180O IMpassion132 double-blind randomised phase III trial of chemotherapy (CT) ± atezolizumab (atezo) for early-relapsing unresectable locally advanced or metastatic triple-negative breast cancer (aTNBC)
Bibliographic record
Abstract
Immune checkpoint inhibitors (ICIs) improve efficacy of first-line CT for some patients (pts) with aTNBC but data in early relapse are limited. IMpassion132 (NCT03371017) enrolled pts with aTNBC relapsing <12 mo after the last of any anthracycline- and taxane-containing (neo)adjuvant CT or primary TNBC surgery. PD-L1 status was centrally assessed by SP142 before randomisation. Initially pts were enrolled irrespective of PD-L1 status. In Aug 2019 the protocol was amended to enrich for PD-L1+ (tumour immune cell ≥1%) aTNBC. Stratification factors were investigator-selected CT (capecitabine 1000 mg/m2 bid d1–14 q21d [X] or carboplatin AUC2 + gemcitabine 1000 mg/m2 d1 & 8 q21d [CG]), visceral (lung and/or liver) metastases and (until Aug 2019) PD-L1 status. Pts were randomised 1:1 to placebo or atezo 1200 mg q21d with chosen CT until progression or unacceptable toxicity. Crossover was not allowed. The primary endpoint was overall survival (OS), tested hierarchically first in PD-L1+ pts then, if positive, in the modified intent-to-treat (mITT*) population. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Among 354 PD-L1+ pts (of 595 pts enrolled), 68% had a disease-free interval <6 mo and 73% received CG. The primary objective was not met (Table); subgroup results were consistent. PFS was similar across treatment arms and populations (median ∼4 mo). ORRs were 28% with placebo + CT vs 40% with atezo + CT. Adverse events (predominantly haematological) were broadly similar between arms and as expected with atezo + CG or X in early-relapsing aTNBC.Table: 180OFinal OS analysis (prespecified after ∼247 deaths in the PD-L1+ population); median follow-up 9 monthsOS (95% CI)PD-L1+mITT*Placebo + CT (n=177)Atezo + CT (n=177)Placebo + CT (n=192)Atezo + CT (n=188)Events, n (%)128 (72)124 (70)160 (83)158 (84)Stratified hazard ratio0.93 (0.73–1.20); p=0.590.94 (0.76–1.18)Median, mo11.2 (9.0–13.3)12.1 (10.1–15.1)9.8 (8.4–12.0)10.4 (8.9–12.9)12-mo rate, %48 (40–55)50 (43–58)42 (35–50)46 (39–54)18-mo rate, %32 (25–40)34 (26–41)26 (19–32)27 (20–34)*All-comer pts randomised before Aug 2019. Open table in a new tab *All-comer pts randomised before Aug 2019. Pts with early-relapsing aTNBC have a dismal prognosis that is not improved with atezo.A biology-based definition of intrinsic resistance to ICIs in aTNBC is urgently needed to optimally treat these pts and design next-generation (combination) clinical trials.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".