Results
Baseline characteristics
This study included 167 patients who received anti-PD1 treatment with
pembrolizumab after failure of first-line chemotherapy. The clinical
characteristics of the patients and relations with response on the first
CT scan are summarized in Table 1. The mean age was 60.2 ±6.8 years;
most of the patients were men (64%), and almost all patients exhibited
an ECOG PS of 1 (98%). The lung was the most common metastatic site
(73%), followed by pleural effusion (59%) and bone (40%). All
patients were eligible for the examination of tumor PD-L1 expression, of
which 13 patients (7.8%) had expression in more than 50%, 80 patients
(47.9%) had expression in 25-49%, and 74 patients (44.3%) had
expression in 1-24%. Of all the clinicopathological characteristics of
the patients, only NLR2, PLR2 and the presence of sarcopenia were
significantly related to the response on the first CT scan (Table 1).
Hematological biomarkers and their relation to response on
the first CT scan
On the first CT scan after chemotherapy treatment, 15 (8.9%) patients
showed progressive disease. After treatment with pembrolizumab on the
first CT scan evaluation, these 15 patients were subdivided as follows:
8 hyperprogressors (HPs), 1 pseudoprogressor (PP) and 6 nonprogressors
(NPs). These 15 patients had significantly higher NLR1 and PLR1 than the
patients without progressive disease (7.49±2.8 vs 4.31±2.45; 283.3±96.5
vs 207±102.6, respectively). Twelve of them had an NLR>5,
and at least 9 (∆PMMA was not available for 3) of them had ∆PMMA≥10%.
On the first CT scan after immunotherapy treatment, 45 (26.9%) patients
showed progressive disease, and at least 25 (∆PMMA was not available for
7) of them had ∆PMMA≥10%. Of them, 16 patients (9.6%) were classified
as HPs, 5 (2.9%) were classified as PPs, and the remaining 24 (14%)
were classified as Ps. Patients with pseudoprogression were without any
clinical deterioration and received further treatment with immunotherapy
for another 8 weeks, when the control CT scan proved a partial response
for 3 patients and stable disease for 2 patients; the response lasted
for at least 6 months. Of all HPs, 15 (93%) had an NLR>5.
HPs had higher mean values of NLR2, PLR2 and ∆NLR, but not higher ∆PLR
values, than Ps or NPs (Table 2). There was no significant difference in
hematological parameters between HPs and PPs, Ps and NPs, Ps and PPs, or
NPs and PPs, except for NLR2, for which NPs had significantly lower
values than PPs (Table 2).
ROC analysis was performed to explore the potential predictive role of
these biomarkers, NLR2, PLR2, ΔNLR, and ΔPLR, as noninvasive biomarkers
for discrimination between patients with or without HPD (Table 3). At
the optimal cutoff values for NLR2, the biomarker could significantly
and well distinguish between patients with or without HPD (AUC = 0.85,
95% CI: 0.75- 0.95, p < 0.001) with a sensitivity of 87.5%
and a specificity of 68.9%. PLR2 also allowed significant but fair
discrimination between patients with and without HPD (AUC = 0.79, 95%
CI: 0.66- 0.92, p < 0.001) with a sensitivity of 75.0% and a
specificity of 64.1% (Figure 1A and B). ΔNLR could also discriminate
between patients with and without HPD, but poorly (Table 3). The
Wilcoxon test showed that the ALC and APC did not change significantly
from chemotherapy. Nevertheless, the ANC significantly differed between
the first cycle of chemotherapy and the first pembrolizumab infusion.
The McNemar test showed that the proportion of patients with an
NLR>5 and a high PLR did not change significantly with
chemotherapy treatment.
A significantly strong correlation was detected between NLR1 and PLR1
(rho=0.763) and NLR2 and PLR2 (rho=0.785), and a moderate correlation
was detected between ΔNLR and ΔPLR (rho=0.465).