Highlights
- •The prognosis of pancreatic cancer remains poor.
- •5FU has proangiogenic activity.
- •VEGFR2 might be a more effective antiangiogenic agent when combined with 5FU.
- •This study compared FOLFIRINOX to FOLFIRINOX ramucirumab (RAM).
- •FOLFIRINOX RAM was well tolerated but no survival difference.
Abstract
Background
Vascular endothelial growth factor receptor (VEGFR)-mediated signalling promotes angiogenesis
and contributes to resistance to therapy in pancreatic ductal adenocarcinoma (PDAC).
Ramucirumab (RAM) is a monoclonal antibody against VEGFR. Based on this preclinical
data, we conducted a randomised phase II trial to compare progression-free survival
(PFS) between modified FOLFIRINOX with or without RAM in first line therapy for patients
with metastatic PDAC.
Methods
This phase II randomised, multi-centre, placebo controlled, and double-blinded, trial
randomly assigned patients with recurrent/metastatic PDAC to either mFOLFIRINOX/RAM
(Arm A) or mFOLFIRINOX/placebo (Arm B). mFOLFIRINOX (oxaliplatin [85 mg/m2], irinotecan [165 mg/m2], fluorouracil [2400 mg/m2]) was received every 2 weeks, with or without RAM (8 mg/kg). The primary endpoint
is PFS at 9 months, and the secondary endpoints include overall survival (OS), response
rate and toxicity evaluation in both arms.
Results
A total of 86 subjects were enrolled, 82 were eligible (42 in Arm A versus 40 in Arm
B). The mean age was comparable (61.7 versus 63.0, respectively). Majority of the
patients were White (N = 69) and males (N = 43). The median PFS was 5.6 compared to
6.7 months, for Arm A and B, respectively. At 9 months, the PFS rates were 25.1% and
35.0% for Arms A and B, respectively (p = 0.322). The median OS in Arm A was 10.3
compared to 9.7 months for Arm B (p = 0.094). The disease response rate for Arm A
was 17.7% compared to Arm B of 22.6% and was not statistically significant. On the
univariate and multivariate analysis, there was no difference in distribution between
the two arms for age, gender, race and ethnicity. FOLFIRINOX/RAM combination was well
tolerated. Patients in Arm A reported a slightly higher number of adverse events (AEs)
compared to Arm B (589 versus 516). The most reported AE in either arm was diarrhoea
(29 versus 28), fatigue (25 versus 25), vomiting (24 versus 14), weight loss (23 versus 17),
and abdominal pain (20 versus 15). Arm A has more serious adverse events than Arm
B (43 versus 25, respectively), Sepsis was the most commonly reported in both arms
(3 in each), vomiting (3 versus 2), diarrhoea (3 versus 1) and duodenal obstruction
(3 versus 0).
Conclusions
The addition of RAM to FOLFIRINOX did not significantly impact PFS or OS. FOLFIRINOX/RAM
combination was well tolerated in the treatment of PCA. (Funded by Eli Lilly; ClinicalTrials.gov
number, NCT02581215)
Keywords
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Article info
Publication history
Published online: March 10, 2023
Accepted:
February 27,
2023
Received in revised form:
February 19,
2023
Received:
October 8,
2022
Publication stage
In Press Uncorrected ProofIdentification
Copyright
© 2023 Elsevier Ltd. All rights reserved.
