CDK4/6 inhibitors have shown tremendous improvements in outcomes for women diagnosed with advanced breast cancer when used in conjunction with endocrine therapy. The inhibitors can be added to either first or second-line endocrine therapy. The SONIA trial was initiated to find out which of the two moments to add CDK4/6 inhibitors is the best. All patients in the SONIA trial were randomly assigned to one of two groups. One group received a CDK4/6 inhibitor immediately after diagnosis of advanced breast cancer (first-line treatment). The other half received a CDK4/6 inhibitor after previous endocrine therapy had failed (i.e. second-line treatment).
The SONIA team found that the time in which the breast cancer remained under control (progression-free survival) was similar in both groups, as was the survival and quality of life. Patients who received a CDK4/6 inhibitor directly used the drug for approximately 16.5 months longer than patients who received a CDK4/6 inhibitor as second-line treatment. This significantly longer duration of CDK4/6 inhibitor treatment provided no benefit to the patients, but did result in 74% more side effects and more hospital visits.
A second-line CDK4/6 inhibitor strategy reduces 'hospital time' in a context where time is precious. As one participant put it: "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.
In addition, the longer duration of CDK4/6 inhibitor treatment associated with first-line use results in significantly higher costs to society (± €30,000 more per patient based on Dutch price levels and up to $ 5 billion in the US). The conduct and results of the SONIA study have led oncologists in the Netherlands to prescribe CDK4/6 inhibitor treatment after failure of first-line endocrine therapy. Annually, 1,700 patients in the Netherlands are eligible for CDK4/6i treatment. Implementation of the SONIA study results will therefore reduce the burden on the healthcare system, with cost reductions of over €45 million per year, while maintaining clinical efficacy.
New cancer therapies have greatly improved the outlook for many patients. However, these new therapies are associated with more side effects and higher costs. This is why research into the efficient use of drugs (e.g. shorter duration, lower dosage, less frequent administration) is crucial and holds great promise for both patients and society, as the SONIA study has shown.
Collaboration with patient advocates and the Dutch government and health insurance providers as trial funders are key success factors for the SONIA trial. Today's publication in Nature underlines the potential of this type of self-funded efficiency research. The SONIA results reaffirm the need for robust sequencing trial data to determine the optimal use of our available therapies. Importantly, this type of mostly post-marketing academic research can be very beneficial to patients and society, and should be conducted more frequently.
The SONIA study is initiated by medical oncologists Agnes Jager (Erasmus Medical Center Cancer Institute), Inge Konings (Amsterdam University Medical Centers), and Gabe Sonke (Netherlands Cancer Institute), collaborating in the Dutch Breast Cancer Research Group (BOOG).
