Short summary

The MONITOR-RCT is a randomized clinical trial investigating whether FDG-PET/CT can improve overall survival and quality of life in patients with newly diagnosed metastatic breast cancer by detecting disease progression earlier than standard CT. 420 patients will be enrolled from 11 sites in Denmark, Germany, and Italy. Participants will receive standard treatment, undergo FDG-PET/CT or CT scans at scheduled intervals, and complete quality-of-life questionnaires.

Rationale

Breast cancer is the most commonly diagnosed cancer in Europe and worldwide. With a continuously increasing incidence, it is estimated that by 2040, the breast cancer burden will increase to more than three million new cases per year worldwide, with more than one million breast cancer-related deaths per year (50% increase). The prognosis of breast cancer is steadily improving due to the early detection of primary cancer through screening programs and revolutionising treatment development. Despite this, approximately one-third of patients diagnosed with primary breast cancer will develop metastatic disease. In the metastatic setting, therapy improvements have made breast cancer a chronic disease with declining mortality rates, and several effective treatment lines are available for metastatic breast cancer patients today and in the future. This favourable situation requires accurate methods to assess response to treatment to achieve the most effective treatment planning. FDG-PET/CT is increasingly used in cancer staging. Several studies have shown improved sensitivity of FDG-PET/CT compared with conventional imaging for diagnosing metastatic breast cancer in retrospective and smaller prospective studies. We expect FDG-PET/CT to detect disease progression earlier than CT in patients treated for metastatic breast cancer, enabling earlier start of second-line therapies. This has the potential to increase the beneficial effect of second-line therapies at the individual level and result in a delayed need for third-line therapies, prolonged overall survival, and improved quality of life compared with patients monitored with conventional CT. Currently, no specific recommendations are provided for a diagnostic modality to monitor treatment response in patients with metastatic breast cancer. European clinical practice guidelines (ESMO) state that there is no evidence of any staging or monitoring approach for metastatic breast cancer patients that provides overall survival benefit over another approach. ESMO suggests that FDG-PET/CT might provide earlier guidance in the monitoring of bone-only or bone-predominant metastasis, but it is emphasised that prospective trials are needed to study the impact of this on treatment decisions and overall survival. This is the evidence that MONITOR-RCT will deliver. Study objectives The primary objective of the MONITOR-RCT is to demonstrate that in patients with metastatic breast cancer, response monitoring based on FDG-PET/CT is superior to response monitoring based on CT with respect to overall survival. The objective will be based on applying standardized response evaluation criteria, using an appropriate adaptation of the PERCIST criteria for FDG-PET/CT and the RECIST1.1 criteria for CT. Secondary objectives of the MONITOR-RCT are to demonstrate superiority with respect to the quality of life and exposure to oncologic treatment and to investigate the cost-effectiveness. Consequently, the primary endpoint of the study is overall survival. Secondary endpoints are quality of life, exposure to oncologic treatment, and cost-effectiveness.

Description of the cohort

Participating patients should have newly diagnosed metastatic breast cancer and be considered eligible for initiating first-line medicinal treatment and subsequent regular response monitoring.

Data and biological material

Age, gender, histopathological information about breast cancer type, time of primary diagnosis, treatment details, blood test results, PROMs (EQ-5D-5L, FACT-B). Scans and scan results (CT or FDG-PET/CT depending on randomization), scan reports, comorbidity, death/survival. Demografic data.

Collaborating researchers and departments

Department of Nuclearmedicine, Vejle

• Paw Christian Holdgaard

Department of Nuclearmedicine, Esbjerg

• Mie Holm Vilstrup

Department of Nuclearmedicine, Aalborg

• Helle Zacho

Department of Nuclearmedicine, Århus

• Mikkel Holm Vendelbo

Department of Oncology, Sønderborg

• Erik Hugger Jakobsen

Department of Oncology, Rigshospitalet

• Marie Benzon Mogensen

Department of Oncology, Herlev

• Iben Kümler

Department of Nuclearmedicine, München

• Wolfgang Weber

Department of Oncology, Bologna

• Claudio Zamagni