Incidence, management, and resolution of noninfectious pneumonitis in BOLERO-2.
Bibliographic record
Abstract
561 Background: The BOLERO-2 trial showed that adding everolimus (EVE) to exemestane (EXE) more than doubled progression-free survival (PFS) without reducing quality of life versus placebo (PBO) + EXE alone in postmenopausal women with hormone-receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC) progressing on/after nonsteroidal aromatase inhibitor (NSAI) therapy. Although generally well tolerated, mTOR inhibitors such as EVE have been associated with noninfectious pneumonitis (NIP). Methods: Patients (pts) were randomized 2:1 to receive EVE+EXE or PBO+EXE. Incidence and severity of NIP, consequent dose interruptions/adjustments, study drug discontinuations, and time to resolution were recorded. Results: Median duration of exposure to EVE was 24 weeks with median dose intensity of 8.6 mg/d. Pulmonary adverse events (AEs) of any grade (NIP, interstitial lung disease, lung infiltration, pneumonia, or pulmonary fibrosis) were recorded in 97 of 482 pts (20%) in the EVE+EXE arm versus 1 of 238 pts (<1%) in the PBO+EXE arm. Of these, 16% of pts (77 of 482) in the EVE+EXE arm versus 0 in the PBO+EXE arm had a diagnosis consistent with NIP. In the EVE+EXE arm, grade 1 (no symptoms), grade 2 and 3 NIP occurred in 7%, 6% and 3% of pts, respectively, and no grade 4 events were reported. Complete resolution of NIP to grade ≤1 was recorded for all but 4 pts for whom NIP was still observed at last follow-up before study discontinuation. Overall, in the EVE+EXE arm, NIP was recorded as the reason for dose interruption and treatment discontinuation in 7.5% and 5.6% of pts, respectively. Conclusions: Data from BOLERO-2 support the combination of EVE and EXE to significantly prolong PFS in postmenopausal women with HR+, HER2– ABC progressing on/after NSAI. The incidence of NIP in this study was generally consistent with reports from other oncology settings, was of mild to moderate severity, and was generally reversible with appropriate interventions and temporary dose modifications. Patient and healthcare provider education for early diagnosis and management of NIP are highly recommended. Clinical trial information: NCT00863655.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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 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".