Predictors of response to CDK4/6i retrial after prior CDK4/6i failure in ER+ metastatic breast cancer Journal Article
| Authors: | Mai, N.; dos Anjos, C. H.; Razavi, P.; Safonov, A.; Patil, S.; Chen, Y.; Drago, J. Z.; Modi, S.; Bromberg, J. F.; Dang, C. T.; Liu, D.; Norton, L.; Robson, M.; Chandarlapaty, S.; Jhaveri, K. |
| Article Title: | Predictors of response to CDK4/6i retrial after prior CDK4/6i failure in ER+ metastatic breast cancer |
| Abstract: | After disease progression on endocrine therapy (ET) plus a CDK4/6 inhibitor, there is no standardized sequence for subsequent treatment lines for estrogen receptor positive (ER+) metastatic breast cancer (MBC). CDK4/6i retrial as a treatment strategy is commonplace in modern clinical practice; however, the available prospective data investigating this strategy have had inconclusive results. To frame this data in a real-world context, we performed a retrospective analysis assessing the efficacy of CDK4/6is in 195 patients who had previous exposure to CDK4/6i in a prior treatment line at our institution. Among patients who had stopped a CDK4/6i due to toxicity, CDK4/6i retrial either immediately after with a different CDK4/6i or in a further treatment line with the same initial CDK4/6i was both safe and effective, with a median time to treatment failure (TTF) of 10.1 months (95%CI, 4.8–16.9). For patients whose disease progressed on a prior CDK4/6i, we demonstrated comparable median TTFs for patients rechallenged with the same CDK4/6i (4.3 months, 95%CI 3.2–5.5) and with a different CDK4/6i (4.7 months, 95%CI 3.7–6.0) when compared to the recent PACE, PALMIRA, and MAINTAIN trials. Exploratory genomic analysis suggested that the presence of mutations known to confer CDK4/6i resistance, such as TP53 mutations, CDK4 amplifications, and RB1 or FAT1 loss of function mutations may be molecular biomarkers predictive of CDK4/6i retrial failure. © The Author(s) 2024. |
| Journal Title: | npj Breast Cancer |
| Volume: | 10 |
| ISSN: | 2374-4677 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-10-18 |
| Start Page: | 92 |
| Language: | English |
| DOI: | 10.1038/s41523-024-00699-3 |
| PROVIDER: | scopus |
| PMCID: | PMC11489574 |
| PUBMED: | 39424631 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Komal Jhaveri -- Source: Scopus |
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