Phase 1 Study of Palbociclib with Cisplatin or Carboplatin in the Management of Patients with Advanced Pancreatic Cancer

Background Addition of agents targeting critical signal mediators of cancer cell proliferation such as cyclin-dependent kinases (CDK) potentiates the efficacy of platinum chemotherapy. Patients and Methods Patients with any advanced cancer after at least one prior therapy were enrolled on dose escalation to determine recommended phase II doses (RP2D). Expansion cohorts were then opened for pancreaticobiliary tract (PBT) cancers. Primary endpoint was objective response rate (ORR). Secondary endpoints included safety, overall survival (OS), progression free survival (PFS). Results We enrolled 39 patients on dose escalation and 32 additional patients on dose expansion. RP2D of Palbociclib 100 mg on D2-22 + cis 60 mg/m2 IV on D1 Q4W (Arm A); and Palbociclib 75 mg on D2-22 + carbo AUC 6 IV on D1 Q4W (Arm B). ORR for Part I were 12.5% (Arm A) and 25% (Arm B). Median PFS and OS for dose expansion were 2.1 and 4.9 month respectively. For PDAC, mPFS was 1.9 months (95% CI: 1.7, 2.4) and OS was 3.7 months (95% CI: 2.7, 5.7). Most common treatment related adverse events (TRAEs—all grade %): Arm A—neutropenia (66%), thrombocytopenia (26%), nausea, fatigue and anemia (20% each); Arm B– neutropenia (64.7%), thrombocytopenia (53%) and anemia (29%). There was no grade 4-5 TRAEs. Conclusions Palbociclib with cisplatin or carboplatin had an acceptable safety profile and clinical responses in some treatment refractory advanced cancers. There was no objective response, but about half of PDAC patients had disease stabilization. Additional efforts are needed to exploit CDK abnormalities in these patients. Clinical trial information NCT02897375