Evaluation of novel hormonal agents in metastatic castration-resistant prostate cancer using real-world data in Quebec
Notice bibliographique
Résumé
In Canadian men, prostate cancer is the most commonly diagnosed cancer and has very high survival rates. However, a subset of patients will go on to develop an advanced and fatal form of the disease called metastatic castration-resistant prostate cancer (mCRPC). In the past decade, several new drugs with demonstrated survival benefits in clinical trials were approved. Among these newly approved treatments, two of them are novel hormonal agents (NHAs) and have been used widely: abiraterone and enzalutamide. Despite the prevalent use of abiraterone and enzalutamide in mCRPC, many questions still remain unanswered. The overarching aim of this thesis was to generate real-world evidence concerning current knowledge gaps regarding abiraterone and enzalutamide in mCRPC by examining the use and outcomes of these NHAs in the real-world.In the first manuscript, the primary analyses sought to characterize the temporal patterns (2011-2016) of individuals initiating NHAs, categorized by their chemotherapy history (chemotherapy-naïve or post-chemotherapy) and the specialty of the prescribing physician (medical oncology, urology, or other specialties). While most patients were post-chemotherapy NHA initiators in 2012, this proportion decreased over time and accounted for only 13% of NHA initiators by the end of 2016. Medical oncologists were the most frequent prescribers of NHAs (upwards of 60%) throughout 2012 but fell to 45% by the end of 2016. Conversely, the proportion of prescriptions by urologists increased from 22% in 2012 to 42% in 2016. In summary, these findings suggests that the introduction of NHAs may have changed that the care pathways for mCRPC as urologists are increasingly prescribing the NHAs.In the second manuscript, the objective was to assess the comparative cardiovascular safety of abiraterone and enzalutamide in patients with mCRPC in the real-world. First-time NHA users of abiraterone and enzalutamide between 2011 and 2016 were compared. The primary outcome of interest was cardiovascular-related hospitalization. Abiraterone initiators were at greater risk of cardiovascular-related hospitalization compared to enzalutamide initiators (HR 1.82; 95% confidence interval (95%CI) 1.09-3.05). When analyzing the individual subcomponents of the cardiovascular-related hospitalization, the risk of hospitalization for heart failure was greater in abiraterone initiators (HR 2.88; 95%CI 1.09-7.63) compared to enzalutamide users. These results provide clinicians with additional insight on the cardiovascular risks of mCRPC patients treated with NHAs in the real-world and further large studies are required to corroborate these findings.In the third manuscript, the objective was to assess the association between the incidence of NHA-related complications and prescribing specialty in mCRPC patients treated with NHAs. First-time NHA users were grouped by their prescribing specialty (medical oncology (MO) vs urology (URO) vs other (OTH)). Outcomes of interest were overall NHA-related complications and its subtypes: cardiovascular, metabolic, infectious and general/non-specific. For overall NHA-related complications, the URO group (HR 0.97, 95%CI 0.72-1.31) and OTH group (HR 1.05, 95%CI 0.70-1.54) were not different compared to the MO group. While the URO group was associated with a greater incidence of cardiovascular complications compared to the MO group (HR 1.85, 95%CI 1.04-3.28), it was also at lower risk of infectious complications (HR 0.66, 95%CI 0.43-0.98). The results demonstrate the need for greater awareness in mCRPC clinical guidelines regarding management of NHA-related complications and drives the call to further promote multidisciplinary care in order to optimize patient outcomes.Overall, this thesis provides additional data to understand how the NHAs, abiraterone and enzalutamide, are being used for mCRPC in clinical practice in Quebec and their outcomes
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,013 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,002 | 0,007 |
| Études des sciences et des technologies | 0,002 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».