An innovative Dutch breast cancer research project, the SONIA trial, published in Nature, demonstrates that delaying and shortening the duration of CDK4/6 inhibitor therapy in patients with hormone receptor-positive advanced breast cancer yields similar survival outcomes while significantly reducing toxicity and costs.
The SONIA trial compared the immediate use of CDK4/6 inhibitors with their use after the failure of initial endocrine therapy. Patients were randomized into two groups: one receiving a CDK4/6 inhibitor immediately after diagnosis of advanced breast cancer (first-line), and the other receiving it after previous endocrine therapy failed (second-line).
The study found that progression-free survival, overall survival, and quality of life were similar in both groups. However, patients receiving CDK4/6 inhibitors in the first-line setting used the drugs for approximately 16.5 months longer, resulting in 74% more side effects and increased hospital visits without any added clinical benefit.
According to the study, the longer duration of CDK4/6 inhibitor treatment in the first-line strategy leads to significantly higher societal costs, estimated at approximately €30,000 more per patient in the Netherlands and up to $5 billion in the US. The trial has influenced oncologists in the Netherlands to prescribe CDK4/6 inhibitors after the failure of first-line endocrine therapy. With approximately 1,700 patients in the Netherlands eligible for CDK4/6 treatment annually, implementing the SONIA study results could reduce healthcare system burden by over €45 million per year while maintaining clinical efficacy.
One participant noted the improved quality of life on endocrine therapy without CDK4/6 inhibitors, stating, "I am currently on endocrine therapy without CDK4/6 inhibitor treatment. I have no toxicity and I can work full time, which has a positive impact on my quality of life."
The SONIA study highlights the importance of efficiency research in drug utilization, such as shorter durations, lower dosages, and less frequent administration, to balance improved patient outcomes with reduced side effects and costs. The trial was a collaborative effort involving patient advocates, the Dutch government, and health insurance providers. The SONIA results emphasize the need for robust sequencing trial data to optimize the use of available therapies and advocate for more post-marketing academic research to benefit patients and society.
The SONIA study was initiated by medical oncologists Agnes Jager (Erasmus Medical Center Cancer Institute), Inge Konings (Amsterdam University Medical Centers), and Gabe Sonke (Netherlands Cancer Institute), in collaboration with the Dutch Breast Cancer Research Group (BOOG).
