Endpoints and assessments
death, Pain, SD, pain, PD, tumour, Tumours, Cancer
ADVERSE EVENT, BONE LESIONS, DISEASE, TUMOUR, CANCER
The primary endpoint was PFS per independent review, defined as the time from randomisation until progressive disease (PD) according to RECIST v1.1 or death from any cause.Secondary endpoints were: overall survival (OS; time from randomisation to death from any cause), disease control (best overall response of either complete response [CR], partial response [PR], stable disease [SD] or non-CR/non-PD; SD and non-CR/non-PD must have been observed until at least the Week 24 tumour assessment), duration of disease control, objective response (defined as best overall response of CR or PR), and time to pain progression or increase in pain treatment.Tumours were assessed by computed tomography (CT) scans of the chest, abdomen and pelvis, a brain CT or magnetic resonance imaging, and a bone scan at baseline. If bone lesions were already known or confirmed at screening, bone scans had to be performed with every other CT scan and with an additional bone scan at Week 8. Assessments were performed every 8 weeks up to Week 80 (and every 12 weeks thereafter).Tumour response and progression was evaluated per RECIST v1.1 in combination with MD Anderson criteria for patients with target and/or non-target bone lesions [Increases in pain treatment were measured based on the Analgesic Quantification Algorithm (AQA) and pain was measured with the Brief Pain Inventory – Short Form (BPI–SF). The BPI-SF is a nine-item, self-administered questionnaire to evaluate the severity of pain and its impact on daily functioning using a 10-point scale. A difference of two points is considered clinically meaningful [Time to pain progression or increase in pain treatment was defined as the time from randomisation until the earliest of: a ≥ 2 point increase from baseline in the BPI-SF item 3 (worst pain), without a decrease (of ≥ 1 point) from baseline analgesics use (via the AQA), or a ≥ 2 point increase from baseline in the ADA, or death. Safety was assessed by the incidence and severity of AEs, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.