Procedures
MSI, death, Tumour, toxicity, tumour
DISEASE PROGRESSION, TUMOUR, ADVERSE EVENTS, DISEASE, MICROSATELLITE INSTABILITY, CPS, TUMOUR, ONCOLOGY
Patients received intravenous durvalumab at a fixed dose of 1500 mg over a 4-week (Q4W) cycle for up to 13 cycles and intravenous tremelimumab at a fixed dose of 75 mg Q4W for up to four cycles. Treatment was administered until the completion of the treatment schedule (i.e. 12 months), confirmed progression of the disease, unacceptable toxicity, patient withdrawal or death; whichever occurred first. Dose reductions were not permitted, although doses could be delayed for up to 12 weeks due to toxicity. Patients could be retreated with durvalumab and tremelimumab in case of progression after completing the 4 cycles of durvalumab plus tremelimumab combination or at the end of the study treatment as scheduled while maintaining clinical benefit, according to the investigator´s criteria.Clinical assessments included medical history review; complete physical examination, including Eastern Cooperative Oncology Group Performance Status (ECOG PS), vital signs, height and weight; laboratory tests and urinalysis; record of adverse events (AEs); treatment compliance; and tumour marker assessments. Tumour imaging assessments by computed tomography (CT) or magnetic resonance imaging (MRI) scan at baseline, and every 12 weeks (±1 week) until disease progression or the initiation of an alternative treatment. CT or MRI scans were assessed locally by investigators following both, RECIST 1.1 and irRECIST 1.1 criteria. Histology (only cohort 4) and PD-L1 expression in archival formalin-fixed tumour samples was independently assessed by a central laboratory. PD-L1 combined positive score (CPS) was assessed using the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA). PD-L1 antibody was from Roche (Cat n°: 741-4905). PD-L1 CPS of 1 or greater was considered positive. Central revision of microsatellite instability (MSI) phenotype by IHC was performed for patients who had a response. MSI phenotype diagnosis followed ESMO recommendations: loss of nuclear expression of at least one out of four proteins in IHC test performed using regular MLH1 (Roche, cat n°: 760-5091), MSH6 (Roche, cat n°: 760-5092), PMS2 (Roche, cat n°: 760-5094), MSH2 (Roche, cat n°: 760-5093) antibodies.