A phase 1b trial defined the recommended phase 2 dose of nab-paclitaxel (150 mg/m2) in combination with cisplatin, capecitabine, and gemcitabine (800, 30, and 1250 mg/m2 every 2 weeks, respectively; PAXG regimen). A randomized phase 2 trial of PAXG or nab-paclitaxel-gemcitabine (AG) was performed (NCT01730222).
Chemo-naive patients with 18-75 years, pathologic diagnosis of unresectable or borderline resectable pancreatic adenocarcinoma (NCCN definition), Karnofsky Performance Status ≥ 70 were eligible for the study. The primary endpoint was resectability rate. According to A' Hern design (p0 = 5%; p1 = 20%; α = 0.05; power = 80%), the total number of patients to enrol in each arm was 27. With ≥ 4 of 27 eligible patients resected, each regimen will be considered active.
Between Apr 2014 and Feb 2016, 54 patients (table 1) were randomized at a single Institution to receive PAXG (arm A; N = 26) or AG (arm B; N = 28). Resection after 4-6 cycles of chemotherapy was performed only in initially borderline resectable patients (5 arm A; 5 R0; 4 N0; 5 arm B; 5 R0; 1 N0). One arm A and 2 arm B patients were deemed resectable and are waiting for surgery. Treatment is ongoing in 4 patients. Main grade 3/4 toxicity was (A/B): neutropenia 76/57%; thrombocytopenia 5/9%; fatigue 10/26%; neuropathy 0/22%; diarrhea 5/13%; nausea 5/13%; serious adverse events 22/29%. A partial response was observed in (A/B) 50/32% and stable disease in 50/61% patients. CA19-9 decreased by > 49% in 95/86%; >89% in 36/19% patients with elevated basal value. Progression was observed in 7 arm A and 17 arm B patients: PFS-6 (A/B) was 100%/61%.
|KPS||90-100||19 (73%)||24 (86%)|
|70-80||7 (27%)||4 (14%)|
|Unresectable||16 (62%)||13 (46%)|
|Borderline||10 (38%)||15 (54%)|
|Head||18 (69%)||20 (71%)|
|CA19.9||>ULN||22 (85%)||21 (75%)|
Both AG and PAXG regimens reached the primary endpoint. Preliminary results suggest that the addition of cisplatin and capecitabine to AG backbone is feasible and seems to improve disease control. The PAXG regimen warrant further exploration in this setting of patients.
Clinical trial identification
Legal entity responsible for the study
IRCCS San Raffaele, Milan, Italy
M. Reni: Advisory role: Celgene, Boehringer Ingelheim, Genentech, Lilly, Merck Serono, Baxalta, Pfizer, Novocure, Halozyme. All other authors have declared no conflicts of interest.