Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial
| Autor: | Capoluongo ED, B, Pellegrino, Arenare L, Califano D, Scambia G, L, Beltrame, V, Serra, Scaglione GL, Spina A, Cecere SC, De Cecio R, N, Normanno, N, Colombo, Lorusso D, Russo D, Nardelli C, M, D'Incalci, Llop-Guevara A, Pisano C, G, Baldassarre, Mezzanzanica D, Artioli G, Setaro M, Tasca G, C, Roma, Campanini N, Cinieri S, A, Sergi, Musolino A, Perrone F, Chiodini P, S, Marchini, Pignata S |
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| Přispěvatelé: | Institut Català de la Salut, [Capoluongo ED] Department of Molecular Medicine and Medical Biotechnology, Università degli Studi di Napoli Federico II, Naples, Italy. Azienda Ospedaliera per L'Emergenza, Cannizzaro, Catania, Italy. [Pellegrino B] Department of Medicine and Surgery, University of Parma, Parma, Italy. Medical Oncology and Breast Unit, University Hospital of Parma, Parma, Italy. Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC), Parma, Italy. [Arenare L] Clinical Trial Unit, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Naples, Italy. [Califano D] Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS – Fondazione G. Pascale, Naples, Italy. [Scambia G] Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Department of Life Science and Public Health, Catholic University of Sacred Heart Largo Agostino Gemelli, Rome, Italy. [Beltrame L] Molecular Pharmacology laboratory, Group of Cancer Pharmacology IRCCS Humanitas Research Hospital, Rozzano, Italy. [Serra V, Guevara A] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Capoluongo, E, Pellegrino, B, Arenare, L, Califano, D, Scambia, G, Beltrame, L, Serra, V, Scaglione, G, Spina, A, Cecere, S, De Cecio, R, Normanno, N, Colombo, N, Lorusso, D, Russo, D, Nardelli, C, D'Incalci, M, Llop-Guevara, A, Pisano, C, Baldassarre, G, Mezzanzanica, D, Artioli, G, Setaro, M, Tasca, G, Roma, C, Campanini, N, Cinieri, S, Sergi, A, Musolino, A, Perrone, F, Chiodini, P, Marchini, S, Pignata, S, Capoluongo, E D, Scaglione, G L, Cecere, S C |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Cancer Research
Paclitaxel Genetic Phenomena::Recombination Genetic::Homologous Recombination [PHENOMENA AND PROCESSES] Ovaris - Càncer - Aspectes genètics neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas [ENFERMEDADES] Carboplatin Other subheadings::Other subheadings::/genetics [Other subheadings] Humans Homologous Recombination Recombinació genètica Platinum fenómenos genéticos::recombinación genética::recombinación homóloga [FENÓMENOS Y PROCESOS] Ovarian Neoplasms Mangifera molecular testing Otros calificadores::Otros calificadores::/genética [Otros calificadores] Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms [DISEASES] RD HRR Myriad ovarian cancer Ovaris - Càncer - Tractament Bevacizumab Oncology HRD Female Poly(ADP-ribose) Polymerases |
| Zdroj: | Scientia |
| Popis: | Molecular testing; Ovarian cancer Proves moleculars; Càncer d'ovaris Pruebas moleculares; Cáncer de ovarios Background The detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms. Patients and methods Two academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD. One hundred patients with high-grade OC enrolled in the MITO16A/MaNGO-OV2 trial and treated with first-line therapy with carboplatin, paclitaxel, and bevacizumab were analyzed. Results The failure rate of the two genomic assays was 2%. The sensitivity in detecting HRD when compared with Myriad was 98.1% and 90.6%, respectively. The agreement rate with Myriad was 0.92 and 0.87, with a Cohen’s κ coefficient corresponding to 0.84 and 0.74, respectively. For the RAD51 foci assay, the failure rate was 30%. When the test was successful, discordant results for deficient and proficient tumors were observed, and additional HRD patients were identified compared to Myriad; sensitivity was 82.9%, agreement rate was 0.65, and Cohen’s κ coefficient was 0.18. The HRD detected by genomic assays and residual tumor at primary surgery and stage was correlated with progression-free survival at multivariate analysis. Conclusions Results suggest the feasibility of academic tests for assessing HRD status that show robust concordance with Myriad and correlation with clinical outcome. The contribution of the functional information related to the RAD51 foci test to the genomic data needs further investigation. This work was supported by funding from the AIRC [grant numbers IG 2016 – ID. 18921 and IG 2021 – ID. 25932 projects – P.I. SP and CO-2018-12367051 (Ministero della Salute) P.I SP]; Ricerca Corrente grant M2/7 from Ministero della Salute to DC, Ricerca Corrente from Ministero della Salute to SP. SM is supported by the Italian Association for Cancer Research [grant number IG-2017 n: IG19997]. MITO16A/MaNGO-OV2 trial was partially supported by Roche. AL is a recipient of a grant from the Asociación Española contra el Cáncer (AECC) [grant number INVES20095LLOP]. VS is a recipient of a grant from the Instituto de Salud Carlos III [grant number CPII19/00033] and a European grant for personalized medicine [grant number ERAPERMED 2019-215]. BP is a recipient of a grant from GOIRC. BP was supported by ESMO with a Clinical Translational Fellowship aid supported by Roche. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the authors and do not necessarily reflect those of ESMO or Roche. NC has received funding from AstraZeneca (to the institution). FP has received funding from Roche, AstraZeneca, Pfizer, Merck Sharp & Dome, Bayer, Incyte, Taiho Oncology, Janssen Cilag, Exelixis, Aileron, and Daiichi Sankyo (grants to the institution for clinical trial activities). |
| Databáze: | OpenAIRE |
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