Evaluation of novel hormonal agents in metastatic castration-resistant prostate cancer using real-world data in Quebec
Bibliographic record
Abstract
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
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.013 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.007 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".