Sequence decision making for cabazitaxel (Cbz) versus abiraterone (Abt) or enzalutamide (Enz) post-docetaxel (Dtx) in a publicly funded health care system.
Bibliographic record
Abstract
57 Background: The TROPIC trial demonstrated an overall survival (OS) benefit of Cbz after Dtx in metastatic castrate-resistant prostate cancer (mCRPC). However, the novel anti-androgens (NAA) Abi and Enz have demonstrated similar improvements post-Dtx. The recent CARD trial suggests Cbz may provide the greatest OS benefit in selected patients who were rapid progressors ( < 12 months, RP) on first NAA, however Cbz use and efficacy in the real-world is uncertain. We sought to quantify the real-world use of Cbz and evaluate outcomes post-Dtx. Methods: mCRPC patients who received Dtx at the two tertiary referral centres in the Canadian province of Alberta from October 2012 (Cbz funding approval) to December 31st 2017 were assessed. We examined Cbz eligibility per TROPIC and CARD trial criteria, tracked therapies received, and documented objective and subjective reasoning for therapeutic decisions. OS was measured using the Kaplan-Meier method and the log-rank test was used to compare outcomes. The Chi-Square test was used to compare relative therapy utilization. Results: 463 mCRPC patients received Dtx over the study period, including 83 (18%) for castrate sensitive disease. At Dtx progression, 262 patients (56%) were eligible for Cbz per TROPIC trial criteria, while only 162 (62%) of those were RP on first NAA. Post-Dtx OS was lower among TROPIC-eligible patients receiving Cbz compared to those receiving Abi or Enz (9.1 vs 14.2 months, p = 0.001). This OS difference was not demonstrated among RP patients (11.2 vs 12 months, p = 0.664). The most common reasons for TROPIC ineligibility were Dtx intolerance (13%), serious comorbidities (12%), unacceptable blood counts (11%), performance status (9%) or, for CARD ineligible patients, no progression within 12 months on first NAA (38%). The most common agent immediately post-Dtx was Abi (n = 180, 39%), followed by Enz (n = 129, 28%). Significantly fewer patients (n = 56, 12%) received Cbz immediately post-Dtx (p = 0.001), and 149 (32%) received Cbz overall. First line post-Dtx, 286 patients (62%) did not have a documented discussion about Cbz, and in 172 cases (38%) consideration of Cbz was never documented. Patient choice against Cbz chemotherapy was recorded in 15% of discussions. Conclusions: In a real-world cohort of mCRPC patients, Cbz was a significantly less common choice than Abi or Enz after progression on Dtx. In a majority of these cases, no first line discussion of Cbz was documented, and in documented discussions, patient choice was the driving factor in a minority. OS post-Dtx in patients who met TROPIC trial criteria was lower for those receiving Cbz, noting that, unlike in TROPIC, these patients also received NAAs. This OS difference was not seen in those who also progressed rapidly on first NAA. These data suggest ongoing hesitation towards Cbz use in mCRPC and support careful selection of patients who may obtain benefit.
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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 | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".