Abstract PO5-04-11: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) beyond progression in hormone receptor positive advanced breast cancer: a systematic review and meta-analysis
Bibliographic record
Abstract
Abstract Introduction The use of CDK 4/6i (palbociclib/ribociclib/abemaciclib) with endocrine therapy (ET) is a widely adopted first line standard treatment for hormone receptor positive advanced breast cancer (HR+ABC). Data supporting incorporation of CDK 4/6i ± ET beyond progression are less clear. Recent studies have evaluated either the continuation of or switching to a different CDK 4/6i, with a change in ET after progression on 1st line CDK4/6i with varying results. A pooled analysis of this strategy could be useful for clinical decision making. Methods We reviewed reports of both observational and clinical studies that evaluated continuing the same CDK4/6i or switching to a different agent after progression on first line CDK4/6i with ET. The search included the grey literature without exclusions for publication year or language. The mean overall response rate (ORR), clinical benefit rate (CBR) and progression free survival (PFS) weighted by study sample size were calculated. Meta-regression comprising linear regression weighted by sample size (mixed effects) was performed to explore the association between disease and treatment-related factors and benefit from continuing a CDK4/6i. Quantitative significance was assessed using the Burnand criteria. Analyses were performed using SPSS version 28 (IBM Corp, Armonk NY). Results Thirteen studies (N=1006 patients) were included; 7 were prospective trials and 2 cohorts of the same retrospective study included separately). Study patients had a median age of 57.8 years and 66% had visceral metastases. Among patients whose type of first-line CDK 4/6i exposure was reported (84.5%), 81.21% received Palbociclib 3.28% received Ribociclib and 0.89% received Abemaciclib. Six patients received both Palbociclib and Ribociclib. The median duration of first line CDK 4/6i therapy was 13.8 months. In the second line,the mean ORR was 12.8%, CBR 38.8%, and median PFS was 4.6 months. The ORRs for Palbociclib, Ribociclib and Abemaciclib, irrespective of type of prior CDK 4/6i, were 7.3%, 14.7% and 18.6%, respectively. The CBR for Palbociclib, Ribociclib and Abemaciclib were 33.1%, 42.2% and 46.8%, respectively. The median PFS based the CDK 4/6i used in second line was 4.2 (Palbociclib), 5.5 (Ribociclib) and 9.2 (Abemaciclib) months. Meta-regression analysis of PFS is included in the table. Conclusion Continuing a CDK 4/6i± ET beyond progression yields modest benefits. Switching CDK4/6i offers slightly better ORR and PFS. Continuing Palbociclib beyond progression does not seem beneficial. Longer duration of CDK4i exposure in the first line appears to be associated with shorter PFS in the second line. Small number of studies with limited number of patients likely affect results. Meta-regression analysis of PFS of CDK 4/6i with or without ET in subsequent line of therapy. Citation Format: Neha Pathak, Sudhir Kumar, Diego Malon Gimenez, Massimo Di Iorio, Consolacion Molto Valiente, Danielle Cuthbert, Meredith Li, Atul Batra, Michelle Nadler, Eitan Amir, Abhenil Mittal. Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) beyond progression in hormone receptor positive advanced breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-11.
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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 | 0.012 | 0.023 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.014 | 0.026 |
| Bibliometrics | 0.006 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 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".