Cancer de l’ovaire avancé : raisonnement sur le traitement d’entretien HRD/BRCA en première ligne
Chapitre d'apprentissage déterministe sur les entités KB d'OpenOnco, les cas synthétiques et les dossiers sources.
Objectifs d'apprentissage
- Identify the histology, germline/tumor BRCA, HRD status, and platinum-response inputs needed before first-line ovarian-cancer maintenance selection.
- Expliquez pourquoi l'induction à base de platine est la première ligne dorsale universelle et comment BRCA / HRD statut route le choix d'entretien entre olaparib, niraparib et bevacizumab et l'observation.
- Reconnaître les obligations parallèles — qualité chirurgicale-débulking, dépistage des infections, risque VTE et exposition préalable à PARP — qui modifient le plan d'entretien sans modifier la colonne vertébrale cytotoxique.
En un coup d'oeil
- High-grade serous histology, germline + tumor BRCA1/2, and HRD assay status are required before any first-line maintenance plan.
- Carboplatin + paclitaxel is the universal cytotoxic backbone; the maintenance decision sits on top of the platinum response.
- Les voies d'accès à l'entretien de l'olaparib (SOLO-1) comme première option canonique de la maladie mutante BRCA; la maladie non-BRCA HRD positive tire le niraparib/olaparib dans la conversation.
- Suboptimal debulking, prior PARP-inhibitor exposure, and active platinum resistance change the conversation more than HRD score alone.
- This chapter is an OpenOnco-authored learning aid, not official ESMO content or a CME-credit activity.
Diagnostic et biomarqueur minimum
Before any first-line plan in advanced ovarian cancer the chapter expects confirmed high-grade serous (or otherwise platinum-sensitive) histology, complete germline BRCA1/2 testing, tumor BRCA1/2 testing where the germline result is negative, an HRD assay result interpreted alongside the assay caveat (different vendors, different cut-offs), a documented debulking outcome (R0 vs R1 vs R2 / interval), and baseline organ function. The chapter is explicit that HRD status without BRCA context is incomplete because the routing of olaparib, niraparib, and bevacizumab depends on the combination.
Entités liées
DIS-OVARIANCarcinome ovarienmaladiesBIO-BRCA1-BRCA2-GERMLINEmutation de Germline BRCA1/BRCA2biomarqueursBIO-HRD-STATUSHRD statusbiomarqueursTEST-GERMLINE-BRCA-PANELGermline BRCA1/2 + séquençage des panneaux HRRessaisRF-BREAST-OVARIAN-HRD-ASSAY-DISTINCTIONHRD assay platform mismatch in breast or ovarian cancer: HRD-positive call by Myriad myChoice CDx (composite Genomic Instability Score GIS = LOH + TAI + LST, threshold ≥42) is NOT interchangeable with HRD-positive by FoundationOne CDx HRD (LOH-high ≥16% genomic LOH + BRCA1/2 status, no TAI / LST). The two FDA-approved companion diagnostics use different scoring systems and have ~10-15% discordance in head-to-head series; clinical-trial regimen approvals are platform-locked: olaparib + bevacizumab maintenance in advanced ovarian (PAOLA-1, Ray-Coquard NEJM 2019) is FDA-indicated only on Myriad GIS-based HRD; niraparib monotherapy maintenance (PRIMA, González-Martín NEJM 2019) is also Myriad-validated. F1CDx HRD-high has no companion-diagnostic indication in ovarian PARPi maintenance — using F1CDx LOH-high to indicate olaparib + bev or niraparib is off-label / extrapolated. Action: when an HRD result is reported, identify the assay platform; if F1CDx is the only HRD source and ovarian PARPi-maintenance is being considered, recommend Myriad myChoice reflex (or BRCA1/2 germline+somatic confirmation as fall-back).
Flags rougesSources des sections
SRC-NCCN-OVARIAN-2025Cancer ovarien du NCCNSRC-ESMO-OVARIAN-2024ESMO Guide de pratique clinique du cancer ovarien
Induction et fenêtre de réponse au platine
Carboplatin + paclitaxel remains the universal cytotoxic backbone for first-line advanced ovarian cancer in the OpenOnco model. The maintenance decision is made when the patient completes induction and the platinum response is established. Patients who do not respond to platinum re-enter a different algorithm and do not benefit from PARP-inhibitor maintenance in the canonical first-line model. Bevacizumab can begin during induction and continue into maintenance — the chapter is explicit that bevacizumab and PARP inhibitors are not mutually exclusive, particularly for HRD-positive non-BRCA disease.
Entités liées
ALGO-OVARIAN-ADVANCED-1LALGO-OVARIAN-ADVANCED-1LalgorithmesIND-OVARIAN-ADVANCED-1L-CARBO-PACLI-HRD-NEGIND-OVARIAN-ADVANCED-1L-CARBO-PACLI-HRD-NEGIndicationsIND-OVARIAN-ADVANCED-1L-CARBO-PACLI-HRD-OLAPIND-OVARIAN-ADVANCED-1L-CARBO-PACLI-HRD-OLAPIndicationsREG-CARBO-PACLI-OVARIANCarboplatin + Paclitaxel (ovarian 3-weekly)schémasREG-BEV-MAINTENANCE-OVARIANEntretien du bevacizumab (après 1L de platine, ovar/fallope/péritonéal primaire)schémasSources des sections
SRC-NCCN-OVARIAN-2025Cancer ovarien du NCCNSRC-PRIMA-GONZALEZ-MARTIN-2019Niraparib chez les patients atteints d'un cancer de l'ovaire avancé récemment diagnostiqué
Maintenance routing by BRCA + HRD
Après la réponse au platine, OpenOnco effectue les choix d'entretien par le statut combiné BRCA/HRD. La maladie mutante BRCA (germine ou somatique) mène à l'entretien de l'olaparib comme première option canonique (SOLO-1). La maladie HRD positive non BRCA tire le niraparib (PRIMA) et les combinaisons d'olaparib dans la conversation, souvent avec bevacizumab a continué depuis l'induction. La maladie HRD négative sans mutation BRCA repose habituellement sur le maintien ou l'observation du bevacizumab; le chapitre est explicite que l'ajout d'un inhibiteur PARP à la maladie HRD négative non BRCA n'est pas le défaut canonique.
Entités liées
IND-OVARIAN-MAINT-PARPI-BRCAM-OLAPARIBIND-OVARIAN-MAINT-PARPI-BRCAM-OLAPARIBIndicationsIND-OVARIAN-MAINT-PARPI-HRD-NIRAPARIBIND-OVARIAN-MAINT-PARPI-HRD-NIRAPARIBIndicationsIND-OVARIAN-MAINT-BEVIND-OVARIAN-MAINT-BEVIndicationsREG-OLAPARIB-MAINT-OVARIANMaintien de l'olaparib (réponse ovarienne post-platine HRD+)schémasREG-NIRAPARIB-MAINT-OVARIANMaintien du niraparib (HRD+ récurrent sensible au platine ovarien, NOVA / PRIMA)schémasRF-OVARIAN-BRCA-MUT-ACTIONABLEBRCA1 or BRCA2 pathogenic variant (germline OR somatic) in high-grade serous ovarian carcinoma — ~20-25% prevalence (15% germline + ~7% somatic). Olaparib maintenance after platinum-based 1L (SOLO-1 — mPFS 56.0 vs 13.8 mo BRCA-mut) is treatment-defining; rucaparib + niraparib alternatives. SOLO-2 — 2L+ relapse maintenance.
Flags rougesRF-OVARIAN-HRD-POSITIVE-ACTIONABLEHomologous Recombination Deficiency (HRD)-positive high-grade serous ovarian carcinoma (BRCA1/2 mutation OR Genomic Instability Score ≥42). PARPi maintenance after platinum-based induction is treatment-defining: niraparib (PRIMA — mPFS 21.9 vs 10.4 mo HRD-pos), olaparib + bevacizumab (PAOLA-1 — mPFS 37.2 vs 17.7 mo HRD-pos).
Flags rougesSources des sections
SRC-SOLO1-MOORE-2018Maintien Olaparib chez les patients présentant un cancer de l'ovaire avancé récemment diagnostiquéSRC-PRIMA-GONZALEZ-MARTIN-2019Niraparib chez les patients atteints d'un cancer de l'ovaire avancé récemment diagnostiqué
Trappes communes
Do not treat the maintenance decision as a single biomarker call. HRD-assay vendor differences and cut-off thresholds change which patients fall on each side of the line — the chapter expects the learner to record which assay was used and to read the report holistically. Suboptimal debulking changes the prognosis but does not by itself remove a PARP-inhibitor option. Prior PARP-inhibitor exposure (rare at first line, common at recurrence) reshapes the maintenance discussion completely. VTE risk and infection screening sit beside the regimen choice and must not be skipped.
Entités liées
RF-OVARIAN-SUBOPTIMAL-DEBULKINGChirurgie cytoréductrice primaire sous-optimale (maladie résiduelle ≥1 cm) ou non résécable lors de la présentation dans des essais de carcinome ovarien avancé (FIGO III-IV). Déclencheur de MDT pour la chimiothérapie néoadjuvante (NACT) → voie de débulking d'intervalle (IDS) par CHORUS / EORTC55971, plutôt que de débolissement primaire.
Flags rougesRF-OVARIAN-HRD-ACTIONABILITYHRD-positive (BRCA1/2 mutation OR Genomic Instability Score ≥42) high-grade serous ovarian carcinoma. Treatment-defining for PARPi maintenance after platinum-based induction. Olaparib (SOLO-1 BRCA-only, PAOLA-1 with bev) + niraparib (PRIMA all-comer) substantially improve PFS in HRD-positive subset.
Flags rougesRF-BREAST-OVARIAN-HRD-ASSAY-DISTINCTIONHRD assay platform mismatch in breast or ovarian cancer: HRD-positive call by Myriad myChoice CDx (composite Genomic Instability Score GIS = LOH + TAI + LST, threshold ≥42) is NOT interchangeable with HRD-positive by FoundationOne CDx HRD (LOH-high ≥16% genomic LOH + BRCA1/2 status, no TAI / LST). The two FDA-approved companion diagnostics use different scoring systems and have ~10-15% discordance in head-to-head series; clinical-trial regimen approvals are platform-locked: olaparib + bevacizumab maintenance in advanced ovarian (PAOLA-1, Ray-Coquard NEJM 2019) is FDA-indicated only on Myriad GIS-based HRD; niraparib monotherapy maintenance (PRIMA, González-Martín NEJM 2019) is also Myriad-validated. F1CDx HRD-high has no companion-diagnostic indication in ovarian PARPi maintenance — using F1CDx LOH-high to indicate olaparib + bev or niraparib is off-label / extrapolated. Action: when an HRD result is reported, identify the assay platform; if F1CDx is the only HRD source and ovarian PARPi-maintenance is being considered, recommend Myriad myChoice reflex (or BRCA1/2 germline+somatic confirmation as fall-back).
Flags rougesSources des sections
SRC-NCCN-OVARIAN-2025Cancer ovarien du NCCNSRC-ESMO-OVARIAN-2024ESMO Guide de pratique clinique du cancer ovarien
Cas synthétiques travaillés
patient_ovarian_advanced_hrdCancer ovarien avancé HRD positif : raisonnement de maintien - HRD-driven maintenance routing, platinum-response gating examples/patient_ovarian_advanced_hrd.jsonpatient_ovarian_hrd_neg_carbo_pacli_no_parpiHRD-negative ovarian cancer: induction without PARP maintenance - negative-HRD pathway, bevacizumab-only or observation examples/patient_ovarian_hrd_neg_carbo_pacli_no_parpi.json
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