Discussion
pneumonitis, nausea/vomiting, fatigue, diarrhea, cancer death, PDAC, deaths, all-grade
PNEUMONITIS, PANCREATIC DUCTAL ADENOCARCINOMA, ADVERSE EVENTS
Pancreatic ductal adenocarcinoma (PDAC) is predicted to be the second leading cause of cancer death after 2030, and there are projected to be 62 210 new diagnoses and 49 830 deaths in the US in 2022.Greater than 95% of PDAC carries the KRAS oncogene which results in a constitutive activation of the 3-tiered RAF-MEK-ERK mitogen-activated protein kinase (MAPK) cascade.A total of 18 patients were enrolled into 2 parts: dose de-escalation and dose expansion. In dose de-escalation, 10 enrolled patients received ulixertinib monotherapy (600 mg BID) for 2 weeks. Seven patients continued on the triplet with ulixertinib 600 mg BID. In dose expansion, after 2 patients began treatment on triplet and withdrew. In response, ulixertinib was adjusted from 600mg BID to 450 mg BID as RP2D, and 6 more patients were enrolled. For 15 patients treated with the triplet, overall grade ≥ 3 TRAEs of the triplet were similar to standard GnP. One patient died from pneumonitis possibly related to gemcitabine. The high frequency of all-grade TRAE from the triplet, especially fatigue, nausea/vomiting and diarrhea, led to patient withdrawals, ultimately leading to premature study termination (Triplet regimen treatment related adverse events (TRAE) of enrolled patients (Treatment course of all 18 enrolled patients. 15 patients received ulixertinib plus GnP.