Abstract P4-03-30: Patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer
Bibliographic record
Abstract
Abstract Background: Tucatinib is an oral HER2-targeted therapy that was approved by the FDA in April 2020 for use in combination with trastuzumab and capecitabine for treatment of patients with previously treated HER2+ metastatic breast cancer (MBC). In the randomized HER2CLIMB trial median (95% CI) overall survival (mOS) and progression-free survival (PFS) for patients receiving tucatinib with trastuzumab and capecitabine were 21.9 (18.3, 31.0) and 7.8 (7.5, 9.6) months, respectively. HER2CLIMB utilized a placebo + trastuzumab + capecitabine comparator arm and included patients with active and stable brain metastasis (BM). Objectives: Describe patient characteristics, treatment patterns, and clinical outcomes for tucatinib-based treatment in the real-world setting. Methods: This retrospective cohort study included patients treated for HER2+ MBC between January 2017 and March 2022 in the nationwide de-identified electronic health record-derived Flatiron Health Metastatic Breast Cancer database who received tucatinib-based treatment outside of a clinical trial setting. Demographic and clinical characteristics of patients were described at baseline (MBC diagnosis) as well as at initiation of each oncologist-defined, rule-based line of therapy (LOT). Key outcomes included time to next treatment (TTNT), persistence, and mOS. Results: Of 2,057 patients treated for HER2+ MBC in the study period who met the inclusion criteria, 154 received tucatinib-based treatment. Of these patients, 18 (12%), 44 (29%), 33 (21%) and 59 (38%) received tucatinib-based treatment in the first-line (1L), second-line (2L), third-line (3L), and fourth-line or further (4L+) respectively. Median age at MBC diagnosis was 54 years. Median follow-up from tucatinib-based treatment initiation was 8.6 months. Overall, 106 (69%) had BM prior to initiating tucatinib therapy (14 [78%], 37 [84%], 20 [61%], and 35 [59%] in 1L, 2L, 3L, and 4L+ respectively). Those with BM initiated tucatinib-based treatment after a median of 2 prior therapies, compared with 2.5 in the non-BM group. The most common metastatic treatment regimens prior to 2L tucatinib-based treatment were trastuzumab + pertuzumab-based, and the most common regimens immediately following 2L tucatinib-based treatment were trastuzumab-based and trastuzumab deruxtecan. The most common regimens immediately prior to and following 3L tucatinib-based treatment were T-DM1 and trastuzumab deruxtecan, respectively. The median (95% CI) TTNT was 8.4 (6.3, 11.3) months overall, and 12.8 (5.5, not reached [NR]) months, 9.8 (4.8, NR) months, and 9.5 (6.1, 15.3) months in 1L, 2L, and 3L, respectively, the median OS was not reached overall (Table 1). Of patients with sufficient follow-up since treatment initiation, 65% (62/96) remained on tucatinib-based treatment after 6 months and 40% (20/50) after 12 months. Conclusion: The majority of patients receiving tucatinib-based treatment in clinical practice have BM at treatment initiation, constituting a larger proportion of the population than in HER2CLIMB (47.5% of patients). Tucatinib-based treatment use in the real-world setting is associated with a similar mOS and TTNT as in HER2CLIMB. Table 1: Median overall survival and time to next treatment in HER2CLIMB and this study *Time to next treatment was used as a proxy for progression-free survival in the HER2CLIMB clinical trial population. CI, confidence interval; mOS, median overall survival; NR, not reached; TTNT, time to next treatment. Citation Format: Peter A. Kaufman, Edward Neuberger, Ling-I Hsu, Naomi Schwartz, Karen Bartley, Shu Wang, Yutong Liu, Matthew T. Blahna, Brian T. Pittner, Gabriel Wong, Carey Anders. Patient characteristics, treatment patterns, and clinical outcomes associated with tucatinib therapy in HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-30.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".