Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers
Journal of Clinical Investigation Dec 18, 2021
Yarchoan M, Cope L, Ruggieri AN, et al. - In biliary tract cancer (BTC) cases, a prolonged progression-free survival (PFS) is conferred by the combination of atezolizumab plus cobimetinib vs atezolizumab monotherapy, but in both arms, low response rate was observed which highlights the immune-resistant nature of BTCs.
In this open-label phase II study, 77 patients with BTC were randomized to atezolizumab (anti–programmed death ligand 1) as monotherapy or in combination with cobimetinib (mitogen/extracellular signal–regulated kinase inhibitor).
Primary endpoint was achieved, with a median PFS of 3.65 months in the combination arm vs 1.87 months in the monotherapy arm (HR 0.58).
A partial response was seen in one patient in the combination arm (3.3%) and 1 patient in the monotherapy arm (2.8%).
More rash, gastrointestinal events, CPK elevations, and thrombocytopenia occurred with combination therapy.
In exploratory analysis of tumor biopsies, combination therapy was associated with enhanced expression of antigen processing and presentation genes and an increase in CD8/FoxP3 ratios.
Greater clinical benefit from the combination was evident in patients with higher baseline or lower fold changes in expression of certain inhibitory ligands (LAG3, BTLA, VISTA) on circulating T cells.
Exclusive Write-ups & Webinars by KOLs
Daily Quiz by specialty
Paid Market Research Surveys
Case discussions, News & Journals' summaries