Abstract P1-17-08: Efficacy of lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive metastatic breast cancer: A systematic review and meta- analysis
Bibliographic record
Abstract
Abstract Background: Brain metastases contribute to significant morbidity and mortality in breast cancer. Approximately one fourth of breast tumors overexpress the human epidermal growth factor receptor 2 (HER2) protein and are twice as likely to develop brain metastases. There are currently no systemic therapies approved. We undertook a systematic review and pooled analysis of trials to determine the efficacy of lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive metastatic breast cancer (MBC). Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts through December 31, 2016. Trials that utilized lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive MBC were incorporated in the analysis. The pooled estimated rates were calculated using random effects model. Heterogeneity was assessed using I2 statistic. Results: A total of 513 patients with brain metastases from HER-2 positive MBC from 6 trials and a subgroup of another 4 trials were included in our analysis. Lapatinib and capecitabine therapy was used as second-line treatment in 9 studies (n= 468) and as first-line treatment in the LANDSCAPE study (n= 45). Three studies were retrospective evaluations of randomized trials and the rest were phase 2 trials. CNS objective response rate (ORR) was 26% (95% CI: 19 – 33, I2: 65.9%). Complete response (CR) rate was 1% (95% CI: 0 - 2, I2: 0.0%) and partial response (PR) rate was noted at 24% (95% CI: 17- 31, I2: 66.1%). Stable disease (SD) occurred in 37% (95% CI: 29- 45, I2: 66.6%) and progressive disease (PD) in 19% (95% CI: 12- 25, I2: 66.5%). The first line LANDSCAPE study had the highest PR (49%) and ORR (53%) without a significant impact on CR rate; PD was 7%. Conclusion: Brain metastases in breast cancer is an area of urgent unmet need. Our meta-analysis showed that lapatinib/capecitabine therapy had some first line or second line activity in brain metastases from HER-2 positive MBC. Nevertheless, further randomized controlled trials are required in this patient population. Citation Format: Thein KZ, Zaw MH, Yendala R, Igid HP, Chai-Adisaksopha C, Hardwicke F, Awasthi S, Radhi S. Efficacy of lapatinib and capecitabine combination therapy in brain metastases from HER-2 positive metastatic breast cancer: A systematic review and meta- analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-17-08.
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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 | 0.011 | 0.024 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.019 | 0.037 |
| Bibliometrics | 0.007 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".