Practice Patterns and Outcomes of Novel Targeted Agents for the Treatment of <i>ERBB2</i>-Positive Metastatic Breast Cancer
Bibliographic record
Abstract
Importance: Clinical trials have shown that the addition of pertuzumab to trastuzumab-based chemotherapy for first-line treatment of ERBB2-positive metastatic breast cancer is associated with considerable improvement in overall survival (OS). In the second-line setting, trastuzumab emtansine (T-DM1) improves OS compared with capecitabine/lapatinib in patients previously treated with trastuzumab-based chemotherapy. However, there are few data describing long-term real-world outcomes with these agents. Objective: To describe practice patterns and outcomes associated with pertuzumab and T-DM1 in routine clinical practice. Design, Setting, and Participants: This population-based retrospective cohort study used the Ontario Cancer Registry linked to electronic treatment databases to identify all patients treated with pertuzumab and T-DM1 following reimbursement approval in Ontario, Canada, which has a single-payer public health system. Participants included women with stage IV ERBB2-positive metastatic breast cancer receiving treatment with pertuzumab for first-line metastatic indication from December 2013 through December 2017, and those treated with T-DM1 from May 2014 through December 2017. Pertuzumab and T-DM1 cohorts were analyzed separately. Data were analyzed December 2019 to December 2020. Exposures: Treatment with pertuzumab or T-DM1. Main Outcomes and Measures: The primary outcome was OS, determined using the Kaplan-Meier method. Factors associated with OS were identified using a Cox proportional hazard model. Results: The median (interquartile range [IQR]) age of the 795 women who received pertuzumab and 506 women who received T-DM1 was 57 (49-67) and 56 (48-66) years, respectively. Among the cohort of patients who received pertuzumab, the median (IQR) OS and time on treatment was 43 (16.2-unavailable) and 14 (6.0-26.2) months, respectively. In the T-DM1 cohort, the proportion of pertuzumab-naive patients decreased over time from 68 of 91 [74.7%] in 2014 to 16 of 89 [18.0%] in 2017 (P < .001). The median (IQR) OS and time on treatment was 15 (6.7-27.7) and 4 (1.4-9.0) months, respectively. Median OS was shorter for patients with prior pertuzumab treatment than in the pertuzumab-naive subgroup (12 vs 19 months; adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = .004). Conclusions and Relevance: In this population-based cohort study, the survival of patients treated with pertuzumab and T-DM1 in routine practice appeared inferior to results from pivotal clinical trials. Differences in outcome likely reflect differences in patient population and previous lines of therapy in routine practice. Further work is needed to understand the effectiveness of T-DM1 after pertuzumab exposure.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".