Predictors of response to CDK4/6i retrial after prior CDK4/6i failure in ER+ metastatic breast cancer
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; howev...
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Veröffentlicht in: | NPJ breast cancer 2024-10, Vol.10 (1), p.92-9, Article 92 |
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Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 2374-4677 2374-4677 |
DOI: | 10.1038/s41523-024-00699-3 |