A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108).
Bibliographic record
Abstract
LBA2 Background: About 6% of newly diagnosed breast cancer patients present with Stage IV disease and an intact primary tumor (IPT). Locoregional treatment (LRT) for the IPT is hypothesized to improve survival based on retrospective analyses, but randomized trials have provided conflicting data. We now report the results of E2108, a Phase 3 trial that examined the worth of LRT for the IPT following initial systemic therapy. Methods: Stage IV patients with IPT were registered, treated with optimal systemic therapy (OST) based on patient and tumor characteristics; those who did not progress during 4-8 months of OST were randomized to LRT for the IPT, or no LRT. The primary endpoint was overall survival (OS), with locoregional disease control as a secondary endpoint. Stratified log rank test and Cox proportional hazard model were used to compare OS between treatment groups. Cumulative incidence of locoregional recurrence/progression was estimated and Gray test was used for treatment group comparisons. The trial was designed to detect an improvement in 3 year OS rate from 30% with OST alone to 49.3% for OST+LRT (power 95%, 1-sided alpha 0.05) with full information expected after 152 deaths; the data monitoring committee recommended data release after 80% of full information. Results: 390 patients were enrolled between 2/8/11 and 7/23/15, and received OST. Of these, 256 eligible patients were randomized to either continued OST alone (N = 131) or OST+LRT (N = 125).There were 121 deaths and 43 locoregional progression events after a median follow up 59 months (range: 0-91). There was no significant difference in OS (3-year OS rate 68.4% in OST+LRT vs. 67.9% OST alone arm, stratified log-rank p = 0.63, HR = 1.09, 90% CI: 0.80, 1.49) or in progression-free survival (p = 0.40). The locoregional recurrence/progression was significantly higher in the OST alone arm (3-year rate 25.6% vs 10.2%, Gray test p = 0.003). Health-related quality of life (HRQOL) measured by FACT-B Trial Outcome Index was significantly worse in the OST+LRT arm than OST alone arm at 18 months post randomization (60% completion, Wilcoxon rank sum test p = 0.01), but no difference was observed at time points 6 months (74% completion) or 30 months (56% completion). Conclusions: Early local therapy does not improve survival in patients with de novo metastatic breast cancer and an IPT. Although there was a 2.5-fold higher risk of local disease progression without LRT, LRT of the IPT did not lead to improved HRQOL. Clinical trial information: NCT01242800 .
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 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 | 0.007 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".