| Autor: |
Mai N; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Dos Anjos CH; Oncology Service, Department of Medicine, Hospital Sirio-Libanes, Sao Paulo, SP, Brazil., Razavi P; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Safonov A; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Patil S; Department of Quantitative Health Sciences, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio., Chen Y; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York., Drago JZ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Modi S; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Bromberg JF; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Dang CT; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Liu D; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Norton L; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Robson M; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Chandarlapaty S; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Jhaveri K; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. |
| Abstrakt: |
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. |
