Randomised, phase II study of selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer
Authors
Doherty, M. K.Tam, V. C.
McNamara, Mairead G
Jang, R.
Hedley, D.
Chen, E.
Dhani, N.
Tang, P.
Sim, H. W.
O'Kane, G. M.
DeLuca, S.
Wang, L.
Pedutem, T.
Knox, J. J.
Affiliation
Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, CanadaIssue Date
2022
Metadata
Show full item recordAbstract
Introduction: Cisplatin and gemcitabine (CisGem) are standard chemotherapy for advanced biliary tract cancer (BTC). The MEK inhibitor selumetinib showed synergy with gemcitabine when administered sequentially in BTC. This randomised 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 75 mg BID but amended to 50 mg BID due to toxicity. Results: In all, 51 participants were evaluable for response. No significant difference was seen in mean change in tumour size at 10 weeks between arms A and C (-7.8% vs -12.8%, P = 0.54) or arms 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.Citation
Doherty MK, Tam VC, McNamara MG, Jang R, Hedley D, Chen E, et al. Randomised, Phase II study of selumetinib, an oral inhibitor of MEK, in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer. British journal of cancer. 2022 Jul 22. PubMed PMID: 35869145. Epub 2022/07/23. eng.Journal
British Journal of CancerDOI
10.1038/s41416-022-01903-6PubMed ID
35869145Additional Links
https://dx.doi.org/10.1038/s41416-022-01903-6Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41416-022-01903-6