutated genes were present in more than 30 % of cases: TP53, PIK3CA, ARID1A, PTEN. Eleven patients (10 %) had a BRCA 1/2 mutation (5 in MSI-H and 6 in MSS). High TMB (≥ 10Muts/Mb) was observed in all MSI-H patients, in 4 out of 47 MSS/TP53mut, and in no case in the MSS/TP53wt category. The effect of avelumab on progression-free survival (PFS) significantly varied according to TCGA categories, being favorable in MSI-H and worst in MSS/TP53mut (P interaction=0.003); a similar non-significant trend was seen in survival analysis. ARID1A and PTEN also showed a statistically significant interaction with treatment effect, that was better in presence of the mutation (ARID1A P interaction=0.01; PTEN P interaction=0.002). Conclusion The MITO END-3 trial results suggest that TP53 mutation is associated with poor effect of avelumab, while mutations of PTEN and ARID1A are related to a positive effect of the drug in patients with advanced endometrial cancer. |
| نوع الوثيقة: | dataset |
| اللغة: | English |
| العلاقة: | https://zenodo.org/record/8134241Test; https://doi.org/10.5281/zenodo.8134241Test; oai:zenodo.org:8134241 |
| DOI: | 10.5281/zenodo.8134241 |
| الإتاحة: | https://doi.org/10.5281/zenodo.8134241Test https://doi.org/10.5281/zenodo.8134240Test https://zenodo.org/record/8134241Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.502A51AC |
| قاعدة البيانات: | BASE |
| DOI: | 10.5281/zenodo.8134241 |
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