دورية أكاديمية
Prospective high-throughput genome profiling of advanced cancers: results of the PERMED-01 clinical trial
| العنوان: | Prospective high-throughput genome profiling of advanced cancers: results of the PERMED-01 clinical trial |
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| المؤلفون: | François Bertucci, Anthony Gonçalves, Arnaud Guille, José Adelaïde, Séverine Garnier, Nadine Carbuccia, Emilien Billon, Pascal Finetti, Patrick Sfumato, Audrey Monneur, Christophe Pécheux, Martin Khran, Serge Brunelle, Lenaïg Mescam, Jeanne Thomassin-Piana, Flora Poizat, Emmanuelle Charafe-Jauffret, Olivier Turrini, Eric Lambaudie, Magali Provansal, Jean-Marc Extra, Anne Madroszyk, Marine Gilabert, Renaud Sabatier, Cécile Vicier, Emilie Mamessier, Christian Chabannon, Jihane Pakradouni, Patrice Viens, Fabrice André, Gwenaelle Gravis, Cornel Popovici, Daniel Birnbaum, Max Chaffanet |
| المصدر: | Genome Medicine, Vol 13, Iss 1, Pp 1-20 (2021) |
| بيانات النشر: | BMC |
| سنة النشر: | 2021 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | aCGH, Advanced cancers, Mutation, PERMED-01 trial, Precision medicine, Sequencing, Medicine, Genetics, QH426-470 |
| الوصف: | Background The benefit of precision medicine based on relatively limited gene sets and often-archived samples remains unproven. PERMED-01 (NCT02342158) was a prospective monocentric clinical trial assessing, in adults with advanced solid cancer, the feasibility and impact of extensive molecular profiling applied to newly biopsied tumor sample and based on targeted NGS (t-NGS) of the largest gene panel to date and whole-genome array-comparative genomic hybridization (aCGH) with assessment of single-gene alterations and clinically relevant genomic scores. Methods Eligible patients with refractory cancer had one tumor lesion accessible to biopsy. Extracted tumor DNA was profiled by t-NGS and aCGH. We assessed alterations of 802 “candidate cancer” genes and global genomic scores, such as homologous recombination deficiency (HRD) score and tumor mutational burden. The primary endpoint was the number of patients with actionable genetic alterations (AGAs). Secondary endpoints herein reported included a description of patients with AGA who received a “matched therapy” and their clinical outcome, and a comparison of AGA identification with t-NGS and aCGH versus whole-exome sequencing (WES). Results Between November 2014 and September 2019, we enrolled 550 patients heavily pretreated. An exploitable complete molecular profile was obtained in 441/550 patients (80%). At least one AGA, defined in real time by our molecular tumor board, was found in 393/550 patients (71%, two-sided 90%CI 68–75%). Only 94/550 patients (17%, 95%CI 14–21) received an “AGA-matched therapy” on progression. The most frequent AGAs leading to “matched therapy” included PIK3CA mutations, KRAS mutations/amplifications, PTEN deletions/mutations, ERBB2 amplifications/mutations, and BRCA1/2 mutations. Such “matched therapy” improved by at least 1.3-fold the progression-free survival on matched therapy (PFS2) compared to PFS on prior therapy (PFS1) in 36% of cases, representing 6% of the enrolled patients. Within patients with AGA treated on ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1756-994X |
| العلاقة: | https://doi.org/10.1186/s13073-021-00897-9Test; https://doaj.org/toc/1756-994XTest; https://doaj.org/article/685cee8dc4e4477fb464978bcebb91ffTest |
| DOI: | 10.1186/s13073-021-00897-9 |
| الإتاحة: | https://doi.org/10.1186/s13073-021-00897-9Test https://doaj.org/article/685cee8dc4e4477fb464978bcebb91ffTest |
| رقم الانضمام: | edsbas.C12AD595 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 1756994X |
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| DOI: | 10.1186/s13073-021-00897-9 |