Time for a comeback.

Top Line: Wee1? Wait, after LAP-07 we thought WeeLost.

The Study: Wee1 is a kinase that is involved in regulating cell cycle progression. Preclinical evidence suggests that it’s inhibition may lead to both chemo- and radio-sensitization in pancreatic cancer cells. So, where best to try it? Yep, with chemoradiation for locally advanced pancreatic cancer. In this phase 1 study, adavosertib, a small molecule inhibitor of Wee1 (what, were you expecting a large molecule?) was administered along with gemcitabine and radiation in patients with locally advanced pancreatic cancer in search of a maximally tolerated dose. Radiation consisted of 2.1 Gy x 25 = 52.5 Gy to the tumor and involved nodes using IMRT. As you can tell, this trial doesn’t exactly fit into the treatment paradigm most of us are seeing for locally advanced pancreatic cancer, namely several months of multi-agent chemo and then consideration of consolidation. But anything to help radiation’s chances in the pancreatic cancer world are welcome. Among the 34 enrolled patients, a quarter had dose limiting toxicity in the form of anorexia and nausea. Outcomes were encouraging with a median overall survival of 22 months and median progression free survival of 9 months. Even though Wee1 this study, it’s gonna take an uphill climb and randomized data to get chemoradiation back in the game for locally advanced pancreatic cancer.

TBL: The Wee1 kinase-inhibitor adavosertib is tolerable and may enhance the efficacy of concurrent gemcitabine and radiation for locally advanced pancreatic cancer. | Cuneo, J Clin Oncol 2019