Predictors of prolonged benefit from palbociclib (PAL) plus fulvestrant (F) in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer (ABC) in PALOMA-3.
Bibliographic record
Abstract
1050 Background: PAL+F improved progression-free survival (PFS) over F + placebo (P) in patients (pts) with endocrine-resistant HR+/HER2– ABC. We examined factors predictive of long-term benefit on PAL+F. Methods: Pre/postmenopausal pts with HR+/HER2– ABC that progressed on prior endocrine therapy (ET) were randomized 2:1 to PAL (125 mg/d oral [3 wk on, 1 wk off]) + F (500 mg) or P+F. Characteristics of pts with prolonged benefit (treatment [tx] duration ≥18 mo for PAL+F; ≥12 mo for P+F based on median PFS and tx duration) were compared with the intent-to-treat (ITT) population. Results: PAL+F improved PFS vs P+F (11.2 vs 4.6 mo; hazard ratio, 0.50). By Aug 2016, 138 pts had long-term benefit: 100/347 (29%) pts on PAL+F received tx for ≥18 mo, including 70 (20%) who received > 2 y (26–39 cycles). In contrast, 38/174 (22%) pts on P+F received ≥12 mo of tx; only 16 (9%) received > 2 y (27–38 cycles). No apparent differences in baseline characteristics of pts with long-term benefit were observed between groups except that a greater proportion of those on P+F had a single site of disease involvement (40% PAL+F vs 63% P+F). Pts with long-term benefit on PAL+F had lower rates of visceral disease (42% vs 60%), liver metastases (18% vs 40%), and ≥3 disease sites (27% vs 39%) at baseline vs the ITT population; no difference in sensitivity to prior ET was observed (84% vs 79%). Objective response rate (ORR) was higher among pts with prolonged benefit on PAL+F vs ITT (36% vs 26%). Conclusions: PAL+F is associated with prolonged benefit in about a third of pts treated with the combination in PALOMA-3. These pts achieve higher ORR compared to other study pts and the benefit is independent of baseline site and number of metastatic recurrences and prior endocrine sensitivity. Benefit from F alone is less prolonged and appears limited to those with 1 site of disease involvement. The analysis confirms the efficacy of PAL+F in HR+ ABC with visceral recurrence. Biomarker analyses are ongoing in pts with long-term benefit to understand molecular features predictive of tx sensitivity. Funding: Pfizer. Clinical trial information: NCT01942135.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.004 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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".