Elevated baseline neutrophil-to-lymphocyte ratio (NLR), a marker of subclinical inflammation, is associated with poor survival in several malignancies including mPDAC. Here we report the association of NLR with overall survival (OS) and progression-free survival (PFS) in a post-hoc analysis of the NAPOLI-1 trial (NCT01494506), that demonstrated improved survival with nal-IRI+5-FU/LV vs 5-FU/LV for treatment of mPDAC patients (pts) after disease progression following gemcitabine-based therapy.
Pts treated with nal-IRI+5-FU/LV or 5-FU/LV and available baseline NLR data were included (data cutoff: Nov 16, 2015). OS and PFS were assessed in pts with high (>5) or low (≤5) baseline NLR in individual and pooled treatment arms.
Baseline NLR was available for 221 pts: 116/117 nal-IRI+ 5-FU/LV pts and 105/105 5-FU/LV pts. In the pooled treatment arms, pts with NLR≤5 had significantly better OS compared to pts with NLR >5 (6.2 vs 3.7 months, HR = 0.7, p = 0.02). Interestingly, this improvement in OS in pts with low vs high NLR was significant in the nal-IRI+5-FU/LV arm (8.4 vs 4.3 months, HR = 0.5, p=0.001); but not in the 5-FU/LV arm (4.8 vs 3.1 months, HR = 0.9, p=0.6). Similarly, PFS was significantly higher in pts with NLR≤5 vs NLR >5 in the pooled treatment arms (2.7 vs 1.4 months, HR = 0.7, p=0.05), and the nal-IRI+5-FU/LV arm (4.2 vs 1.4 months, HR = 0.5, p=0.002), but not the 5-FU/LV arm (1.5 vs 1.4 months, HR = 1.1, p=0.6).Table:
|Pooled treatment arms||nal-IRI + 5FU/LV||5FU/LV|
|(n = 155)||(n = 66)||(n = 82)||(n = 34)||(n = 73)||(n = 32)|
|Median1 OS, months (95% CI)||6.2 (5.2 - 7.6)||3.7 (3.1 - 4.4)||8.4 (6.1 - 10.2)||4.3 (3.4 - 4.7)||4.8 (3.6 - 6.1)||3.1 (1.9 - 4.2)|
|95% CI||0.5 - 0.9||0.3 - 0.8||0.6 - 1.4|
|Median1 PFS, months (95% CI)||2.7 (2.4 - 3.3)||1.4 (1.4 - 1.6)||4.2 (3.1 - 5.6)||1.4 (1.4 - 2.8)||1.5 (1.4 - 2.6)||1.4 (1.3 - 1.9)|
|95% CI||0.5 - 1.0||0.3 - 0.8||0.8 - 1.8|
Medians reflect Kaplan-Meier estimates2
Hazard ratios (HRs) reflect Cox regression analysis.3
Two-sided p-value < 0.05 considered statistically significant in these exploratory analyses
Data from these exploratory analyses are consistent with previous reports on the prognostic value of baseline NLR in mPDAC, and extend it to the post-gemcitabine setting. Median OS and PFS were improved in pts with low vs high baseline NLR in the nal-IRI+5-FU/LV arm but not in the 5-FU/LV arm. Clinical implications of these data remain to be determined.
Clinical trial identification
Legal entity responsible for the study
Merrimack Pharmaceuticals, Inc.
Ipsen Biopharmaceuticals, Inc.
R.A. Hubner: Consulting for Celgene, BTQ, Baxalta. Speakers’ Bureau for Abbott, Ipsen. L-T. Chen: Consulting for ONO, Eli Lilly, MSD, PharmaEngine, Merrimack, TTY, Syncore, Five Prime, Novartis. Research funding from Novartis, GSK, TTY, Polaris. G. Bodoky: Honoraria from Servier, Roche, Bayer, Pfizer, Janssen, Novartis, Lilly. Advisory board of Bayer, Roche, Pfizer, Janssen, Novartis, Lilly, Taiho, Nordic. D. Cunningham: Research funding from Amgen, Astrazeneca, Bayer, Celgene, Merrimack, Medimmune, Merck Serono, Sanofi. J.T. Siveke: Research funding from Celgene, BMS, 4SC, Novartis, Boehringer. Consultant for Merrimack, Baxalta, Celgene, Eli Lilly. F.S. Braiteh: Consulting and speaking fees from Ipsen. F.A. de Jong: Employee and stockholder of Shire. B. Belanger, R. Walls, P.D. Mody: Employee of Ipsen Biopharmaceuticals, Inc. D.D. von Hoff: Research funding from Merrimack. A. Wang-Gillam: Research funding from Newlink, Astrazeneca, Biomed Valley, Eli Lilly, Abbvie, Verastem, Precision Biologics. Consulting for Merrimack, Pfizer, Newlink. All other authors have declared no conflicts of interest.