Investigating the treatment of metastatic breast cancer : real-world evidence on treatment patterns, safety and efficacy

Sammanfattning: Metastatic breast cancer is an incurable disease causing a spectrum of symptoms and leading to a continuous deterioration of performance status and quality of life. It is a heterogeneous disease, with survival being related to tumor biology and patient-related factors. Treatment of metastatic breast cancer aims at preventing cancer growth, relieving symptoms, improving quality of life and prolonging survival, and is most commonly given continuously. The choice of treatment depends on tumor subtype, performance status, organ function and comorbidities. Real world studies describe the effectiveness and safety of different therapies as well as treatment patterns in routine clinical practice, and can provide valuable information on the treatment of populations not often enrolled in randomized clinical trials. The aim of this thesis was to examine how metastatic breast cancer is treated in the real-world setting, with focus on treatment patterns as well as safety and efficacy of specific agents. Eribulin is a non-taxane microtubule inhibitor approved for the treatment of metastatic breast cancer after progression on at least two prior chemotherapy lines, including anthracyclines and taxanes. In Paper I, patients treated with eribulin were evaluated regarding efficacy and safety using data from electronic health records. The results confirmed that eribulin was safe and well tolerated, with a clinical benefit seen in half of the patients. No differences in treatment benefit were seen across histopathologic subgroups. With the aim of investigating treatment with chemotherapy near the end of life in metastatic breast cancer patients, data were collected from the Stockholm Gotland Breast Cancer Register as well as from electronic health records in Sweden and Greece for Paper II. Chemotherapy use near the end of life was common in both populations. Both orally and intravenously administered regimens were used. In the Swedish cohort, age and albumin levels were associated with the use of futile chemotherapy, with chemotherapy near the end of life being more commonly administered to younger patients. Several studies have shown a survival benefit for metastatic breast cancer patients treated with cyclin dependent kinase 4/6 inhibitors in combination with endocrine treatment. In Paper III, patients treated with cyclin dependent kinase 4/6 inhibitors were assessed regarding efficacy and safety using data from electronic health records. The treatment was well tolerated, with no new safety signals. However, there was a higher rate of treatment discontinuations than reported in randomized clinical trials. The efficacy of cyclin dependent kinase 4/6 inhibitors was significantly impaired in heavily pretreated patients. In Paper IV, data were collected from the Stockholm Gotland Breast Cancer Register as well as from electronic health records in order to investigate patients with short survival time after metastatic breast cancer diagnosis. One out of six patients with metastatic breast cancer survived less than three months following diagnosis, and out of those, nearly half did not receive any antitumor treatment. Patients with short survival time were older and had more aggressive tumor characteristics and metastatic patterns. Current treatment guidelines recommend that patients with newly diagnosed hormone receptor positive/human epidermal growth factor receptor 2 negative metastatic breast cancer are treated with endocrine therapy with or without cyclin dependent kinase 4/6 inhibitors, unless presenting with a visceral crisis. In Paper V, with the use of data from the Stockholm Gotland Breast Cancer Register and the Swedish Prescribed Drug Register, we aimed to investigate how patients with hormone receptor positive metastatic breast cancer are treated in the first line setting. Nearly half of the patients received chemotherapy, in non-adherence to guidelines. A significantly worse survival was seen in patients treated with chemotherapy, even after adjusting for menopausal status, first metastatic site and distant recurrence free interval. In summary, treatment with eribulin as well as with cyclin dependent kinase 4/6 inhibitors in routine clinical practice was safe, with greater treatment benefit seen in earlier treatment lines. Treatment of patients with first line chemotherapy instead of endocrine treatment was common. Also, use of chemotherapy treatment near the end of life was fairly common, especially in younger patients in the Swedish study population.