Abstract OT3-04-03: KEYNOTE-756: A randomized, double-blind, phase III study of pembrolizumab versus placebo in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk early-stage ER+/HER2– breast cancer
Bibliographic record
Abstract
Abstract Background:Although ER+/HER2– breast cancer has a better overall prognosis than other breast cancer subtypes, there is a high-risk subpopulation characterized by high-grade tumors and decreased sensitivity to endocrine therapy, higher responsiveness to chemotherapy and worse prognosis. A large meta-analysis of prospective studies focusing on neoadjuvant chemotherapy (NAC) for treatment of stage I-III breast cancer demonstrated that increased pathologic complete response (pCR) rates at surgery were associated with improved survival. This correlation was observed across triple-negative breast cancer (TNBC), HER2+ breast cancer, and high-grade HR+/HER2- breast cancer. Specifically, patients with a pCR after NAC had a 5-year event-free survival (EFS) rate of 90%, whereas patients who did not achieve a pCR had a 5-year EFS rate of 60%.Therefore, increasing pCR rates after NAC may have a substantial impact for patients with high-risk early-stage HR+/HER2– breast cancer. KEYNOTE-756 is a global, randomized, double-blind, phase III study of pembrolizumab (vs placebo) + chemotherapy as neoadjuvant treatment, followed by pembrolizumab (vs placebo) plus endocrine therapy as adjuvant treatment for patients with high-risk, early-stage ER+/HER2– breast cancer. Methods: Patients with T1c-2 cN1-2 or T3-4 cN0-2 grade 3 or grade 2 with Ki-67 ≥30%, invasive, ductal ER+/HER2– breast cancerwill be stratified by lymph node involvement (positive vs negative), tumor PD-L1 status (positive vs negative), ER positivity (≥10% vs <10%), and anthracycline dosing schedule (Q3W vs Q2W), and then randomized 1:1 to receive neoadjuvant treatment with pembrolizumab 200 mg Q3W or placebo in combination with paclitaxel (80 mg/m2 QW) for 4 cycles followed by (doxorubicin [60 mg/m2] or epirubicin [100 mg/m2]) plus cyclophosphamide (600 mg/m2) Q2/3W for another 4 cycles. After definitive surgery (± radiation therapy, as indicated), patients will receive adjuvant treatment with pembrolizumab (200 mg Q3W) or placebo for 9 additional administrations, in combination with endocrine therapy, which can be given for up to 10 years. Co-primary end points are pCR rate and EFS. Secondary end points are safety and overall survival. The global study will open in North America and Latin America, Europe, and Asia Pacific in the second half of 2018. Citation Format: Cardoso F, Bardia A, Andre F, Cescon DW, McArthur H, Telli M, Loi S, Cortés J, Schmid P, Harbeck N, Denkert C, Jackisch C, Jia L, Tryfonidis K, Karantza V. KEYNOTE-756: A randomized, double-blind, phase III study of pembrolizumab versus placebo in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk early-stage ER+/HER2– breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-04-03.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.004 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.011 | 0.002 |
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".