Journal of Clinical Oncology – Cuneo KC, Morgan MA, Sahai V, et al. |
Based on their preclinical investigations, researchers tested AZD1775 (adavosertib, an inhibitor of the Wee1 kinase) combined with gemcitabine and radiation in patients with newly diagnosed locally advanced pancreatic cancer, with focus on safety and efficacy. A total of 34 patients were administered four 21-day cycles of gemcitabine (1,000 mg/m2 days 1 and 8) with AZD1775 (once daily on days 1, 2, 8, and 9). Cycles 2 and 3 were offered concurrently with radiation, and cycles 5 to 8 were optional. Considering the rate of dose-limiting toxicities within the first 15 weeks of treatment, AZD1775 was dose-escalated employing a time-to-event continual reevaluation method. The suggested phase 2 dose of AZD1775 was 150 mg/d. For all patients, 21.7 months and 9.4 months of median overall survival and median progression-free survival, respectively, were reported. At a dose that produced target engagement in a surrogate tissue, AZD1775 in combination with gemcitabine and radiation therapy displayed good tolerability. Compared with previous results combining gemcitabine with radiation therapy, a substantially higher overall survival was reported in this study.
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