Randomized, Phase II Study of Selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer.

Introduction
Cisplatin and gemcitabine (CisGem) is standard chemotherapy for advanced biliary tract cancer (BTC). The MEK inhibitor selumetinib showed synergy with gemcitabine when administered sequentially in BTC. This randomized phase 2 trial aimed to assess the efficacy of sequential or continuous selumetinib with CisGem.
Methods
Patients with advanced BTC received CisGem; arm A included selumetinib every day, arm B: selumetinib, days 1-5, 8-19 each cycle. Arm C received CisGem alone. Selumetinib was dosed at 75mg BID but amended to 50mg BID due to toxicity.
Results
51 participants were evaluable for response. No significant difference was seen in mean change in tumor size at 10 weeks between Arm A and C (-7.8% vs -12.8%, p=0.54) or arm B and C (-15% vs -12.8%, p=0.78). There was no difference in median progression-free survival (6.0, 7.0, 6.3 months, p>0.95) or overall survival (11.7, 11.7, 12.8 months, p=0.70) for arms A, B and C, respectively. More participants experienced grade 3-4 toxicities in selumetinib-containing arms. More participants in arm A required chemotherapy dose reductions (p=0.01) with lower chemotherapy dose intensity during the first 10 weeks.
Conclusion
Adding sequential or continuous selumetinib to CisGem failed to improve efficacy and increased toxicity in patients with advanced BTC.