203P Clinical effectiveness of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer (mBC) by ER expression level: Subgroup analysis from phase IIIb LUCY trial
Bibliographic record
Abstract
In the OlympiAD phase III trial, olaparib significantly prolonged progression-free survival (PFS) vs chemotherapy in patients (pts) with germline-BRCA-mutated (gBRCAm), HER2-negative mBC regardless of hormone receptor (HR) status. In a study population that reflects clinical practice, the phase IIIb LUCY trial similarly showed clinical effectiveness of olaparib regardless of HR status. ASCO/CAP guidelines highlight the lack of data on the best treatment approach for breast tumors that are estrogen receptor (ER)-low (1–10% ER+ stained cells). We examined olaparib clinical effectiveness by ER expression in pts with HER2-negative gBRCAm mBC from the LUCY trial. In this open-label trial, pts with germline or somatic BRCAm, HER2-negative mBC received olaparib (300 mg BID). Pts had received ≤2 chemotherapy lines for mBC and a taxane and/or anthracycline in the (neo)adjuvant or mBC setting. Pts with ER+ BC had received endocrine therapy. In this post hoc subgroup analysis (data cut-off Sept 1, 2021), pts with gBRCAm were grouped by ER expression (ER <1%; 1–10%; >10% by IHC) and analysed for PFS, overall survival, clinical response rate (CRR; i.e. the proportion of pts assessed as responding by the investigator [radiological or symptomatic] at ≥1 visit), and duration of clinical response. 251/252 pts in the gBRCAm cohort were included (ER <1% n=117; 1–10% n=29; >10% n=105). At baseline, pts in the ER <1% group had shorter median times from their original diagnosis (29.7 vs 52.0 vs 58.6 mo) and from diagnosis of mBC (4.8 vs 11.1 vs 12.5 mo) vs pts in the ER 1–10% and >10% groups, respectively. Efficacy outcomes with olaparib were consistent across ER expression subgroups (Table).Table: 203PEfficacy results by ER expressionER <1%ER 1–10%ER >10%Median PFS, months (95% CI)92/117*6.8 (5.5–9.0)24/29*8.3 (4.5–12.6)89/105*8.4 (7.6–11.0)Median OS, months (95% CI)67/117*20.1 (16.5–26.9)20/29*22.9 (13.0–35.1)54/105*27.4 (23.0–NR)CRR, % (95% CI)59/116*50.9 (41.4–60.3)12/28*42.9 (24.5–62.8)51/104*49.0 (39.1–59.0)Median DOCR, months (IQR)59/116*8.3 (3.8–26.5)12/28*7.2 (5.3–14.1)51/104*7.4 (4.3–17.7)∗number of events or responses/number of evaluable pts.CI, confidence interval; CRR, clinical response rate; DOCR, duration of clinical response; IQR, interquartile range; NR, not reached; OS, overall survival; PFS, progression-free survival. Open table in a new tab ∗number of events or responses/number of evaluable pts. CI, confidence interval; CRR, clinical response rate; DOCR, duration of clinical response; IQR, interquartile range; NR, not reached; OS, overall survival; PFS, progression-free survival. Real-world results of the phase IIIb LUCY trial support the clinical effectiveness of olaparib in pts with gBRCAm, HER2-negative mBC, regardless of ER expression level.
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| 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) | 0.002 | 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".