Abstract P1-19-16: Long-term pooled safety analysis of palbociclib in combination with endocrine therapy for hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer: An updated analysis
Bibliographic record
Abstract
Abstract Background Palbociclib (PAL) in combination with endocrine therapy (ET) was shown to be tolerable in a previous pooled analysis of the 3 PALOMA clinical trials. This new pooled, post hoc analysis examines the safety profile of PAL + ET using data from more recent data cutoff dates with longer drug exposure. Methods Data were pooled from 3 randomized phase 2 and 3 studies of patients with hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2- ABC). Postmenopausal first-line patients were randomized to receive letrozole (2.5 mg/d, continuously) +/- PAL (125 mg/d, 3/1 schedule) in PALOMA-1 or letrozole (2.5 mg/d, continuously) + PAL (125 mg/d, 3/1 schedule)/placebo in PALOMA-2. In PALOMA-3, pre/peri- and postmenopausal patients with prior endocrine resistance received intramuscular fulvestrant (500 mg every 14 days for the first 3 injections, then every 28 days) + PAL (125 mg/d, 3/1 schedule)/placebo. The cumulative rates of adverse events (AEs) were assessed over time. Results Updated data cutoff dates used for this analysis were December 21, 2017 (PALOMA-1), May 31, 2017 (PALOMA-2), and April 13, 2018 (PALOMA-3). The total number of person-years of exposure was 1950 (1422 PAL + ET, 528 ET). In the ET arm (n=471), 20.2% of patients were treated for ≥24 months and 10.2% were treated for ≥36 months. In the PAL + ET arm (n=872), 36% of patients were treated for ≥24 months and 22.4% for ≥36 months. The majority of patients treated for ≥24 and ≥36 months in the PAL + ET arm were from PALOMA-2. As expected, neutropenia and infections (any grade) were more frequent with PAL + ET (82.1% and 59.2%, respectively) than in the ET arm (5.1% and 39.5%). Febrile neutropenia was reported in 1.4% of patients in the PAL + ET arm. The incidence of hematologic AEs in the PAL + ET arm peaked during the first year of treatment and then plateaued over the subsequent 5 years. Serious AEs were reported in 22.8% of patients in the PAL + ET arm and 15.5% in the ET arm. Selected cumulative grade 3/4 event rates through 5 years were neutropenia (68.3% in PAL + ET; 0.8% in ET), leukopenia (29.9%; 0.2%), infections (6.4%; 2.8%), anemia (5.3%; 2.1%), fatigue (2.9%; 1.3%), alanine aminotransferase increased (2.2%; 0.2%), aspartate aminotransferase increased (2.9%; 1.3%), diarrhea (1%; 1.1%), nausea (0.6%; 1.3%), vomiting (0.7%; 1.1%), and QTc prolongation (0.3%; 0.2%). After adjusting for treatment exposure, incidence rates of venous thromboembolism and pulmonary embolism were 0.0225 (PAL + ET) and 0.0246 (ET) per person-year and 0.0127 (PAL + ET) and 0.0132 (ET) per person-year, respectively. Conclusion This 5-year, long-term safety analysis of PAL + ET showed a consistent profile with no new safety signals, and no cumulative/delayed toxicities. PAL + ET remains a safe and manageable treatment for patients with HR+/HER2- ABC. Pfizer (NCT00721409, NCT01740427, NCT01942135) Citation Format: Richard S Finn, Hope S Rugo, Karen Gelmon, Massimo Cristofanilli, Marco Colleoni, Sherene Loi, Patrick Schnell, Dongrui R Lu, Kathy P Theall, Ave Mori, Eric Gauthier, Eustratios Bananis, Nicholas C Turner, Véronique Diéras. Long-term pooled safety analysis of palbociclib in combination with endocrine therapy for hormone receptor-positive/human epidermal growth factor receptor 2–negative advanced breast cancer: An updated analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-16.
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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 | 0.002 | 0.008 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".